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Sample records for genotype relative risks

  1. How to Relate Complex DNA Repair Genotypes to Pathway Function and, Ultimately, Health Risk

    Energy Technology Data Exchange (ETDEWEB)

    Jones, IM

    2002-01-09

    Exposure to ionizing radiation increases the incidence of cancer. However, predicting which individuals are at most risk from radiation exposure is a distant goal. Predictive ability is needed to guide policies that regulate radiation exposure and ensure that medical treatments have maximum benefit and minimum risk. Differences between people in susceptibility to radiation are largely based on their genotype, the genes inherited from their parents. Among the important genes are those that produce proteins that repair DNA damaged by radiation. Base Excision Repair (BER) proteins repair single strand breaks and oxidized bases in DNA. Double Strand Break Repair proteins repair broken chromosomes. Using technologies and information from the Human Genome Project, we have previously determined that the DNA sequence of DNA repair genes varies within the human population. An average of 3-4 different variants were found that affect the protein for each of 37 genes studied. The average frequency of these variants is 5%. Given the many genes in each DNA repair pathway and their many variants, technical ability to determine an individual's repair genotype greatly exceeds ability to interpret the information. A long-term goal is to relate DNA repair genotypes to health risk from radiation. This study focused on the BER pathway. The BER genes are known, variants of the genes have been identified at LLNL, and LLNL had recently developed an assay for BER function using white blood cells. The goal of this initial effort was to begin developing data that could be used to test the hypothesis that many different genotypes have similar DNA repair capacity phenotypes (function). Relationships between genotype and phenotype could then be used to group genotypes with similar function and ultimately test the association of groups of genotypes with health risk from radiation. Genotypes with reduced repair function are expected to increase risk of radiation-induced health effects. The

  2. Interleukin-6-related genotypes, body mass index, and risk of multiple myeloma and plasmacytoma.

    Science.gov (United States)

    Cozen, Wendy; Gebregziabher, Mulugeta; Conti, David V; Van Den Berg, David J; Coetzee, Gerhard A; Wang, Sophia S; Rothman, Nathaniel; Bernstein, Leslie; Hartge, Patricia; Morhbacher, Ann; Coetzee, Simon G; Salam, Muhammad T; Wang, Wei; Zadnick, John; Ingles, Sue A

    2006-11-01

    Interleukin-6 (IL-6) promotes normal plasma cell development and proliferation of myeloma cells in culture. We evaluated IL-6 genotypes and body mass index (BMI) in a case-control study of multiple myeloma and plasmacytoma. DNA samples and questionnaires were obtained from incident cases of multiple myeloma (n = 134) and plasmacytoma (n = 16; plasma cell neoplasms) ascertained from the Los Angeles County population-based cancer registry and from siblings or cousins of cases (family controls, n = 112) and population controls (n = 126). Genotypes evaluated included IL-6 promoter gene single nucleotide polymorphisms (SNP) at positions -174, -572, and -597; one variable number of tandem repeats (-373 A(n)T(n)); and one SNP in the IL-6 receptor (IL-6ralpha) gene at position -358. The variant allele of the IL-6 promoter SNP -572 was associated with a roughly 2-fold increased risk of plasma cell neoplasms when cases were compared with family [odds ratio (OR), 1.8; 95% confidence interval (95% CI), 0.7-4.7] or population controls (OR, 2.4; 95% CI, 1.2-4.7). The -373 9A/9A genotype was associated with a decreased risk compared with the most common genotype (OR for cases versus family controls, 0.4; 95% CI, 0.1-1.7; OR for cases versus population controls, 0.3; 95% CI, 0.1-0.9). No other SNPs were associated with risk. Obesity (BMI >or= 30 kg/m(2)) increased risk nonsignificantly by 40% and 80% when cases were compared with family controls or population controls, respectively, relative to persons with a BMI of <25 kg/m(2). These results suggest that IL-6 promoter genotypes may be associated with increased risk of plasma cell neoplasms.

  3. Genotype distribution and the relative risk factors for human papillomavirus in Urumqi, China.

    Science.gov (United States)

    Chen, Zhifang; Meng, Wei; DU, Rong; Zhu, Yuejie; Zhang, Yi; Ding, Yan

    2013-07-01

    The aim of this study was to investigate human papillomavirus (HPV) infection and HPV genotype distributions in Urumqi, Xinjiang, China. The related risk factors for high-risk HPV infection was also analyzed. A stratified cluster sampling method was used for the population-based cervical cancer screening of women aged 18-69 years in the Urumqi Saybagh district. Exfoliated cervical cell samples were collected for liquid-based cytology detection and HPV genotyping DNA microarrays. Education level, number of sexual partners, condom use and occupation were used in the multivariate analysis model. The HPV infection rate of women working in service industries was significantly higher compared with those of white-collar workers, community residents and migrant workers. The 35-44-year-old migrant worker group had the highest HPV infection rates among all of the groups in the three different age ranges. The number of marriages, education level, smoking history, number of abortions, use of condoms, number of sexual partners, number of sexual partners in the past five years and occupation were all associated with female HPV infection rate (P<0.05). The 35-44-year-old women were the age group with the highest HPV infection rate. The HPV infection rate of females in service industries was the highest. Education level and condom use were protective factors of HPV infection, while the number of sexual partners and occupation were risk factors for HPV infection.

  4. Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk.

    Science.gov (United States)

    Li, Yulin; Ambrosone, Christine B; McCullough, Marjorie J; Ahn, Jiyoung; Stevens, Victoria L; Thun, Michael J; Hong, Chi-Chen

    2009-05-01

    Dietary antioxidants may interact with endogenous sources of pro- and antioxidants to impact breast cancer risk. A nested case-control study of postmenopausal women (505 cases and 502 controls) from the Cancer Prevention Study-II Nutrition Cohort was conducted to examine the interaction between oxidative stress-related genes and level of vegetable and fruit intake on breast cancer risk. Genetic variations in catalase (CAT) (C-262T), myeloperoxidase (MPO) (G-463A), endothelial nitric oxide synthase (NOS3) (G894T) and heme oxygenase-1 (HO-1) [(GT)(n) dinucleotide length polymorphism] were not associated with breast cancer risk. Women carrying the low-risk CAT CC [odds ratio (OR) = 0.75, 95% confidence interval (CI) 0.50-1.11], NOS3 TT (OR = 0.54, 95% CI = 0.26-1.12, P-trend = 0.10) or HO-1 S allele and MM genotype (OR = 0.56, 95% CI = 0.37-0.55), however, were found to be at non-significantly reduced breast cancer risk among those with high vegetable and fruit intake (> or = median; P-interactions = 0.04 for CAT, P = 0.005 for NOS3 and P = 0.07 for HO-1). Furthermore, those with > or = 4 putative low-risk alleles in total had significantly reduced risk (OR = 0.53, 95% CI = 0.32-0.88, P-interaction = 0.006) compared with those with fruit intake ( or = 4 low-risk alleles compared with participants with < or = 2 low-risk alleles (OR = 1.77, 95% CI = 1.05-2.99, P-interaction = 0.006). Our results support the hypothesis that there are joint effects of endogenous and exogenous antioxidants.

  5. Estimation of apolipoprotein E genotype-specific relative mortality risks from the distribution of genotypes in centenarians and middle-aged men

    DEFF Research Database (Denmark)

    Gerdes, Lars Ulrik; Jeune, B; Ranberg, K A

    2000-01-01

    We developed a method to estimate genotype-specific average relative mortality risk, R, from genotype distributions in cross-sectional studies of people belonging to different age-groups, and applied the method to new data from a study of apolipoprotein E genotypes (apoE) in 177 Danish centenarians...... and a Finnish study of centenarians, whereas the values for epsilon 2-carriers were about 0.90 with these data. The method to estimate mortality risk and the results associate with the view that the apoE gene is a "frailty gene." On the other hand, if odds ratios are used to summarize data from studies...... of this kind, they are more impressive and may propagate the misconception that apoE is a "longevity gene"....

  6. MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome

    DEFF Research Database (Denmark)

    Andersson, U.; Osterman, P.; Sjostrom, S.

    2009-01-01

    The human telomerase reverse transcriptase (hTERT) gene is upregulated in a majority of malignant tumours. A variable tandem repeat, MNS16A, has been reported to be of functional significance for hTERT expression. Published data on the clinical relevance of MNS16A variants in brain tumours have......-based genotyping all study subjects with fragments of 240 or 271 bp were judged as having short (S) alleles and subjects with 299 or 331 bp fragments as having long (L) alleles. Relative risk of glioma or meningioma was estimated with logistic regression adjusting for age, sex and country. Overall survival...

  7. Correlations between major risk factors and closely related Mycobacterium tuberculosis isolates grouped by three current genotyping procedures: a population-based study in northeast Mexico.

    Science.gov (United States)

    Peñuelas-Urquides, Katia; Martínez-Rodríguez, Herminia Guadalupe; Enciso-Moreno, José Antonio; Molina-Salinas, Gloria María; Silva-Ramírez, Beatriz; Padilla-Rivas, Gerardo Raymundo; Vera-Cabrera, Lucio; Torres-de-la-Cruz, Víctor Manuel; Martínez-Martínez, Yazmin Berenice; Ortega-García, Jorge Luis; Garza-Treviño, Elsa Nancy; Enciso-Moreno, Leonor; Saucedo-Cárdenas, Odila; Becerril-Montes, Pola; Said-Fernández, Salvador

    2014-09-01

    The characteristics of tuberculosis (TB) patients related to a chain of recent TB transmissions were investigated. Mycobacterium tuberculosis (MTB) isolates (120) were genotyped using the restriction fragment length polymorphism-IS6110 (R), spacer oligotyping (S) and mycobacterial interspersed repetitive units-variable number of tandem repeats (M) methods. The MTB isolates were clustered and the clusters were grouped according to the similarities of their genotypes. Spearman's rank correlation coefficients between the groups of MTB isolates with similar genotypes and those patient characteristics indicating a risk for a pulmonary TB (PTB) chain transmission were ana- lysed. The isolates showing similar genotypes were distributed as follows: SMR (5%), SM (12.5%), SR (1.67%), MR (0%), S (46.67%), M (5%) and R (0%). The remaining 35 cases were orphans. SMR exhibited a significant correlation (p < 0.05) with visits to clinics, municipalities and comorbidities (primarily diabetes mellitus). S correlated with drug consumption and M with comorbidities. SMR is needed to identify a social network in metropolitan areas for PTB transmission and S and M are able to detect risk factors as secondary components of a transmission chain of TB.

  8. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.

    Science.gov (United States)

    Liu, Jimmy Z; Hov, Johannes Roksund; Folseraas, Trine; Ellinghaus, Eva; Rushbrook, Simon M; Doncheva, Nadezhda T; Andreassen, Ole A; Weersma, Rinse K; Weismüller, Tobias J; Eksteen, Bertus; Invernizzi, Pietro; Hirschfield, Gideon M; Gotthardt, Daniel Nils; Pares, Albert; Ellinghaus, David; Shah, Tejas; Juran, Brian D; Milkiewicz, Piotr; Rust, Christian; Schramm, Christoph; Müller, Tobias; Srivastava, Brijesh; Dalekos, Georgios; Nöthen, Markus M; Herms, Stefan; Winkelmann, Juliane; Mitrovic, Mitja; Braun, Felix; Ponsioen, Cyriel Y; Croucher, Peter J P; Sterneck, Martina; Teufel, Andreas; Mason, Andrew L; Saarela, Janna; Leppa, Virpi; Dorfman, Ruslan; Alvaro, Domenico; Floreani, Annarosa; Onengut-Gumuscu, Suna; Rich, Stephen S; Thompson, Wesley K; Schork, Andrew J; Næss, Sigrid; Thomsen, Ingo; Mayr, Gabriele; König, Inke R; Hveem, Kristian; Cleynen, Isabelle; Gutierrez-Achury, Javier; Ricaño-Ponce, Isis; van Heel, David; Björnsson, Einar; Sandford, Richard N; Durie, Peter R; Melum, Espen; Vatn, Morten H; Silverberg, Mark S; Duerr, Richard H; Padyukov, Leonid; Brand, Stephan; Sans, Miquel; Annese, Vito; Achkar, Jean-Paul; Boberg, Kirsten Muri; Marschall, Hanns-Ulrich; Chazouillères, Olivier; Bowlus, Christopher L; Wijmenga, Cisca; Schrumpf, Erik; Vermeire, Severine; Albrecht, Mario; Rioux, John D; Alexander, Graeme; Bergquist, Annika; Cho, Judy; Schreiber, Stefan; Manns, Michael P; Färkkilä, Martti; Dale, Anders M; Chapman, Roger W; Lazaridis, Konstantinos N; Franke, Andre; Anderson, Carl A; Karlsen, Tom H

    2013-06-01

    Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.

  9. CYP2C9 genotypes modify benzodiazepine-related fall risk: Original results from three studies with meta-analysis

    NARCIS (Netherlands)

    Ham, A.C.; Ziere, Gijsbertus; Broer, Linda; Wijngaarden, van J.P.; Zwaluw, van der N.L.; Brouwer, E.M.; Dhonukshe-Rutten, R.A.M.; Groot, de C.P.G.M.; Witkamp, R.F.

    2017-01-01

    Objective.
    To investigate whether the CYP2C9*2 and *3 variants modify benzodiazepine-related fall risk.
    Design.
    Three prospective studies; the Rotterdam Study, B-PROOF, and LASA.
    Setting.
    Community-dwelling individuals living in or near five Dutch cities.
    Participants.
    Th

  10. CYP2C9 genotype does not affect risk of tobacco-related cancer in the general population

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Nordestgaard, B.G.; Bojesen, S.E.

    2010-01-01

    tolbutamide and warfarin, while this has not been investigated for PAHs. We hypothesised that these two variants in the CYP2C9 gene influence risk of tobacco-related cancer. Methods: In a prospective study of the general population (n = 10 392) with 60 years of follow-up, the Copenhagen City Heart Study, we.......9/1.1 in the Copenhagen City Heart Study and below/above 0.8/1.3 and 0.9/1.1 in the Copenhagen General Population Study for tobacco-related cancer and all cancer, respectively. Conclusion: Genetic variations in CYP2C9 do not affect risk of tobacco-related cancers. (C) 2010 Elsevier Ltd. All rights reserved...... associated two variants of CYP2C9 (CYP2C9*2 and CYP2C9*3) with risk of tobacco-related cancer and all cancer. All results were re-tested in a cross-sectional study of the general population (n = 36 856), the Copenhagen General Population Study. Results: We found no association between any of the CYP2C9...

  11. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis

    NARCIS (Netherlands)

    Liu, Jimmy Z.; Hov, Johannes Roksund; Folseraas, Trine; Ellinghaus, Eva; Rushbrook, Simon M.; Doncheva, Nadezhda T.; Andreassen, Ole A.; Weersma, Rinse K.; Weismueller, Tobias J.; Eksteen, Bertus; Invernizzi, Pietro; Hirschfield, Gideon M.; Gotthardt, Daniel Nils; Pares, Albert; Ellinghaus, David; Shah, Tejas; Juran, Brian D.; Milkiewicz, Piotr; Rust, Christian; Schramm, Christoph; Mueller, Tobias; Srivastava, Brijesh; Dalekos, Georgios; Noethen, Markus M.; Herms, Stefan; Winkelmann, Juliane; Mitrovic, Mitja; Braun, Felix; Ponsioen, Cyriel Y.; Croucher, Peter J. P.; Sterneck, Martina; Teufel, Andreas; Mason, Andrew L.; Saarela, Janna; Leppa, Virpi; Dorfman, Ruslan; Alvaro, Domenico; Floreani, Annarosa; Onengut-Gumuscu, Suna; Rich, Stephen S.; Thompson, Wesley K.; Schork, Andrew J.; Naess, Sigrid; Thomsen, Ingo; Mayr, Gabriele; Koenig, Inke R.; Hveem, Kristian; Cleynen, Isabelle; Gutierrez-Achury, Javier; Ricano-Ponce, Isis; van Heel, David; Bjoernsson, Einar; Sandford, Richard N.; Durie, Peter R.; Melum, Espen; Vatn, Morten H.; Silverberg, Mark S.; Duerr, Richard H.; Padyukov, Leonid; Brand, Stephan; Sans, Miquel; Annese, Vito; Achkar, Jean-Paul; Boberg, Kirsten Muri; Marschall, Hanns-Ulrich; Chazouilleres, Olivier; Bowlus, Christopher L.; Wijmenga, Cisca; Schrumpf, Erik; Vermeire, Severine; Albrecht, Mario; Rioux, John D.; Alexander, Graeme; Bergquist, Annika; Cho, Judy; Schreiber, Stefan; Manns, Michael P.; Farkkila, Martti; Dale, Anders M.; Chapman, Roger W.; Lazaridis, Konstantinos N.; Franke, Andre; Anderson, Carl A.; Karlsen, Tom H.

    Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation(1-3). We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped

  12. Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis.

    Directory of Open Access Journals (Sweden)

    Xue-bin Wang

    Full Text Available Homocysteine (Hcy is a potential risk factor for age-related cataract (ARC. Methylenetetrahydrofolate reductase (MTHFR is the key enzyme for Hcy metabolism, and variants of MTHFR may affect MTHFR enzyme activity. This study mainly evaluated the associations between variants in MTHFR gene, plasma MTHFR enzyme activity, total Hcy (tHcy levels and ARC risk in Chinese population. Four single nucleotide polymorphisms (SNPs in MTHFR gene were genotyped using the high-resolution melting (HRM method in 502 ARC patients (mean age, 70.2 [SD, 9.0], 46.0% male and 890 healthy controls (mean age, 67.1 [SD, 11.1], 47.6% male. The plasma MTHFR activity, folic acid (FA, vitamins B12 and B6 levels were detected by enzyme-linked immunosorbent assays (ELISA. The plasma tHcy levels were measured by an automated enzymatic assay. After the Bonferroni correction, the minor allele T of SNP rs1801133 showed a significant association with an increased risk of overall ARC (OR = 1.26, P = 0.003. Consistent association was also found between SNP rs1801133 and cortical ARC risk (OR = 1.44, P = 0.003. Haplotype analyses revealed an adverse effect of the haplotype "C-A-T-C" (alleles in order of SNPs rs3737967, rs1801131, rs1801133 and rs9651118 on ARC risk (OR = 1.55, P = 0.003. Moreover, in a joint analysis of SNPs rs9651118 and rs1801133, subjects with two unfavorable genotypes had a 1.76-fold increased risk of ARC compared with the reference group, and a statistically significant dose-response trend (Ptrend = 0.001 was also observed. Further, in healthy controls and patients with cortical ARC, the allele T of SNP rs1801133 and the increasing number of unfavorable genotypes were significantly correlated with decreased MTHFR activity as well as increased tHcy levels. However, there was no significant association between FA, vitamins B12, B6 levels and MTHFR variants. Our data indicated that variants in MTHFR gene might individually and jointly influence susceptibility to ARC

  13. The NEI/NCBI dbGAP database: Genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Miller Joan W

    2008-06-01

    Full Text Available Abstract Background To examine if the significantly associated SNPs derived from the genome wide allelic association study on the AREDS cohort at the NEI (dbGAP specifically confer risk for neovascular age-related macular degeneration (AMD. We ascertained 134 unrelated patients with AMD who had one sibling with an AREDS classification 1 or less and was past the age at which the affected sibling was diagnosed (268 subjects. Genotyping was performed by both direct sequencing and Sequenom iPLEX system technology. Single SNP analyses were conducted with McNemar's Test (both 2 × 2 and 3 × 3 tests and likelihood ratio tests (LRT. Conditional logistic regression was used to determine significant gene-gene interactions. LRT was used to determine the best fit for each genotypic model tested (additive, dominant or recessive. Results Before release of individual data, p-value information was obtained directly from the AREDS dbGAP website. Of the 35 variants with P -6 examined, 23 significantly modified risk of neovascular AMD. Many variants located in tandem on 1q32-q22 including those in CFH, CFHR4, CFHR2, CFHR5, F13B, ASPM and ZBTB were significantly associated with AMD risk. Of these variants, single SNP analysis revealed that CFH rs572515 was the most significantly associated with AMD risk (P -6. Haplotype analysis supported our findings of single SNP association, demonstrating that the most significant haplotype, GATAGTTCTC, spanning CFH, CFHR4, and CFHR2 was associated with the greatest risk of developing neovascular AMD (P -6. Other than variants on 1q32-q22, only two SNPs, rs9288410 (MAP2 on 2q34-q35 and rs2014307 (PLEKHA1/HTRA1 on 10q26 were significantly associated with AMD status (P = .03 and P -6 respectively. After controlling for smoking history, gender and age, the most significant gene-gene interaction appears to be between rs10801575 (CFH and rs2014307 (PLEKHA1/HTRA1 (P -11. The best genotypic fit for rs10801575 and rs2014307 was an

  14. Celiac disease and HLA-DQ genotype: diagnosis of different genetic risk profiles related to the age in Badajoz, southwestern Spain

    Directory of Open Access Journals (Sweden)

    María Jesús Fernández-Cavada-Pollo

    2013-09-01

    Full Text Available Background and objectives:celiac disease is associated with the HLA class II alleles: DQA1*05-DQB1*02 and DQB1*0302. The genetic risk for celiac disease may depend on the presence or absence of such alleles, their combination or number of copies. This study aimed to establish the differences in HLA genotypes between celiac patients diagnosed during childhood and adulthood, and between patients and healthy controls, and to determine the risk of disease in each genotypic category. Methods: we classified 350 celiac patients at time of diagnosis and 218 controls into 14 categories according to their HLA genotype, based on the presence or absence of risk alleles. Results: we found statistically significant differences between the genotype frequencies of celiac patients diagnosed as being children and adults. DQA1*05 (x 1 copy, DQB1*02 (x 1 copy, DQB1*0302 (x 0 copies was the most frequent genotype in individuals diagnosed in childhood, whereas DQA1*05 (x 1 copy, DQB1*02 (x 2 copies, DQB1*0302 (x 0 copies was the most frequent in adults. The risk for disease in each genotypic category in celiac children and adults turned out to be different. The presence of DQB1*0302 did not increase risk in children, but did in adults. Conclusion: in our celiac population, we found a different genetic pattern according to age of diagnosis. That could suggest that the pathogenic mechanism of the disease is not exactly the same in both age groups, which could somehow determine clinical presentation of the disease, its epidemiology, coexisting diseases, and complications.

  15. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci.

    Science.gov (United States)

    Cortes, Adrian; Hadler, Johanna; Pointon, Jenny P; Robinson, Philip C; Karaderi, Tugce; Leo, Paul; Cremin, Katie; Pryce, Karena; Harris, Jessica; Lee, Seunghun; Joo, Kyung Bin; Shim, Seung-Cheol; Weisman, Michael; Ward, Michael; Zhou, Xiaodong; Garchon, Henri-Jean; Chiocchia, Gilles; Nossent, Johannes; Lie, Benedicte A; Førre, Øystein; Tuomilehto, Jaakko; Laiho, Kari; Jiang, Lei; Liu, Yu; Wu, Xin; Bradbury, Linda A; Elewaut, Dirk; Burgos-Vargas, Ruben; Stebbings, Simon; Appleton, Louise; Farrah, Claire; Lau, Jonathan; Kenna, Tony J; Haroon, Nigil; Ferreira, Manuel A; Yang, Jian; Mulero, Juan; Fernandez-Sueiro, Jose Luis; Gonzalez-Gay, Miguel A; Lopez-Larrea, Carlos; Deloukas, Panos; Donnelly, Peter; Bowness, Paul; Gafney, Karl; Gaston, Hill; Gladman, Dafna D; Rahman, Proton; Maksymowych, Walter P; Xu, Huji; Crusius, J Bart A; van der Horst-Bruinsma, Irene E; Chou, Chung-Tei; Valle-Oñate, Raphael; Romero-Sánchez, Consuelo; Hansen, Inger Myrnes; Pimentel-Santos, Fernando M; Inman, Robert D; Videm, Vibeke; Martin, Javier; Breban, Maxime; Reveille, John D; Evans, David M; Kim, Tae-Hwan; Wordsworth, Bryan Paul; Brown, Matthew A

    2013-07-01

    Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

  16. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

    Science.gov (United States)

    Cortes, Adrian; Hadler, Johanna; Pointon, Jenny P; Robinson, Philip C; Karaderi, Tugce; Leo, Paul; Cremin, Katie; Pryce, Karena; Harris, Jessica; lee, Seunghun; Joo, Kyung Bin; Shim, Seung-Cheol; Weisman, Michael; Ward, Michael; Zhou, Xiaodong; Garchon, Henri-Jean; Chiocchia, Gilles; Nossent, Johannes; Lie, Benedicte A; Førre, Øystein; Tuomilehto, Jaakko; Laiho, Kari; Jiang, Lei; Liu, Yu; Wu, Xin; Bradbury, Linda A; Elewaut, Dirk; Burgos-Vargas, Ruben; Stebbings, Simon; Appleton, Louise; Farrah, Claire; Lau, Jonathan; Kenna, Tony J; Haroon, Nigil; Ferreira, Manuel A; Yang, Jian; Mulero, Juan; Fernandez-Sueiro, Jose Luis; Gonzalez-Gay, Miguel A; lopez-Larrea, Carlos; Deloukas, Panos; Donnelly, Peter; Bowness, Paul; Gafney, Karl; Gaston, Hill; Gladman, Dafna D; Rahman, Proton; Maksymowych, Walter P; Xu, Huji; Crusius, J Bart A; van der Horst-Bruinsma, Irene E; Chou, Chung-Tei; Valle-Oñate, Raphael; Romero-Sánchez, Consuelo; Hansen, Inger Myrnes; Pimentel-Santos, Fernando M; Inman, Robert D; Videm, Vibeke; Martin, Javier; Breban, Maxime; Reveille, John D; Evans, David M; Kim, Tae-Hwan; Wordsworth, Bryan Paul; Brown, Matthew A

    2013-01-01

    Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis–associated haplotypes at 11 loci. Two ankylosing spondylitis–associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression. PMID:23749187

  17. Myeloperoxidase genotype, fruit and vegetable consumption, and breast cancer risk.

    Science.gov (United States)

    Ahn, Jiyoung; Gammon, Marilie D; Santella, Regina M; Gaudet, Mia M; Britton, Julie A; Teitelbaum, Susan L; Terry, Mary Beth; Neugut, Alfred I; Josephy, P David; Ambrosone, Christine B

    2004-10-15

    Myeloperoxidase (MPO), an antimicrobial enzyme in the breast, generates reactive oxygen species (ROS) endogenously. An MPO G463A polymorphism exists in the promoter region, with the variant A allele conferring lower transcription activity than the common G allele. Because oxidative stress may play a role in breast carcinogenesis, we evaluated MPO genotypes in relation to breast cancer risk among 1,011 cases and 1,067 controls from the Long Island Breast Cancer Study Project (1996-1997). We also assessed the potential modifying effects of dietary antioxidants and hormonally related risk factors on these relationships. Women over 20 years with incident breast cancer who were residents of Nassau and Suffolk Counties, NY, were identified as potential cases. Population-based controls were frequency matched by 5-year age groups. Genotyping was performed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) technology, and suspected breast cancer risk factors and usual dietary intake were assessed during an in-person interview. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals. Having at least one A allele was associated with an overall 13% reduction in breast cancer risk. When consumption of fruits and vegetables and specific dietary antioxidants were dichotomized at the median, inverse associations with either GA or AA genotypes were most pronounced among women who consumed higher amounts of total fruits and vegetables (odds ratio, 0.75; 95% confidence interval, 0.58-0.97); this association was not noted among the low-consumption group (P for interaction = 0.04). Relationships were strongest among premenopausal women. Results from this first study of MPO genotypes and breast cancer risk indicate that MPO variants, related to reduced generation of ROS, are associated with decreased breast cancer risk, and emphasize the importance of fruit and vegetable consumption in reduction of breast

  18. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke

    DEFF Research Database (Denmark)

    Khan, Tauseef A; Shah, Tina; Prieto, David;

    2013-01-01

    At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less...

  19. Changes in lifestyle, biological risk factors and total homocysteine in relation to MTHFR C677T genotype: a 5-year follow-up study

    DEFF Research Database (Denmark)

    Linneberg, A; Thuesen, Betina Heinsbæk; Jørgensen, Torben

    2009-01-01

    BACKGROUND/OBJECTIVES: Total homocysteine (tHcy) has been associated with increased risk of several diseases in the general population. It is not clear whether these associations are causal. A less healthy lifestyle as well as a less favorable biological risk factor profile have been related...... to increased tHcy in cross-sectional studies. In addition, the methylenetetrahydrofolate reductase (MTHFR) C677T gene variant is an important determinant of elevated tHcy. The main objective of the study was to examine the effect of changes in biological risk factors and lifestyle on tHcy in relation to MTHFR......, physical activity, smoking status, coffee, tea, total alcohol or wine consumption. An inverse relationship was observed between changes in tHcy and changes in the intake of beer in TT individuals but not in CC/CT individuals (P (interaction)=0.01). In addition, changes in tHcy were positively associated...

  20. Hepatitis C virus genotypes distribution and transmission risk factors in Luxembourg from 1991 to 2006

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To analyze the Hepatitis C virus (HCV) genotype distribution and transmission risk factors in a population of unselected patients in Luxembourg. METHODS: Epidemiological information (gender, age and transmission risks) were collected from 802patients newly diagnosed for hepatitis C and living in Luxembourg, among whom 228 patients referred from prison. Genotyping using 5'noncoding (5'NC) sequencing was performed. We compared categorical data using the Fisher's exact F-test and odds ratios (OR) were calculated for evaluating association of HCV genotype and risk factors. RESULTS: The sex ratio was predominantly male (2.2) and individuals aged less than 40 years represented 49.6% of the population. Genotype l was predominant (53.4%) followed by genotype 3 (33%). Among risk factors, intravenous drug usage (IVDU) was the most frequently reported (71.4%) followed by medical-related transmission (17.6%) including haernophilia, transfusion recipients and other nosocomial reasons. Genotype 3was significantly associated to IVDU (OR=4.84,P<0.0001= whereas genotype l was significantly associated with a medical procedure (OR = 2.42,P<0.001=.The HCV genotype distribution from inmate patients differed significantly from the rest of the population (Chi-square test with four degrees of freedom, P<0.0001= with a higher frequency of genotype 3 (46.5% vs 27.5%) and a lower frequency of genotype 1 and 4 (44.7% vs 56.8%and 5.3% vs 9.6%,respectively).IVDU was nearly exclusively reported as a risk factor in prison. CONCLUSION: We report the first description of the HCV genotype distribution in Luxembourg. The repartition is similar to other European countries, with one of the highest European prevalence rates of genotype 3 (33%). Since serology screening became available in 1991,IVDU remains the most common way of HCV transmission in Luxembourg.

  1. Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women.

    Science.gov (United States)

    Bräuner, Elvira V; Loft, Steffen; Wellejus, Anja; Autrup, Herman; Tjønneland, Anne; Raaschou-Nielsen, Ole

    2014-01-01

    Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in estrogen metabolism and PCB metabolism, both of which may relate to breast cancer susceptibility. Polymorphisms in genes regulating these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk. When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We found no statistically significant interactions between any of the PCB groups and CYP1B1 or COMT polymorphisms on the risk of breast cancer.

  2. Assessment of the association between GSTM1 null genotype and risk of type 2 diabetes.

    Science.gov (United States)

    Yi, Ran; Liu, Bin; Dong, Qi

    2013-06-01

    Many studies have investigated the association between Glutathione S-Transferase M1 (GSTM1) null genotype and risk of diabetes mellitus, but the impact of GSTM1 null genotype on diabetes mellitus is unclear owing to the obvious inconsistence among those studies. This study aimed to quantify the strength of association between GSTM1 null genotype and risk of diabetes mellitus. We searched the PubMed, Embase and Wangfang databases for studies relating the association between GSTM1 null genotype and risk of diabetes mellitus. We estimated summary odds ratio (OR) with their 95 % confidence interval (95 % CI) to assess the association. Subgroup analyses were performed by type of diabetes and ethnicity. 10 case-control studies with 7, 054 subjects were included into this meta-analysis. Meta-analysis of total 10 studies showed GSTM1 null genotype was associated increased risk of diabetes mellitus (OR = 1.59, 95 % CI 1.14-2.22, P = 0.007). Subgroup analyses by type of diabetes mellitus suggested GSTM1 null genotype was associated increased risk of type 2 diabetes (OR = 1.90, 95 % CI 1.37-2.64, P null genotype and increased risk of type 2 diabetes. The cumulative meta-analyses showed a trend of obvious association between GSTM1 null genotype and risk of type 2 diabetes as information accumulated. No evidence of publication bias was observed. Thus, evidence from current meta-analysis suggests an association between GSTM1 null genotype and risk of type 2 diabetes.

  3. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...... and have decreasing relative risk premium. We finally introduce the notion of partial risk neutral preferences on binary lotteries and show that partial risk neutrality is equivalent to preferences with decreasing relative risk premium...

  4. Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women

    DEFF Research Database (Denmark)

    Bräuner, Elvira; Loft, Steffen; Wellejus, Anja

    2014-01-01

    these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk....... When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We...

  5. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...... premium as the quotient between the risk premium and the increase in wealth y1–x which the decision maker puts on the line by choosing the lottery in place of receiving y1 with certainty. We study preferences such that the relative risk premium is a decreasing function of present wealth, and we determine...... relative risk premium in the small implies decreasing relative risk premium in the large, and decreasing relative risk premium everywhere implies risk aversion. We finally show that preferences with decreasing relative risk premium may be equivalently expressed in terms of certain preferences on risky...

  6. The Analysis of HPV Genotypes and Related High Risk Factors in 459 Women of Annual Health Examination%459例女性健康体检者HPV基因型及高危因素分析

    Institute of Scientific and Technical Information of China (English)

    陈秀杰; 李艳玲; 曲芃芃

    2014-01-01

    目的:研究459例女性健康体检者宫颈人乳头瘤病毒(HPV)感染情况、基因型别分布及其高危因素。方法采用巢式PCR和焦磷酸测序技术检测459例受检者宫颈脱落细胞中HPV分型情况,同时收集受检者一般资料、月经婚育史、生殖道疾病既往史,分析HPV感染的相关危险因素。结果 HPV阳性检出率为17.9%,共检测出7种高危基因型别,其中HPV16检出率最高(9.8%),其次是HPV58(7.0%),HPV18(5.2%)。单纯感染、双重感染、多重感染的检出率分别是9.6%、4.8%、1.5%。饮酒、经济收入<3000元/月、性伴侣>1个、性生活频率>4次/月、伴有宫颈糜烂是HPV感染的危险因素(P<0.05)。结论 HPV DNA基因型别检测可为宫颈癌的早期筛查和HPV疫苗的研发使用提供重要信息,为高危人群的早预防、早诊断、早治疗提供重要依据。%Objective To investigate the cervical human papillomavirus (HPV) infection, genotypes and related high risk factors in 459 women of annual health examination. Methods A total of 459 cervical cytology specimens were de-tected with nest PCR and pyrosequencing methods. Questionnaires were collected simultaneously and the risk factors of HPV infection were analyzed. Results The detection rate of HPV-positive samples was 17.9%. Seven kinds of high-risk genotypes of HPV were found. The detection of HPV 16 was the most common (9.8%), followed by HPV58 (7.0%) and HPV18 (5.2%). The detection rates of simplex infection, dual infections and multiple infections were 9.6%, 4.8%and 1.5%respectively. The risk factors for HPV infection included alcohol consumption,income 1, frequency of sexual activity>4 times/month and cervical erosion (P<0.05). Conclusion HPV DNA genotyping can provide important reference for HPV screening at early time and the application of HPV vaccines, which also provide sig-nificant evidence for the prevention, diagnosis and treatment of cervical

  7. Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women

    DEFF Research Database (Denmark)

    Bräuner, Elvira V; Loft, Steffen; Wellejus, Anja;

    2014-01-01

    Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in estrogen metabolism and PCB metabolism, both of which may relate to breast cancer susceptibility. Polymorphisms in genes regulating...

  8. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    We consider the risk premium demanded by a decision maker in order to be indifferent between obtaining a new level of wealth with certainty, or to participate in a lottery which either results in unchanged wealth or an even higher level than what can be obtained with certainty. We study preferences...... such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...... and have decreasing relative risk premium. We finally introduce the notion of partial risk neutral preferences on binary lotteries and show that partial risk neutrality is equivalent to preferences with decreasing relative risk premium...

  9. Alcohol dehydrogenase 3 genotype as a risk factor for upper aerodigestive tract cancers

    DEFF Research Database (Denmark)

    Nishimoto, Inês Nobuko; Pinheiro, Nidia A; Rogatto, Silvia R

    2004-01-01

    for ADH3 genotypes using logistic regression models. RESULTS: After adjustment for sex, age, tobacco use, and history of cancer in first-degree family relatives, a significantly higher odds ratio for UADT cancer was observed among individuals with AA genotype and low cumulative alcohol consumption...... (tobacco consumption (... be a risk factor for UADT cancer, especially in individuals with low alcohol or tobacco consumption. However, further epidemiological case-control or cohort studies, preferably prospective, are needed to establish the exact role of ADH3 polymorphism and its association with the development of UADT cancers....

  10. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...

  11. HCV genotype distribution and possible transmission risks in Lahore, Pakistan

    Institute of Scientific and Technical Information of China (English)

    Waqar; Ahmad; Bushra; Ijaz; Fouzia; Tahir; Javed; Shah; Jahan; Imran; Shahid; Fawad; Mumtaz; Khan; Sajida; Hassan

    2010-01-01

    AIM: To investigate the prevalence of hepatitis C virus (HCV) genotypes and their association with possible transmission routes in the general population of Lahore, as the data exclusively related to this city is limited. METHODS: Complete data regarding patient's history, possible route of infection and biochemical tests was collected from the public hospital for 1364 patients. SPSS version 16 windows software was used for data analysis by univariate and multivariate techniques. RESULTS: Age range ≤ 40 yea...

  12. Fuel related risks; Braenslerisker

    Energy Technology Data Exchange (ETDEWEB)

    Englund, Jessica; Sernhed, Kerstin; Nystroem, Olle; Graveus, Frank (Grontmij AB, (Sweden))

    2012-02-15

    The project, within which this work report was prepared, aimed to complement the Vaermeforsk publication 'Handbook of fuels' on fuel related risks and measures to reduce the risks. The fuels examined in this project where the fuels included in the first version of the handbook from 2005 plus four additional fuels that will be included in the second and next edition of the handbook. Following fuels were included: woodfuels (sawdust, wood chips, powder, briquettes), slash, recycled wood, salix, bark, hardwood, stumps, straw, reed canary grass, hemp, cereal, cereal waste, olive waste, cocoa beans, citrus waste, shea, sludge, forest industrial sludge, manure, Paper Wood Plastic, tyre, leather waste, cardboard rejects, meat and bone meal, liquid animal and vegetable wastes, tall oil pitch, peat, residues from food industry, biomal (including slaughterhouse waste) and lignin. The report includes two main chapters; a general risk chapter and a chapter of fuel specific risks. The first one deals with the general concept of risk, it highlights laws and rules relevant for risk management and it discuss general risks that are related to the different steps of fuel handling, i.e. unloading, storing, processing the fuel, transportation within the facility, combustion and handling of ashes. The information that was used to produce this chapter was gathered through a literature review, site visits, and the project group's experience from risk management. The other main chapter deals with fuel-specific risks and the measures to reduce the risks for the steps of unloading, storing, processing the fuel, internal transportation, combustion and handling of the ashes. Risks and measures were considered for all the biofuels included in the second version in the handbook of fuels. Information about the risks and risk management was gathered through interviews with people working with different kinds of fuels in electricity and heat plants in Sweden. The information from

  13. Glutathione S-transferase M1 null genotype related to poor prognosis of colorectal cancer.

    Science.gov (United States)

    Yan, Shushan; Wang, Zengfang; Wang, Zengyan; Duan, Quanhong; Wang, Xiaochen; Li, Jun; Sun, Beicheng

    2016-08-01

    Published studies showed controversial findings about the relationship between glutathione S-transferase M1 (GSTM1) null genotype and clinical outcomes of patients with colorectal cancer. We performed a meta-analysis to quantitatively assess the association between GSTM1 null genotype and prognosis of patients with colorectal cancer. We systematically searched Pubmed, Embase, and Web of Science to identify prospective or retrospective cohort studies assessing the association of GSTM1 null genotype with overall survival (OS) or disease-free survival (DFS) in colorectal cancer. The hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were used to assess the association of GSTM1 null genotype with OS or DFS. Finally, 15 studies from 14 publications with 4326 colorectal cancer patients were included into the meta-analysis. There was no heterogeneity in the meta-analysis relating OS (I (2) = 0 %) and DFS (I (2) = 0 %). Overall, GSTM1 null genotype was significantly associated with poor OS in patients with colorectal cancer (HR = 1.18, 95 % CI 1.07-1.30, P = 0.001). In addition, GSTM1 null genotype was also significantly associated with poor DFS in patients with colorectal cancer (HR = 1.15, 95 % CI 1.03-1.28, P = 0.015). No obvious risk of publication bias was observed. GSTM1 null genotype is significantly associated with poor OS and DFS in patients with colorectal cancer, which suggests that GSTM1 null genotype confers poor effect on the prognosis of colorectal cancer.

  14. The frequency of GSTT1 null genotype in Turkish population and lung cancer risk

    Directory of Open Access Journals (Sweden)

    Demir A

    2005-01-01

    Full Text Available BACKGROUND : Previous studies have suggested that Glutathione S -transferase (GST genotypes may play a role in determining susceptibility to lung cancer, though the data are often conflicting. In different ethnic groups variations in null allele frequency has been observed. AIMS: We aimed to evaluate whether genetic polymorphisms of Glutathione S -transferase theta (GSTT1 influence individual susceptibility to lung cancer in Turkish population. We tried to clarify the frequencies of GSTM1 gene polymorphisms in a Turkish population. METHODS: DNA samples, extracted from the whole blood were amplified using polymerase chain reaction (PCR method in all of the 68 cases, composed of 31 previously diagnosed lung cancer and 37 healthy controls. RESULTS: The prevalence of GSTT1 null genotype in the lung cancer patients was 29%, compared to 11% in control group. GSTT1 null genotype was found to be higher in cancer group compared to the control group, although it was not statistically significant (OR = 3.37, 95% CI = 0.92-12.32, P = 0.06. There was also no significant relation in GSTT1 genotypes among histopathology types of lung cancers. The frequency of GSTT1 was found to be 25.4% ( n = 952 when the studies of Turkish population were reviewed. CONCLUSION: It can be concluded that carrying the GSTT1 null genotype may be accepted as a weak risk factor for the susceptibility to lung cancer.

  15. Body mass index and obesity- and diabetes-associated genotypes and risk for pancreatic cancer.

    Science.gov (United States)

    Tang, Hongwei; Dong, Xiaoqun; Hassan, Manal; Abbruzzese, James L; Li, Donghui

    2011-05-01

    The genetic factors predisposing individuals with obesity or diabetes to pancreatic cancer have not been identified. To investigate the hypothesis that obesity- and diabetes-related genes modify the risk of pancreatic cancer. We genotyped 15 single nucleotide polymorphisms of fat mass and obesity-associated (FTO), peroxisome proliferators-activated receptor gamma (PPARγ), nuclear receptor family 5 member 2 (NR5A2), AMPK, and ADIPOQ genes in 1,070 patients with pancreatic cancer and 1,175 cancer-free controls. Information on risk factors was collected by personal interview. Adjusted ORs (AOR) and 95% CIs were calculated using unconditional logistic regression. The PPARγ P12A GG genotype was inversely associated with risk of pancreatic cancer (AOR, 0.21; 95% CI, 0.07-0.62). Three NR5A2 variants that were previously identified in a genome-wide association study were significantly associated with reduced risk of pancreatic cancer, AORs ranging from 0.57 to 0.79. Two FTO gene variants and one ADIPOQ variant were differentially associated with pancreatic cancer according to levels of body mass index (BMI; P(interaction) = 0.0001, 0.0015, and 0.03). For example, the AOR (95% CI) for FTO IVS1-2777AC/AA genotype was 0.72 (0.55-0.96) and 1.54 (1.14-2.09) in participants with a BMI of less than 25 or 25 kg/m(2) or more, respectively. We observed no significant association between AMPK genotype and pancreatic cancer and no genotype interactions with diabetes or smoking. Our findings suggest the PPARγ P12A GG genotype and NR5A2 variants may reduce the risk for pancreatic cancer. A positive association of FTO and ADIPOQ gene variants with pancreatic cancer may be limited to persons who are overweight. The discovery of genetic factors modifying the risk of pancreatic cancer may help to identify high-risk individuals for prevention efforts. ©2011 AACR.

  16. Risk Factors and Genotypes of Hepatitis C Virus Infection in Libyan Patients

    Directory of Open Access Journals (Sweden)

    Alashek WA

    2008-01-01

    Full Text Available Background: The prevalence and incidence of HCV infection varies geographically due to exposureto different risk factors. Identification of HCV genotype is important to defining the epidemiology of thedisease. The objective of this study was to describe genotype distribution and its relation to riskfactors among HCV infected patients attending virology clinic of the Department of InfectiousDiseases at the Tripoli Medical Centre. Methods: The medical records of 891 Libyan chronic HCVinfected patients registered and followed up from January 2003 to January 2007 were reviewed. Datagathered includes patient's age, gender, risk factors and family history of HCV infection. Statisticalanalysis was performed using t, x2 and contingency coefficient tests. Results: The mean age was40.22±13.09 years. Two thirds of patients were males. Normal alanine aminotransferase (ALT atdiagnosis was found in 62% of the patients. HCV RNA < 2 million copies at diagnosis was foundamong 54% of patients. HCV genotype 1 (G1 was the most frequent (30.9%, followed by G4(29.2%. Genotype 2 affected 19.3% and G3 13.6%. No classification of HCV genotype was availablefor 2% of the patients. Many subtypes of HCV were detected with different frequencies (G1a and b,G2a, b, c and a/c, G3a and G4a and c/d. All genotypes of HCV were more common among males(P<0.001. Genotype 3 was the most frequent among male patients (88.6%. Regarding the riskfactors, 33% of patients had a history of hospitalization and/or surgical procedures, and 22.7% had ahistory of blood transfusion. A past history of intravenous drug abuse (IVDA was reported by 15% ofthe patients, and 15.9% reported a history of dental procedures. The relationship between thegenotype of HCV and risk factors was statistically significant (P<0.001. No history of risky exposurewas found among 10.8% of patients. Conclusion: Genotypes 1 and 4 were more predominantamong HCV infected patients. Males were affected more than females and

  17. War exposure, 5-HTTLPR genotype and lifetime risk of depression.

    Science.gov (United States)

    Artero, Sylvaine; Touchon, Jacques; Dupuy, Anne-Marie; Malafosse, Alain; Ritchie, Karen

    2011-07-01

    In 1962 approximately 1.5 million French people living in Algeria were repatriated to France in very poor and often life-threatening conditions. These people constitute a cohort for the study of the long-term impact of gene-environment interaction on depression. To examine the interaction between a highly stressful life event and subsequent depression, and its modulation by a length polymorphism of the serotonin transporter gene (5-HTTLPR). A community sample of people aged 65 years and over residing in the Montpellier region of the south of France was randomly recruited from electoral rolls. Genotyping was performed on 248 repatriated persons and 632 controls. Current and lifetime major and minor depressive disorders were assessed according to DSM-IV criteria. A significant relationship was observed between exposure to repatriation and subsequent depression (Peducation, disability, recent life events and cognitive function, the gene-environment interaction (repatriation × 5-HTTLPR) was globally significant (P<0.002; OR = 3.21, 95% CI 2.48-5.12). Individuals carrying the two short (s) alleles of 5-HTTLPR were observed to be at higher risk (P<0.005; OR = 2.34, 95% CI 1.24-4.32), particularly when repatriation occurred before age 35 years (P<0.002; OR = 2.91, 95% CI 1.44-5.88), but this did not reach significance in those who were older at the time of the event (P = 0.067). The association between depression and war repatriation was significantly modulated by 5-HTTLPR genotype but this appeared to occur only in people who were younger at the time of exposure.

  18. Application of Microarray-Based Method for Functional SNP Genotyping in the Risk of Gastric Carcinoma in Chinese Population

    Institute of Scientific and Technical Information of China (English)

    Song Li; Meiju Ji; Peng Hou; Nongyue He; Hong Chen

    2006-01-01

    High-throughput SNP detection microarrays were used here to explore the relationship between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T and the risk of gastric carcinoma among population in Jiangsu region, by genotyping the specimens from 170 patients with gastric carcinoma and 140 age- and sexmatched control subjects. PCR products were spotted onto a 3-aminopropyltriethoxysilane coated glass slide to fabricate a microarray, then interrogated by hybridization with dual-color probes (Cy3, Cy5) to determine the SNP genotype of each sample, and the relation between the genotypes and the risk of gastric carcinoma was analyzed. The frequencies of C677T genotype were CC(47.9%), CT(40%), CT(12.1%) in control group and CC(35.9%), CT(45.9%), TT(18.2%) in gastric carcinoma group, respectively. The individuals with 677CT+TT genotype group or 677TT had a 1.67-fold (95% CI: 1.06-2.64)or 2.67-fold (95% CI: 1.382-5.341) increased risk to develop gastric carcinoma compared with those having 677CC genotype.It was shown that the single nucleotide polymorphisms in the MTHFR gene are associated with the risk of gastric carcinoma in the Chinese population.

  19. Cigarette smoking, N-acetyltransferase 2 genotypes, and breast cancer risk: pooled analysis and meta-analysis.

    Science.gov (United States)

    Ambrosone, Christine B; Kropp, Silke; Yang, Jun; Yao, Song; Shields, Peter G; Chang-Claude, Jenny

    2008-01-01

    Approximately 10 years ago, it was noted that smoking increased risk of breast cancer among women with N-acetyltransferase 2 (NAT2) slow acetylation genotypes. This report was followed by a number of studies to address this question. We pooled data from 10 existing studies and also conducted a meta-analysis of 13 studies published from 1996 to October 2006 that were conducted among women, were published in English, and had adequate information on smoking and NAT2 genotyping. Raw data were requested from authors. Unconditional logistic regression was done for pooled analysis, and random effect models was done for meta-analysis. Study heterogeneity was assessed, and sensitivity tests were done when subgroups were excluded from the analysis. In the pooled analysis, there was a significant interaction between smoking, NAT2 genotype, and risk of breast cancer [pack-years (continuous variable, P(interaction) = 0.03)], with higher pack-years significantly associated with an increased risk of breast cancer among women with NAT2 slow genotypes (pooled analysis relative risk, 1.49; 95% confidence interval, 1.08-2.04). These findings were supported by the meta-analysis including all studies; pack-years were significantly associated with risk among slow acetylators in a dose-dependent fashion (meta-analysis relative risk, 1.44; 95% confidence interval, 1.23-1.68 for > or =20 pack-years versus never smokers), but not among rapid acetylators. Similar relationships were noted for smoking status (ever, never) and duration of smoking. Our results show that cigarette smoking is associated with an increase in breast cancer risk among women with NAT2 slow acetylation genotypes. Because slow NAT2 genotypes are present in 50% to 60% of Caucasian populations, smoking is likely to play an important role in breast cancer etiology.

  20. Relation between hepatitis B virus genotypes and gene mutation of basic core promoter in Li nationality

    Institute of Scientific and Technical Information of China (English)

    Juntao Zeng; Zhengwen Liu; Shiping Zeng; Jing Chen

    2009-01-01

    Objective:To investigate the relation between hepatitis B virus(HBV) genotypes and the double mutation of A-to-T nucleotide(nt) 1762 and G-to-A nt 1764 in basic core promotev(BCP T1762/A1764) in patients of the Li nationality. Methods:Subjects were 125 HBV DNA positive patients that belong to the Li nationality on Hainan Island. HBV DNA genotype was determined by real time fluorimetrypolymerase chain reaction. BCP T1762/A1764 mutation was performed using the direct sequencing method. Results:The prevalence rates of genotype B, genotype C, genotype D, genotype C and D mixed infection(genotype C+D) and genotype B and D mixed infection (genotype B+C) were 31.20%, 53.60%, 12.00%, 2.40% and 0.80% respectively. Mutation frequencies in patients infected with HBV genotype C(58.21%) were significantly higher than in those infected with other genotypes (P <0.01). The serum viral load of the patients with genotype C(5.74±1.21) was also higher than that of those with genotype B(P <0.01). Conclusion:The major genotypes in the Li nationality were genotype C and genotype B. The infection of genotype D and mixed infection also occurred in the Li nationality. Genotype C HBV has a higher replication rate, and the different degrees of pathogenecity among HBV genotypes may be related to BCP T1762/ A1764 mutation frequency.

  1. Threat-related amygdala functional connectivity is associated with 5-HTTLPR genotype and neuroticism

    DEFF Research Database (Denmark)

    Madsen, Martin Korsbak; Mc Mahon, Brenda; Andersen, Sofie Bech

    2016-01-01

    and medial prefrontal cortex (mPFC) and between both amygdalae and a cluster including posterior cingulate cortex, precuneus and visual cortex was significantly increased in 5-HTTLPR S' allele carriers relative to L(A)L(A) individuals. Neuroticism was negatively correlated with functional connectivity......OFC/vlPFC, such that S' carriers exhibited a more negative association relative to L(A)L(A) individuals. These findings provide novel evidence for both independent and interactive effects of 5-HTTLPR genotype and neuroticism on amygdala communication, which may mediate effects on risk for mood and affective disorders....

  2. hTERT cancer risk genotypes are associated with telomere length.

    Science.gov (United States)

    Melin, Beatrice S; Nordfjäll, Katarina; Andersson, Ulrika; Roos, Göran

    2012-05-01

    Telomere biology is associated with cancer initiation and prognosis. Collected data suggest that blood cell telomere length (TL) can change over time, which may be related to development of common disorders, such as cardiovascular diseases and cancer. Recently, single nucleotide polymorphisms in the region of the human telomerase reverse transcriptase (hTERT) gene were associated with various malignancies, including glioma, lung and urinary bladder cancer, and telomerase RNA gene hTERC genotypes were recently linked to TL. In the present study a hypothetical association between identified genotypes in hTERT and hTERC genes and TL were investigated. We analyzed 21 polymorphisms, covering 90% of the genetic variance, in the hTERT gene, two genetic variants in hTERC, and relative TL(RTL) at average age 50 and 60 in 959 individuals with repeated blood samples. Mean RTL at age 60 was associated with four genetic variants of the hTERT gene (rs2736100, rs2853672, rs2853677, and rs2853676), two of which reported to be associated with cancer risk. Two alleles (rs12696304, rs16847897) near the hTERC gene were confirmed as also being associated with RTL at age 60. Our data suggest that hTERT and hTERC genotypes have an impact on TL of potential relevance and detectable first at higher ages, which gives us further insight to the complex regulation of TL.

  3. Threat-related amygdala functional connectivity is associated with 5-HTTLPR genotype and neuroticism.

    Science.gov (United States)

    Madsen, Martin Korsbak; Mc Mahon, Brenda; Andersen, Sofie Bech; Siebner, Hartwig Roman; Knudsen, Gitte Moos; Fisher, Patrick MacDonald

    2016-01-01

    Communication between the amygdala and other brain regions critically regulates sensitivity to threat, which has been associated with risk for mood and affective disorders. The extent to which these neural pathways are genetically determined or correlate with risk-related personality measures is not fully understood. Using functional magnetic resonance imaging, we evaluated independent and interactive effects of the 5-HTTLPR genotype and neuroticism on amygdala functional connectivity during an emotional faces paradigm in 76 healthy individuals. Functional connectivity between left amygdala and medial prefrontal cortex (mPFC) and between both amygdalae and a cluster including posterior cingulate cortex, precuneus and visual cortex was significantly increased in 5-HTTLPR S' allele carriers relative to L(A)L(A) individuals. Neuroticism was negatively correlated with functional connectivity between right amygdala and mPFC and visual cortex, and between both amygdalae and left lateral orbitofrontal (lOFC) and ventrolateral prefrontal cortex (vlPFC). Notably, 5-HTTLPR moderated the association between neuroticism and functional connectivity between both amygdalae and left lOFC/vlPFC, such that S' carriers exhibited a more negative association relative to L(A)L(A) individuals. These findings provide novel evidence for both independent and interactive effects of 5-HTTLPR genotype and neuroticism on amygdala communication, which may mediate effects on risk for mood and affective disorders.

  4. Estrogen receptor-alpha genotype affects exercise-related reduction of arterial stiffness.

    Science.gov (United States)

    Hayashi, Koichiro; Maeda, Seiji; Iemitsu, Motoyuki; Otsuki, Takeshi; Sugawara, Jun; Tanabe, Takumi; Miyauchi, Takashi; Kuno, Shinya; Ajisaka, Ryuichi; Matsuda, Mitsuo

    2008-02-01

    Arterial stiffness, an independent risk factor for cardiovascular disease, increases with advancing age. Arterial stiffness is improved by regular exercise, but individual responses to exercise training are variable. Given that estrogen and estrogen receptor-alpha (ER-alpha) can induce vasodilation and can exert an antiatherosclerotic effect in vessels, we hypothesized that gene polymorphisms of ER-alpha might influence the ability of regular exercise to improve arterial stiffness in postmenopausal women. One hundred ninety-five healthy postmenopausal women (62 +/- 6 yr, mean +/- SD) participated in our cross-sectional study. We determined the genotype of single-nucleotide polymorphisms (SNP) at -401T/C of intron 1 of the ER-alpha gene. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV), and daily physical activity was estimated by a uniaxial accelerometer. Subjects were divided into active and inactive groups according to the median value (200 kcal.d(-1)) of energy expenditure. baPWV in individuals with the TT variant of -401T/C genotype were significantly higher than for individuals with the TC+CC genotype. No significant differences in mean baPWV values were found between the active group and the inactive group (P = 0.09). A significant reduction of baPWV secondary to increased daily physical activity was observed in individuals with the TC+CC genotype but not in individuals with the TT genotype (TT/active: 1470 +/- 36 cm.s(-1); TT/inactive: 1457 +/- 34 cm.s(-1); TC+CC/active: 1359 +/- 21 cm.s(-1); TC+CC/inactive: 1433 +/- 24 cm.s(-1)). These results suggest that ER-alpha polymorphism affects the regular exercise-related reduction in arterial stiffness in healthy postmenopausal women.

  5. Dopamine Transporter Genotype Conveys Familial Risk of Attention-Deficit/Hyperactivity Disorder through Striatal Activation

    Science.gov (United States)

    Durston, Sarah; Fossella, John A.; Mulder, Martijn J.; Casey B. J.; Ziermans, Tim B.; Vessaz, M. Nathalie; Van Engeland, Herman

    2008-01-01

    The study examines the effect of the dopamine transporter (DAT1) genotype in attention-deficit/hyperactivity disorder (ADHD). The results confirm that DAT1 translates the genetic risk of ADHD through striatal activation.

  6. Dopamine Transporter Genotype Conveys Familial Risk of Attention-Deficit/Hyperactivity Disorder through Striatal Activation

    Science.gov (United States)

    Durston, Sarah; Fossella, John A.; Mulder, Martijn J.; Casey B. J.; Ziermans, Tim B.; Vessaz, M. Nathalie; Van Engeland, Herman

    2008-01-01

    The study examines the effect of the dopamine transporter (DAT1) genotype in attention-deficit/hyperactivity disorder (ADHD). The results confirm that DAT1 translates the genetic risk of ADHD through striatal activation.

  7. Strict blood pressure control associates with decreased mortality risk by APOL1 genotype.

    Science.gov (United States)

    Ku, Elaine; Lipkowitz, Michael S; Appel, Lawrence J; Parsa, Afshin; Gassman, Jennifer; Glidden, David V; Smogorzewski, Miroslaw; Hsu, Chi-Yuan

    2017-02-01

    Although APOL1 high-risk genotype partially accounts for the increased susceptibility of blacks to chronic kidney disease (CKD), whether APOL1 associates differentially with mortality risk remains controversial. Here we evaluate the association between APOL1 genotype and risk of death and determine whether APOL1 status modifies the association between strict versus usual blood pressure control and mortality risk. We performed a retrospective analysis of the African American Study of Kidney Disease and Hypertension trial that randomized black participants with CKD to strict versus usual blood pressure control from 1995 to 2001. This included 682 participants with known APOL1 genotype (157 with high-risk genotype) previously assigned to either strict (mean arterial pressure [MAP] 92 mm Hg or less) versus usual blood pressure control (MAP 102-107 mm Hg) during the trial. During a median follow-up of 14.5 years, risk of death did not differ between individuals with high- versus low-risk APOL1 genotypes (unadjusted hazard ratio 1.00 [95% confidence interval 0.76-1.33]). However, a significant interaction was detected between the APOL1 risk group and blood pressure control strategy. In the APOL1 high-risk group, the risk of death was 42% lower comparing strict versus usual blood pressure control (0.58 [0.35-0.97]). In the APOL1 low-risk group, the risk of death comparing strict versus usual blood pressure control was not significantly different (1.09 [0.84-1.43]). Thus, strict blood pressure control during CKD associates with a lower risk of death in blacks with the high-risk CKD APOL1 genotype. Knowledge of APOL1 status could inform selection of blood pressure treatment targets in black CKD patients. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  8. TGF-alpha genotypes, oral clefts, and environmental risk factors: A population-based California study

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, G.M.; Wasserman, C.R. [CA Birth Defects Monitoring Program, Emeryville, CA (United States); Lammer, E.J. [Stanford Univ., Palo Alto, CA (United States)] [and others

    1994-09-01

    Several studies have shown a relation between genetic variation at the TGF-alpha locus and oral clefts. These studies had limited sample sizes and also lacked data on additional factors potentially related to clefting. We investigated the influence on clefting from risk factors, such as maternal smoking, dependent on TFG-alpha genotype. This was accomplished using a large population-bases case-control study of fetuses and liveborn infants with oral clefts among a 1987-89 cohort of California births (N=548,844). To obtain data on potential risk factors, telephone interviews were conducted with mothers of 731 (84.5% of eligible) cleft cases, and 734 (78.2%) nonmalformed controls. DNA was obtained from newborn screening bloodspots and genotyped by using SSCP designed to detect the Taq1 RFLP. Among mothers who completed an interview, genotyping results were available for 571 (78.1%) cases and 640 (87.2%) controls. Compared to controls, the risk estimate for TGF-alpha polymorphism as measured by the odds ratio was: 0.99 (95% confidence interval 0.64, 1.5) for isolated cleft lip {plus_minus}palate; 0.88 (0.33, 2.2) for nonisolated cleft lip {plus_minus}palate; 1.6 (0.94, 2.8) for isolated cleft palate; 1.9 (0.82, 4.3) for nonisolated cleft palate; and 2.2 (0.99, 5.0) for clefts with known etiology. This dataset also revealed 1.4 to 2-fold increased risks for maternal cigarette smoking > 19 cigs/day in early pregnancy. Among these heavy smokers, risk of clefting was even more increased for infants with the TGF-alpha polymorphism. Our data suggest an association between the TGF-alpha uncommon allele and some phenotypic subgroups as well as provide evidence for a genetic-environment interaction between maternal smoking and the variant in the etiology of clefting. The fraction of cases possibly attributed to this interaction, however, was small.

  9. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk.

    Science.gov (United States)

    Walsh, Kyle M; Codd, Veryan; Rice, Terri; Nelson, Christopher P; Smirnov, Ivan V; McCoy, Lucie S; Hansen, Helen M; Elhauge, Edward; Ojha, Juhi; Francis, Stephen S; Madsen, Nils R; Bracci, Paige M; Pico, Alexander R; Molinaro, Annette M; Tihan, Tarik; Berger, Mitchel S; Chang, Susan M; Prados, Michael D; Jenkins, Robert B; Wiemels, Joseph L; Samani, Nilesh J; Wiencke, John K; Wrensch, Margaret R

    2015-12-15

    Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82x10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48x10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83x10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis.

  10. Television food advertisement exposure and FTO rs9939609 genotype in relation to excess consumption in children.

    Science.gov (United States)

    Gilbert-Diamond, D; Emond, J A; Lansigan, R K; Rapuano, K M; Kelley, W M; Heatherton, T F; Sargent, J D

    2017-01-01

    Exposure to food advertisements may cue overeating among children, especially among those genetically predisposed to respond to food cues. We aimed to assess how television food advertisements affect eating in the absence of hunger among children in a randomized trial. We hypothesized that the fat mass and obesity-associated gene (FTO) rs9939609 single-nucleotide polymorphism would modify the effect of food advertisements. In this randomized experiment, 200 children aged 9-10 years were served a standardized lunch and then shown a 34-min television show embedded with either food or toy advertisements. Children were provided with snack food to consume ad libitum while watching the show and we measured caloric intake. Children were genotyped for rs9939609 and analyses were conducted in the overall sample and stratified by genotype. A formal test for interaction of the food advertisement effect on consumption by rs9939609 was conducted. About 172 unrelated participants were included in this analysis. Children consumed on average 453 (s.d.=185) kcals during lunch and 482 (s.d.=274) kcals during the experimental exposure. Children who viewed food advertisements consumed an average of 48 kcals (95% confidence interval: 10, 85; P=0.01) more of a recently advertised food than those who viewed toy advertisements. There was a statistically significant interaction between genotype and food advertisement condition (P for interaction=0.02), where the difference in consumption of a recently advertised food related to food advertisement exposure increased linearly with each additional FTO risk allele, even after controlling for body mass index percentile. Food advertisement exposure was associated with greater caloric consumption of a recently advertised food, and this effect was modified by an FTO genotype. Future research is needed to understand the neurological mechanism underlying these associations.

  11. Most common genotypes and risk factors for HCV in Gaza strip: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Abu-Jadallah Salah Y

    2009-07-01

    Full Text Available Abstract Background The present work aims at determining HCV genotypes in patients with chronic HCV infection, in Gaza strip, Palestine. The most common risk factors for HCV transmission were also evaluated in conjunction with the genotyping data. Results The study shows that there are only two major genotypes of HCV in Gaza Strip: Genotype 1 (subtypes 1a and 1b collectively contribute to 28.3% of the cases, and genotype 4 (subtypes 4a and 4c/d collectively contribute to 64.1% of the cases. Mixed infection with the two genotypes was also present among 7.6% of the cases. In this study a statistically significant relationship was established between the distribution of these genotypes and the patients' living place, traveling history, history of blood transfusion and history of surgical operations. Conclusion The present study is the first to link HCV genotyping in Gaza strip with its possible roots of transmission. Traveling to endemic countries, especially Egypt; blood transfusion and surgical operations are major roots of HCV infection in Gaza strip. The results indicate that iatrogenic and nosocomial procedures may be responsible for the majority of HCV infections in Gaza strip.

  12. Changes in lifestyle and total homocysteine in relation to MTHFR (C677T) genotype: the Inter99 study

    DEFF Research Database (Denmark)

    Husemoen, LL; Thomsen, TF; Fenger, M;

    2006-01-01

    , changes in tHcy did not differ between participants randomized to low- and high-intensity lifestyle intervention. However, the MTHFR TT genotype was associated with a significant decrease in tHcy compared with the CC/CT genotype in which an increase was observed. In addition, changes in tHcy were...... associated with changes in several of the biological CVD risk markers: weight, total cholesterol, HDL cholesterol, LDL cholesterol and systolic blood pressure. CONCLUSIONS: Our results indicate that tHcy may not be reduced by lifestyle changes; additionally, they suggest that tHcy may be related...

  13. Cancer risk and genotype-phenotype correlations in PTEN hamartoma tumor syndrome

    NARCIS (Netherlands)

    Nieuwenhuis, M.H.; Kets, C.M.; Murphy-Ryan, M.; Yntema, H.G.; Evans, D.G.; Colas, C.; Moller, P.; Hes, F.J.; Hodgson, S.V.; Olderode-Berends, M.J.; Aretz, S.; Heinimann, K.; Garcia, E.B.; Douglas, F.; Spigelman, A.; Timshel, S.; Lindor, N.M.; Vasen, H.F.

    2014-01-01

    Patients with germline PTEN mutations are at high risk of developing benign and malignant tumours. We aimed to evaluate the cumulative risk of several types of cancer and of dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease, LDD). In addition, genotype-phenotype correlations in PTEN hama

  14. War exposure, 5-HTTLPR genotype and lifetime risk of depression

    Science.gov (United States)

    Artero, Sylvaine; Touchon, Jacques; Dupuy, Anne-Marie; Malafosse, Alain; Ritchie, Karen

    2011-01-01

    Background in 1962, during the Algerian war, approximately one and a half million French people living in Algeria were repatriated to France in very poor and often life-threatening conditions. These subjects constitute a cohort for the study of the long term impact of gene-environment interaction on depression. Aims To examine the interaction between a highly stressful life event and subsequent depression, and its modulation by the serotonin transporter gene (5-HTTLPR). Method A community sample of elderly persons aged 65 years and over residing in the Montpellier region of the South of France was randomly recruited from electoral rolls. Genotyping was performed on 248 repatriated persons and 632 controls. Current and lifetime major and minor depressions were assessed according to DSM-IV criteria. Results A significant relationship was observed between exposure to repatriation and subsequent depression (pwar repatriation is significantly modulated by 5-HTTLPR genotype but this appears to occur only in persons who were younger at the time of exposure. PMID:21593514

  15. Prevalence and genotyping of high risk human papillomavirus in cervical cancer samples from Punjab, Pakistan.

    Science.gov (United States)

    Siddiqa, Abida; Zainab, Maidah; Qadri, Ishtiaq; Bhatti, Muhammad Faraz; Parish, Joanna L

    2014-07-17

    Cervical cancer is the third most common cause of cancer-related death in women worldwide. Infection with high-risk human papillomavirus (HPV) is established as the cause of cervical carcinoma, therefore, high risk HPV detection may have prognostic significance for the women who are at increased risk of disease progression. The paucity of data on the incidence of cervical cancer in Pakistan makes it difficult to determine disease burden. Even less information is available regarding the prevalent HPV strains in cervical specimens collected from this region. Cervical cancer is a neglected disease in Pakistan in terms of screening, prevention, and vaccination. Identification and accurate genotyping of the virus burden in cancer specimens is important to inform intervention policies for future management of HPV associated disease and to potentially stratify patients dependent on HPV status. In this study, detection and genotyping of HPV types 16 and 18 from 77 cervical specimens were carried out. Consensus primers GP5+/GP6+, which detect 44 genital HPV types, and type specific primers (TS16 and TS18) were used in conjunction with newly designed type specific primers. Using a combination of these methods of detection, a total of 94.81% (95% CI ±4.95) of cervical lesions were positive for HPV. Single infections of HPV16 were detected in 24.68% (95% CI ±9.63) of total samples and HPV18 was found in 25.97% (95% CI ±9.79) samples. Interestingly, a high proportion of samples (40.26%, 95% CI ±10.95) was positive for both HPV16 and 18, indicating a higher incidence of co-infection than previously reported for similar ethnic regions. The HPV genotype of 3.90% of HPV positive samples remained undetected, although these samples were positive with the GP5+/GP6+ primer set indicating infection with an HPV type other than 16 or 18. These data indicate that the overall incidence of high risk HPV infection in cervical cancer and intraepithelial neoplasia specimens in Punjab

  16. Triad of Risk for Late Onset Alzheimer’s: Mitochondrial Haplotype, APOE Genotype and Chromosomal Sex

    Science.gov (United States)

    Wang, Yiwei; Brinton, Roberta D.

    2016-01-01

    Brain is the most energetically demanding organ of the body, and is thus vulnerable to even modest decline in ATP generation. Multiple neurodegenerative diseases are associated with decline in mitochondrial function, e.g., Alzheimer’s, Parkinson’s, multiple sclerosis and multiple neuropathies. Genetic variances in the mitochondrial genome can modify bioenergetic and respiratory phenotypes, at both the cellular and system biology levels. Mitochondrial haplotype can be a key driver of mitochondrial efficiency. Herein, we focus on the association between mitochondrial haplotype and risk of late onset Alzheimer’s disease (LOAD). Evidence for the association of mitochondrial genetic variances/haplotypes and the risk of developing LOAD are explored and discussed. Further, we provide a conceptual framework that suggests an interaction between mitochondrial haplotypes and two demonstrated risk factors for Alzheimer’s disease (AD), apolipoprotein E (APOE) genotype and chromosomal sex. We posit herein that mitochondrial haplotype, and hence respiratory capacity, plays a key role in determining risk of LOAD and other age-associated neurodegenerative diseases. Further, therapeutic design and targeting that involve mitochondrial haplotype would advance precision medicine for AD and other age related neurodegenerative diseases.

  17. Easy and fast detection and genotyping of high-risk human papillomavirus by dedicated DNA microarrays.

    Science.gov (United States)

    Albrecht, Valérie; Chevallier, Anne; Magnone, Virginie; Barbry, Pascal; Vandenbos, Fanny; Bongain, André; Lefebvre, Jean-Claude; Giordanengo, Valérie

    2006-11-01

    Persistent cervical high-risk human papillomavirus (HPV) infection is correlated with an increased risk of developing a high-grade cervical intraepithelial lesion. A two-step method was developed for detection and genotyping of high-risk HPV. DNA was firstly amplified by asymmetrical PCR in the presence of Cy3-labelled primers and dUTP. Labelled DNA was then genotyped using DNA microarray hybridization. The current study evaluated the technical efficacy of laboratory-designed HPV DNA microarrays for high-risk HPV genotyping on 57 malignant and non-malignant cervical smears. The approach was evaluated for a broad range of cytological samples: high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of high-grade (ASC-H). High-risk HPV was also detected in six atypical squamous cells of undetermined significance (ASC-US) samples; among them only one cervical specimen was found uninfected, associated with no histological lesion. The HPV oligonucleotide DNA microarray genotyping detected 36 infections with a single high-risk HPV type and 5 multiple infections with several high-risk types. Taken together, these results demonstrate the sensitivity and specificity of the HPV DNA microarray approach. This approach could improve clinical management of patients with cervical cytological abnormalities.

  18. Postmortem Changes in Pork Muscle Protein Phosphorylation in Relation to the RN Genotype

    DEFF Research Database (Denmark)

    Lametsch, René; Larsen, Martin Røssel; Essén-Gustavsson, Birgitta

    2011-01-01

    Postmortem changes in pork muscle protein phosphorylation in relation to the RN(-) genotype were investigated using one-dimensional gel electrophoresis and a phosphor specific staining. The phosphorylation levels of several protein bands were found to be affected by the RN(-) genotype and to chan...

  19. The contributions of the tissue inhibitor of metalloproteinase-1 genotypes to triple negative breast cancer risk.

    Science.gov (United States)

    Chang, Wen-Shin; Liu, Liang-Chih; Hsiao, Chieh-Lun; Su, Chen-Hsien; Wang, Hwei-Chung; Ji, Hong-Xue; Tsai, Chia-Wen; Maa, Ming-Chei; Bau, Da-Tian

    2016-03-01

    The tissue inhibitors of metalloproteinases (TIMPs) are a family of multifunctional proteins which have been shown to be upregulated in various types of cancers. However, the contribution of TIMPs in breast cancer is not fully understood, not to mention triple negative breast cancer (TNBC). This study's aim was to evaluate the contribution of TIMP-1 rs4898, rs6609533, and rs2070584 genotypes to the risk of breast cancer, especially the subtype of TNBC. The contributions of these TIMP-1 genotypes to cancer risk were examined among 1232 breast cancer patients and 1232 healthy controls, and several clinicopathologic factors were also analyzed. The results showed that the percentages of CC, CT, and TT of TIMP-1 rs4898 were differentially distributed at 28.5%, 33.1% and 38.4% in the breast cancer patient group and 34.5%, 41.0% and 24.5% in the control group, respectively (P for trend = 7.99*10(-13)). It was also found that the CC genotype carriers were of increased risk for breast cancer (odds ratio = 1.90, 95% confidence interval = 1.55-2.33, P = 0.0001) than the TT genotype carriers. In addition, we analyzed the allelic frequency distributions of all three TIMP-1s, and the results showed that the C allele of TIMP-1 rs4898 contributes to an increase in breast cancer susceptibility (P = 2.41*10(-12)). On the other hand, there was no difference found in the distribution of genotypic or allelic frequencies among the patients and the controls for TIMP-1 rs6609533 and rs2070584. Thus, it is our conclusion that the CC genotype of TIMP-1 rs4898 compared to the TT wild-type genotype may increase the risk for breast cancer, especially TNBC in Taiwan, and may serve as an early detective and predictive marker.

  20. Study of Agro-Physiological Charactristics Related to Drought Tolerance in Advanced Durum Genotypes

    Directory of Open Access Journals (Sweden)

    R. Mohammadi

    2011-01-01

    Full Text Available Abstract This study was conducted with 18 advanced durum genotypes and two check cultivars, Zardak (durum check and Sardari (Bread wheat check, under rainfed and supplemental irrigation in field and also under stress (polyethylene glycol and non-stress (distilled water conditions in laboratory in Sararood station during growing seasons 2004-5 and 2005-6. The genotypes were significantly varied based on analysis of variance and mean comparison for the studied agro-physiologic traits. In the both growing seasons, the genotypes No. 9, 15 and 19 had the highest grain yield under rain-fed condition. Tthe genotypes No. 13 and 16 for 2004-05 and the genotypes No. 8, 12 and 19 for 2005-06 had the highest grain yield performance under supplemental irrigation. The genotype No-16 with the highest yield across environments had the highest STI and TOL, whereas the genotype No. 8 with the lowest yield had the lowest TOL and relatively low STI. The results of path-coefficient analysis for grain yield under rain-fed condition showed that the traits of DHE, DM, FL, Ped.L/PLH, PLH, RWC, SL had positive direct effect on yield and the others traits had negative direct effect. The genotype No. 19 had the highest coleoptile and rootlet length and for these two traits genotypes No. 6 and 17 were in lowest. The genotype No. 19 had the highest PIS and PIN and genotype No. 3 had the lowest. The genotypes No. 3, 9, 11, 14 and 20 had the higher GSI under stress than non-stress conditions. The STI as a field criterion had significant positive correlation with the traits of Root.L. and Root. No., which indicating selection based on Root. L. and Root.No. in laboratory condition may be useful and recommended for screening in field condition. Keywords: Durum wheat, Agro-physiological traits, STI, GSI

  1. Genotype × environment interaction effects on early fresh storage root yield and related traits in cassava

    Institute of Scientific and Technical Information of China (English)

    Robooni; Tumuhimbise; Rob; Melis; Paul; Shanahan; Robert; Kawuki

    2014-01-01

    Cassava(Manihot esculenta Crantz) is an important root crop worldwide. It exhibits substantial differential genotypic responses to varying environmental conditions, a phenomenon termed genotype × environment interaction(GEI). A significant GEI presents challenges in the selection of superior genotypes. The objective of this study was to examine the effect of genotype,environment and GEI on early fresh storage root yield(FSRY) and related traits in cassava.Accordingly, 12 cassava genotypes were evaluated in a randomised complete block design at three contrasting locations(Jinja, Nakasongola and Namulonge) in Uganda. Trials were harvested nine months after planting and the data collected were analysed using the additive main effects and multiplicative interaction(AMMI) model. The AMMI analysis of variance showed significant variation among genotypes for early FSRY and all other traits assessed.Locations were significantly different for all traits except for cassava brown streak disease root necrosis. The GEI effect was non-significant for early FSRY, but significant for other traits. For early FSRY, 48.5% of the treatment sum of squares was attributable to genotypes, 27.3% to environments, and 24.1% to GEI, indicating a predominance of genotypic variation for this trait.Predominance of genotypic variation was also observed for all the other traits. A majority of the genotypes(67%) had low interaction effects with locations for early FSRY, with Akena, CT2, CT4 and NASE14 being the most stable genotypes for the trait. Significant negative correlation was observed between cassava mosaic disease severity and early FSRY and storage root number,indicating significant negative effects of cassava mosaic disease on early FSRY and stability in cassava. The information generated will inform future selection initiatives for superior early-yielding cassava genotypes combining resistance to cassava mosaic and brown streak diseases in Uganda.

  2. Genotype × environment interaction effects on early fresh storage root yield and related traits in cassava

    Directory of Open Access Journals (Sweden)

    Robooni Tumuhimbise

    2014-10-01

    Full Text Available Cassava (Manihot esculenta Crantz is an important root crop worldwide. It exhibits substantial differential genotypic responses to varying environmental conditions, a phenomenon termed genotype × environment interaction (GEI. A significant GEI presents challenges in the selection of superior genotypes. The objective of this study was to examine the effect of genotype, environment and GEI on early fresh storage root yield (FSRY and related traits in cassava. Accordingly, 12 cassava genotypes were evaluated in a randomised complete block design at three contrasting locations (Jinja, Nakasongola and Namulonge in Uganda. Trials were harvested nine months after planting and the data collected were analysed using the additive main effects and multiplicative interaction (AMMI model. The AMMI analysis of variance showed significant variation among genotypes for early FSRY and all other traits assessed. Locations were significantly different for all traits except for cassava brown streak disease root necrosis. The GEI effect was non-significant for early FSRY, but significant for other traits. For early FSRY, 48.5% of the treatment sum of squares was attributable to genotypes, 27.3% to environments, and 24.1% to GEI, indicating a predominance of genotypic variation for this trait. Predominance of genotypic variation was also observed for all the other traits. A majority of the genotypes (67% had low interaction effects with locations for early FSRY, with Akena, CT2, CT4 and NASE14 being the most stable genotypes for the trait. Significant negative correlation was observed between cassava mosaic disease severity and early FSRY and storage root number, indicating significant negative effects of cassava mosaic disease on early FSRY and stability in cassava. The information generated will inform future selection initiatives for superior early-yielding cassava genotypes combining resistance to cassava mosaic and brown streak diseases in Uganda.

  3. Prevalence and Distribution of High-Risk Genotypes of HPV in Women with Severe Cervical Lesions in Madrid, Spain: Importance of Detecting Genotype 16 and Other High-Risk Genotypes.

    Science.gov (United States)

    Mateos Lindemann, Maria Luisa; Sánchez Calvo, Juan Manuel; Chacón de Antonio, Jesús; Sanz, Itziar; Diaz, Esperanza; Rubio, Maria Dolores; de la Morena, Maria Luisa

    2011-01-01

    Background. Persistent infection with high-risk human papillomavirus (HR-HPV) has been demonstrated to be the necessary causal factor for developing cervical cancer. To know the most prevalent HR-HPV in different geographical areas is important to design diagnostic tests and implementation of vaccines. Objectives. The goal of this study is to evaluate the prevalence of HR-HPV in a total of 1001 patients, 198 with normal cytology results, 498 with low-grade squamous intraepithelial lesion (LSIL), and 205 with high-grade squamous intraepithelial lesion (HSIL) who attended our gynaecology department for opportunistic screening of HPV infection. Study design. Cervical samples were taken in a PreservCyt vial (Cytyc Corporation, Boxborough, MA). Hybrid capture assay was carried out following the manufacturer's instructions (Digene Corp., Gaithersburg, MD). All samples were further studied with polymerase chain reaction (PCR) (Linear Array HPV Genotyping Test, Roche Diagnostics, Mannheim, Germany). Results. Genotype 16 was the most prevalent HR-HPV in the three groups, 17.8% in the patients with normal cytology results, 22.3% in the LSIL group, and 60% in the HSIL group. Genotype 18 had a very low prevalence in all groups. Other HR-HPV genotypes such as genotype 31, genotype 58 and genotype 52 were found in significant numbers in HSIL patients. Discussion. Our data show that genotypes 16, 31, 58, and 52 are the most prevalent HR-HPV in cervical samples with severe intraepithelial lesion in Spain. There may be some geographical variation in prevalence of carcinogenic types, and it must be considered for designing diagnostic tests and vaccine.

  4. Changes in lifestyle and total homocysteine in relation to MTHFR (C677T) genotype: the Inter99 study

    DEFF Research Database (Denmark)

    Husemoen, LL; Thomsen, TF; Fenger, M

    2006-01-01

    BACKGROUND: Reduction in total homocysteine (tHcy) may be clinically relevant in the prevention of cardiovascular disease (CVD) in the general population. OBJECTIVE: To examine the effects of changes in various lifestyle habits and lifestyle related biological CVD risk markers on changes in t......Hcy in relation to MTHFR(C677T) genotype. DESIGN: A 1 year follow-up study. SETTING: Copenhagen County, Denmark. SUBJECTS: Statistical analyses were based on a population-based sample of 915 men and women aged 30-60 years assessed to be at increased CVD risk at baseline and therefore offered lifestyle...... intervention and re-examination after one year. RESULTS: None of the studied lifestyle changes-- smoking, physical activity, dietary habits, and coffee, tea, and alcohol consumption-- was significantly associated with changes in tHcy, either overall, or in any of the MTHFR genotype subgroups. In addition...

  5. Hepatitis B virus infection profile in hemodialysis patients in Central Brazil: prevalence, risk factors, and genotypes

    Directory of Open Access Journals (Sweden)

    Renata C Ferreira

    2006-09-01

    Full Text Available Hemodialysis patients are at high risk for hepatitis B virus (HBV infection. A survey was conducted in the hemodialysis population of the state of Goiás, Central Brazil, aiming to assess the prevalence of HBV infection, to analyse associated risk factors, and also to investigate HBV genotypes distribution. A total of 1095 patients were interviewed in 15 dialysis units. Serum samples were screened for HBV serological markers by enzyme-linked immunosorbent assay. Hepatitis B surface antigen (HBsAg positive samples were tested for HBV DNA by polymerase chain reaction and genotyped by restriction fragment length polymorphism. Global HBV infection prevalence was 29.8% (95% CI: 27.1-32.5. Multivariate analysis of risk factors showed that male gender, length of time on hemodialysis, and blood transfusion before 1993 were associated with HBV positivity. HBV DNA was detected in 65.4% (17/26 of the HBsAg-positive samples. Thirteen of 17 HBV DNA positive samples were genotyped. Genotype D (61.5% was predominant, followed by A (30.8%, while genotype F was detected in only one (7.7% sample.

  6. Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype.

    Directory of Open Access Journals (Sweden)

    Giovanni Frazzetto

    Full Text Available Previous research has reported that a functional polymorphism in the monoamine oxidase A (MAOA gene promoter can moderate the association between early life adversity and increased risk for violence and antisocial behavior. In this study of a combined population of psychiatric outpatients and healthy volunteers (N = 235, we tested the hypothesis that MAOA genotype moderates the association between early traumatic life events (ETLE experienced during the first 15 years of life and the display of physical aggression during adulthood, as assessed by the Aggression Questionnaire. An ANOVA model including gender, exposure to early trauma, and MAOA genotype as between-subjects factors showed significant MAOAxETLE (F(1,227 = 8.20, P = 0.005 and genderxMAOAxETLE (F(1,227 = 7.04, P = 0.009 interaction effects. Physical aggression scores were higher in men who had experienced early traumatic life events and who carried the low MAOA activity allele (MAOA-L. We repeated the analysis in the subgroup of healthy volunteers (N = 145 to exclude that the observed GxE interactions were due to the inclusion of psychiatric patients in our sample and were not generalizable to the population at large. The results for the subgroup of healthy volunteers were identical to those for the entire sample. The cumulative variance in the physical aggression score explained by the ANOVA effects involving the MAOA polymorphism was 6.6% in the entire sample and 12.1% in the sub-sample of healthy volunteers. Our results support the hypothesis that, when combined with exposure to early traumatic life events, low MAOA activity is a significant risk factor for aggressive behavior during adulthood and suggest that the use of dimensional measures focusing on behavioral aspects of aggression may increase the likelihood of detecting significant gene-by-environment interactions in studies of MAOA-related aggression.

  7. Hepatitis B genotypes: Relation to clinical outcome in patients with chronic hepatitis B in Saudi Arabia

    Institute of Scientific and Technical Information of China (English)

    Ayman A Abdo; Badr M Al-Jarallah; Faisal M Sanai; Ahmad S Hersi; Khalid Al-Swat; Nahla A Azzam; Manal Al-Dukhayil; Amira Al-Maarik; Faleh Z Al-Faleh

    2006-01-01

    AIM: To identify the most common hepatitis B virus (HBV)genotype in Saudi Arabia, and correlate the prevailing genotypes with the clinical outcome of patients.METHODS: Patients were consecutively recruited from the hepatology clinics of two tertiary care referral centers. Patients were categorized into 4 different groups:group 1, patients with hepatitis B and normal liver enzymes; group 2, patients with hepatitis B and abnormal liver enzymes but without cirrhosis; group 3, patients with hepatitis B and liver cirrhosis; group 4, patients with hepatitis B and hepatocellular carcinoma. All patients had a positive hepatitis B surface antigen (HBsAg). Genotyping of HBV was performed by nested PCR-mediated amplification of the target sequence and hybridization with sequence-specific oligonucleotides.RESULTS: Seventy patients were enrolled in this study.They were predominantly male (72.9%) in their midforty's (mean age 47 years). Forty-nine (70%) patients were hepatitis B envelope antigen (HBeAg) negative.The majority of patients (64%) acquired HBV through unknown risk factors. Hepatitis B genotyping revealed that 57 patients (81.4%) were genotype D, 1 patient (1.4%) had genotype A, 1 patient (1.4%) had genotype C, and 4 patients (5.7%) had genotype E, while 7 patients (10%) had mixed genotype (4 patients ADG, 1 patient DE, 1 patient DF, and 1 patient ADFG). Based on univariate analysis of genotype D patients, significant predictors of advanced liver disease were age, gender,aspartate transaminase, alanine transaminase, albumin,bilirubin, and alkaline phosphatase (all P < 0.001). In multivariate analysis decreased hemoglobin (r = -0.05;95% CI: -0.08 to -0.03; P = 0.001) and albumin levels (r = -0.004; 95% CI: -0.007 to -0.001; P = 0.002) were highly significant predictors of advanced liver disease.In patients with HBV genotype D, HBeAg negativity was found to increase across advancing stages of liver disease (P = 0.024).CONCLUSION: This study highlights that the vast

  8. Vitamin D status, filaggrin genotype, and cardiovascular risk factors

    DEFF Research Database (Denmark)

    Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Martinussen, Torben

    2013-01-01

    Vitamin D deficiency is associated with increased cardiovascular disease risk in observational studies. Whether these associations are causal is not clear. Loss-of-function mutations in the filaggrin gene result in up to 10% higher serum vitamin D concentrations, supposedly due to a decreased UV......-protection of the keratinocytes. We used a Mendelian randomization approach to estimate the causal effect of vitamin D status on serum lipids, blood pressure, body mass index, waist circumference, and the metabolic syndrome....

  9. Fibrillin-1 genotype and risk of prevalent hypertension

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen; Torp-Pedersen, Christian; Hansen, Tine W;

    2012-01-01

    Objective. Mutations in the fibrillin-1 gene are the cause of Marfan syndrome. We wanted to investigate the relationship between a mutation in this gene and risk of prevalent hypertension. Methods. In a cross-sectional study, the effect of a G-A substitution in intron 27 in the fibrillin-1 gene (rs......11856553) on risk of prevalent hypertension was studied in two large population-based studies: the Health 2006 study, consisting of 3193 women and men, age 18-69 years, and the MONICA10 study, consisting of 2408 women and men, age 41-72 years. In 1646 MONICA10 participants, blood pressure (BP) was also...... measured by 24-h ambulatory recordings. Results. Among the 3193 Health 2006 participants 23 had the G-A variant, and among the 2408 MONICA10 participants 18 had the G-A variant. In Health 2006, the odds ratio estimate (95% confidence intervals) for the G-A variant for risk of hypertension, defined...

  10. Lycopene intake and prostate cancer risk : Effect modification by plasma antioxidants and the XRCC1 genotype

    NARCIS (Netherlands)

    Goodman, Michael; Bostick, Roberd M.; Ward, Kevin C.; Terry, Paul D.; van Gils, Carla H.; Taylor, Jack A.; Mandel, Jack S.

    2006-01-01

    Lycopene has been associated with reduced prostate cancer risk, although the results ofepidemiological studies have varied We hypothesize that an effect of lycopene may be modified by XRCC1 genotype and other antioxidants. We used a food-frequency questionnaire to assess lycopene intake in a case-co

  11. Comparing Human Metapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease

    Science.gov (United States)

    Moe, Nina; Krokstad, Sidsel; Stenseng, Inger Heimdal; Christensen, Andreas; Skanke, Lars Høsøien; Risnes, Kari Ravndal; Nordbø, Svein Arne; Døllner, Henrik

    2017-01-01

    Background It is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV). Methods We prospectively enrolled hospitalized children aged <16 years with LRTI from 2006 to 2015. Children were clinically examined, and nasopharyngeal aspirates were analyzed using semi-quantitative, real-time polymerase chain reaction tests for HMPV, RSV and 17 other pathogens. HMPV-positive samples were genotyped. Results A total of 171 children had HMPV infection. HMPV-infected children with single virus (n = 106) and co-detections (n = 65) had similar clinical manifestations. No clinical differences were found between HMPV genotypes A (n = 67) and B (n = 80). The HMPV-infected children were older (median 17.2 months) than RSV-infected children (median 7.3 months, n = 859). Among single virus-infected children, no differences in age-adjusted LRTI diagnoses were found between HMPV and RSV. Age was an important factor for disease severity among single virus-infected children, where children <6 months old with HMPV had a milder disease than those with RSV, while in children 12–23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age ≥12 months (HMPV), and age <6 months (RSV), prematurity, ≥1 chronic disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease. Conclusions Among hospitalized children with LRTI, HMPV manifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPV- and RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPV- and RSV-infected children. PMID:28095451

  12. Employment relations, flexibility and risk

    DEFF Research Database (Denmark)

    Jensen, Carsten Strøby

    Employment relations literature often distinguishes between social democratic/corporatist models of employment relations and liberal models of employment relations as they are seen as opposite or at least different ways of organizing labor markets. They are often characterized as having very...... different risk profiles in terms of relationships between employees, employers, and the state. Low levels of labor market regulation very often characterize the liberal models of employment relations as we know them from, for instance, the USA and the UK. This means that employment conditions are very often...... insecure and that the burden of unemployment risk mostly lies with the employees rather than the employer. Corporatist – or social democratic – employment relations models are, in contrast to the liberal models, often characterized by stricter regulation of the labor market and by high standards...

  13. CYP1B1 genotype and risk of cardiovascular disease, pulmonary disease, and cancer in 50,000 individuals

    DEFF Research Database (Denmark)

    Kaur-Knudsen, D.; Nordestgaard, B.G.; Tybjaerg-Hansen, A.

    2009-01-01

    associate with risk of myocardial infarction (MI), ischemic heart disease (IHD), ischemic cerebrovascular disease (ICVD), chronic obstructive pulmonary disease (COPD), cancer overall, tobacco-related cancer, and female cancer, possibly dependent on tobacco exposure. METHOD: We genotyped 10 391 adults from....... RESULTS: In the Copenhagen City Heart Study, hazard ratio for MI among never smokers was 1.9 (95% confidence interval: 1.2-3.2) for CYP1B1*3 GG (19%) versus CC (32%). These findings were, however, not confirmed when retested in CGPS and Copenhagen Ischemic Heart Disease Study. For tobacco-related cancer......, we found decreasing risk with CYP1B1*3 CG and GG versus CC; however, this could not be confirmed in the CGPS. For IHD, ICVD, COPD, cancer overall, and female cancer, we found no association with CYP1B1*3 genotype, overall or according to smoking status. For CYP1B1*4 genotype, we did not find any...

  14. Glutathione S-transferases M1, T1 genotypes and the risk of gastric cancer: A case-control study

    Institute of Scientific and Technical Information of China (English)

    Lin Cai; Shun-Zhang Yu; Zuo-Feng Zhang

    2001-01-01

    AIM Glutathione S-transferases (GSTs are involved in the detoxification of many potential carcinogens and appear to play a critical role in the protection from the effects of carcinogens. The contribution of glutathione Stransferases M1 and T1 genotypes to susceptibility to the risk of gastric cancer and their interaction with cigarette smoking are still unclear. The aim of this study was to determine whether there was any relationship between genetic polymorphisms of GSTM1 and GSTT1 and gastric cancer. METHODS A population based case - control study was carried out in a high-risk area, Changle County, Fujian Province, China. The epidemiological data were collected by a standard questionnaire and blood samples were obtained from 95 incidence gastric cancer cases and 94 healthy controls. A polymerase chain reaction method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA. Logistic regression model was employed in the data analysis. RESULTS An increase in risk for gastric cancer was found among carriers of GSTM1 null genotype. The adjusted odds ratio (OR) was 2.63 [95% Confidence Interval (95% CI) 1.17-5.88], after controlling for age,gender, cigarette smoking, alcohol drinking, and fish sauce intake. The frequency of GSTT1 null genotype in cancer cases (43.16%) was not significantly different from that in controls (50.00%). However, the risk for gastric cancer in those with GSTM1 null and GSTT1 nonnull genotype was significantly higher than in those with both GSTM1 and GSTT1 non-null genotype (OR = 2.77,95% Cl 1.15- 6.77). Compared with those subjects who never smoked and had normal GSTM1 genotype, Ors were 1.60 (95% CI: 0.62- 4.19) for never smokers with GSTM1 null type, 2.33 (95% CI 0.88- 6.28) for smokers with normal GSTM1, and 8.06 (95% CI 2.83- 23.67) for smokers with GSTM1 null type. CONCLUSIONS GSTM1 gene polymorphisms may be associated with genetic susceptibility of stomach cancer and may modulate tobacco-related

  15. AIDS-related Pneumocystis jirovecii genotypes in French Guiana.

    Science.gov (United States)

    Le Gal, Solène; Blanchet, Denis; Damiani, Céline; Guéguen, Paul; Virmaux, Michèle; Abboud, Philippe; Guillot, Geneviève; Kérangart, Stéphane; Merle, Cédric; Calderon, Enrique; Totet, Anne; Carme, Bernard; Nevez, Gilles

    2015-01-01

    The study described Pneumocystis jirovecii (P. jirovecii) multilocus typing in seven AIDS patients living in French Guiana (Cayenne Hospital) and seven immunosuppressed patients living in Brest, metropolitan France (Brest Hospital). Archival P. jirovecii specimens were examined at the dihydropteroate synthase (DHPS) locus using a PCR-RFLP technique, the internal transcribed spacer (ITS) 1 and ITS 2 and the mitochondrial large subunit rRNA (mtLSUrRNA) gene using PCR and sequencing. Analysis of typing results were combined with an analysis of the literature on P. jirovecii mtLSUrRNA types and ITS haplotypes. A wild DHPS type was identified in six Guianese patients and in seven patients from metropolitan France whereas a DHPS mutant was infected in the remaining Guianese patient. Typing of the two other loci pointed out a high diversity of ITS haplotypes and an average diversity of mtLSUrRNA types in French Guiana with a partial commonality of these haplotypes and types described in metropolitan France and around the world. Combining DHPS, ITS and mtLSU types, 12 different multilocus genotypes (MLGs) were identified, 4 MLGs in Guianese patients and 8 MLGs in Brest patients. MLG analysis allows to discriminate patients in 2 groups according to their geographical origin. Indeed, none of the MLGs identified in the Guianese patients were found in the Brest patients and none of the MLGs identified in the Brest patients were found in the Guianese patients. These results show that in French Guiana (i) PCP involving DHPS mutants occur, (ii) there is a diversity of ITS and mtLSUrRNA types and (iii) although partial type commonality in this territory and metropolitan France can be observed, MLG analysis suggests that P. jirovecii organisms from French Guiana may present specific characteristics.

  16. Large-scale genotyping identifies 41 new loci associated with breast cancer risk

    Science.gov (United States)

    Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna; Ghoussaini, Maya; Dennis, Joe; Milne, Roger L; Schmidt, Marjanka K; Chang-Claude, Jenny; Bojesen, Stig E; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Lee, Andrew; Turnbull, Clare; Rahman, Nazneen; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Silva, Isabel dos Santos; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Hopper, John L; Southey, Melissa C; Makalic, Enes; Schmidt, Daniel F; Uitterlinden, Andre G; Hofman, Albert; Hunter, David J; Chanock, Stephen J; Vincent, Daniel; Bacot, François; Tessier, Daniel C; Canisius, Sander; Wessels, Lodewyk F A; Haiman, Christopher A; Shah, Mitul; Luben, Robert; Brown, Judith; Luccarini, Craig; Schoof, Nils; Humphreys, Keith; Li, Jingmei; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Stevens, Kristen N; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Johnson, Nichola; Aitken, Zoe; Aaltonen, Kirsimari; Heikkinen, Tuomas; Broeks, Annegien; Van’t Veer, Laura J; van der Schoot, C Ellen; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Zamora, M Pilar; Perez, Jose Ignacio Arias; Pita, Guillermo; Alonso, M Rosario; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W R; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Bui, Quang M; Stone, Jennifer; Dite, Gillian S; Apicella, Carmel; Tsimiklis, Helen; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Devilee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline; van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Kristensen, Vessela N; Anton-Culver, Hoda; Slager, Susan; Toland, Amanda E; Edge, Stephen; Fostira, Florentia; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Teo, Soo Hwang; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Sng, Jen-Hwei; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Blot, William J; Signorello, Lisa B; Cai, Qiuyin; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Simard, Jacques; Garcia-Closas, Montse; Pharoah, Paul D P; Chenevix-Trench, Georgia; Dunning, Alison M; Benitez, Javier; Easton, Douglas F

    2013-01-01

    Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ~9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10−8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility. PMID:23535729

  17. Norovirus genotypes implicated in two oyster-related illness outbreaks in Ireland.

    Science.gov (United States)

    Rajko-Nenow, P; Keaveney, S; Flannery, J; McINTYRE, A; Doré, W

    2014-10-01

    We investigated norovirus (NoV) concentrations and genotypes in oyster and faecal samples associated with two separate oyster-related outbreaks of gastroenteritis in Ireland. Quantitative analysis was performed using real-time quantitative reverse transcription polymerase chain reaction and phylogenetic analysis was conducted to establish the NoV genotypes present. For both outbreaks, the NoV concentration in oysters was >1000 genome copies/g digestive tissue and multiple genotypes were identified. In faecal samples, GII.13 was the only genotype detected for outbreak 1, whereas multiple genotypes were detected in outbreak 2 following the application of cloning procedures. While various genotypes were identified in oyster samples, not all were successful in causing infection in consumers. In outbreak 2 NoV GII.1 was identified in all four faecal samples analysed and NoV GII concentrations in faecal samples were >108 copies/g. This study demonstrates that a range of NoV genotypes can be present in highly contaminated oysters responsible for gastroenteritis outbreaks.

  18. Meta-analysis of the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese.

    Science.gov (United States)

    Jin, Bin; Dong, Pin; Li, Keyong; Shen, Bin; Xie, Jin

    2014-01-01

    Glutathione S-transferase T1 (GSTT1) null genotype has been proven to be associated with risks of many cancers. There were also many studies assessing on the association between GSTT1 null genotype and nasopharyngeal carcinoma risk in Chinese, but the findings from those studies were inconsistent. We performed a meta-analysis to provide a more precise assessment on the effect of GSTT1 null genotype on nasopharyngeal carcinoma risk. The PubMed and Wanfang databases were searched to identify eligible case-control studies on the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese. The pooled odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were used to assess the association. Eight case-control studies with a total of 3,702 individuals were finally included in the meta-analysis. Meta-analysis of a total of eight studies showed that GSTT1 null genotype was significantly associated with increased risk of nasopharyngeal carcinoma in Chinese (OR = 2.27; 95% CI 1.41-3.67; P = 0.001). The finding from cumulative meta-analysis showed that there was a trend of more obvious association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese as data accumulated by publication year. Therefore, the GSTT1 null genotype is significantly associated with increased risk of nasopharyngeal carcinoma in Chinese.

  19. Alcohol consumption, alcohol dehydrogenase 1C (ADH1C) genotype, and risk of colorectal cancer in the Netherlands Cohort Study on diet and cancer.

    Science.gov (United States)

    Bongaerts, Brenda W C; de Goeij, Anton F P M; Wouters, Kim A D; van Engeland, Manon; Gottschalk, Ralph W H; Van Schooten, Frederik J; Goldbohm, R Alexandra; van den Brandt, Piet A; Weijenberg, Matty P

    2011-05-01

    Within the Netherlands Cohort Study (1986), we examined associations between alcohol consumption, the alcohol dehydrogenase 1C (ADH1C) genotype, and risk of colorectal cancer (CRC). After a follow-up period of 7.3 years, 594 CRC cases with information on genotype and baseline alcohol intake were available for analyses. Adjusted incidence rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In subjects who reported to have consumed equal amounts of total alcohol both 5 years before baseline and at baseline, drinkers of ≥30g of alcohol per day with the ADH1C*2/*2 genotype were associated-although not statistically significant-with an increased risk of CRC relative to abstainers with the ADH1C*1/*1 genotype (RR: 1.91, 95% CI: 0.68, 5.34). The risk estimate in this exposure group increased slightly when compared with light drinkers of ≥0.5-.05). In subjects who reported to have consumed equal amounts of total alcohol both 5 years before baseline and at baseline, drinkers of ≥30g of alcohol per day were associated-although not statistically significant-with an increased risk of CRC relative to abstainers (RR: 1.38, 95% CI: 0.80, 2.38). This risk estimate for high-level drinkers became stronger when compared with light drinkers (RR: 1.74, 95% CI: 1.01, 2.99). As main effect of genotype, we observed that the ADH1C*2/*2 genotype was associated with a 42% increase in risk of CRC when compared with the ADH1C*1/*1 genotype. In conclusion, both genotype and alcohol consumption were associated with an increased risk of CRC. Owing to limited statistical power, we found no apparent evidence for the ADH1C genotype as effect modifier of the relationship between alcohol intake and CRC. Nevertheless, the interaction deserves further investigation in larger genetic epidemiologic studies. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Can human papillomavirus (HPV) genotyping classify non-16/18 high-risk HPV infection by risk stratification?

    Science.gov (United States)

    Sung, Yeoun Eun; Ki, Eun Young; Lee, Youn Soo; Hur, Soo Young; Lee, Ahwon; Park, Jong Sup

    2016-11-01

    Infection with high-risk genotypes of human papillomavirus (HR-HPV) is the major cause of invasive cervical cancers. HPV-16 and HPV-18 are known to be responsible for two-thirds of all invasive cervical carcinomas, followed by HPV-45, -31, and -33. Current guidelines only differentiate HPV-16/18 (+) by recommending direct colposcopy for treatment. We tried to evaluate whether there are differences in risk among 12 non-16/18 HR-HPV genotypes in this study. The pathology archive database records of 1,102 consecutive gynecologic patients, who had results for cervical cytology and histology and for HPV testing, as determined by HPV 9G DNA chip, were reviewed. Among the 1,102 patients, 346 were non-16/18 HR-HPV (+) and 231 were HPV-16/18 (+). We calculated the odds ratios for ≥cervical intraepithelial neoplasia 2 (CIN 2) of 14 groups of each HR-HPV genotype compared with a group of HR-HPV (-) patients. Based on the odds ratio of each genotype, we divided patients with non-16/18 HR-HPV genotypes (+) into two groups: HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+). The age-adjusted odds ratios for ≥CIN 2 of the HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+) groups compared with a HR-HPV (-) group were 11.9 (95% CI, 7.6 to 18.8; p<0.001) and 2.4 (95% CI, 1.4 to 4.3; p<0.001), respectively, while that of the HPV-16/18 (+) group was 18.1 (95% CI, 11.6 to 28.3; p=0.003). The 12 non-16/18 HR-HPV genotypes can be further categorized (HPV-31/33/35/45/52/58 vs. HPV-39/51/56/59/66/68) by risk stratification. The HPV-31/33/35/45/52/58 genotypes might need more aggressive action. Large scale clinical trials or cohort studies are necessary to confirm our suggestion.

  1. Coat color genotypes and risk and severity of melanoma in gray quarter horses.

    Science.gov (United States)

    Teixeira, R B C; Rendahl, A K; Anderson, S M; Mickelson, J R; Sigler, D; Buchanan, B R; Coleman, R J; McCue, M E

    2013-01-01

    Both graying and melanoma formation in horses have recently been linked to a duplication in the STX17 gene. This duplication, as well as a mutation in the ASIP gene that increases MC1R pathway signaling, affects melanoma risk and severity in gray horses. To determine if melanoma susceptibility in gray Quarter Horses (QH) is lower than gray horses from other breeds because of decreased MC1R signaling resulting from a high incidence of the MC1R chestnut coat color allele in the QH population. A total of 335 gray QH with and without dermal melanomas. Blood or hair root samples were collected from all horses for DNA extraction and genotyping for STX17, ASIP, and MC1R genotypes. Age, sex, and external melanoma presence and grade were recorded. The effect of age and genotype on melanoma presence and severity was evaluated by candidate gene association. Melanoma prevalence (16%) and grade (0.35) in this QH cohort was lower than that reported in other breeds. Age was significantly associated with melanoma prevalence (P = 5.28 × 10(-11)) and severity (P = 2.2 × 10(-13)). No significant effect of MC1R genotype on melanoma prevalence or severity was identified. An effect of ASIP genotype on melanoma risk was not detected. Low STX17 homozygosity precluded evaluation of the gray allele effect. Melanoma prevalence and severity is lower in this population of gray QH than what is reported in other breeds. This could be because of the infrequent STX17 homozygosity, a mitigating effect of the MC1R mutation on ASIP potentiation of melanoma, other genes in the MC1R signaling pathway, or differences in breed genetic background. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  2. Contribution of DNA Repair Xeroderma Pigmentosum Group D Genotypes to Colorectal Cancer Risk in Taiwan.

    Science.gov (United States)

    Chang, Wen-Shin; Yueh, Te-Cheng; Tsai, Chia-Wen; Ji, Hong-Xue; Wu, Cheng-Nan; Wang, Shou-Cheng; Lai, Yi-Liang; Hsu, Shih-Wei; Hsieh, Ming-Hao; Hsiao, Chieh-Lun; Hung, Yi-Wen; Shih, Tzu-Ching; Bau, Da-Tian

    2016-04-01

    It has been previously proposed that genetic variations on DNA repair genes confer susceptibility to cancer and the DNA repair gene Xeroderma Pigmentosum Group D (XPD) is thought to play the role of a helicase during excision repair and transcription. We investigated three genotypes of XPD, at promoter -114 (rs3810366), Asp312Asn (rs1799793) and Lys751Gln (rs13181), regarding their association with colorectal cancer susceptibility in a Taiwanese population. In total, 362 patients with colorectal cancer and 362 gender- and age-matched healthy controls were genotyped by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP), and their XPD genotypes' association with colorectal cancer risk was investigated. The genotypes of XPD Asp312Asn (p=0.2493), Lys751Gln (p=0.7547) and promoter -114 (p=0.8702), were not associated with susceptibility for colorectal cancer. The Chi-square test revealed that the variant alleles of XPD Asp312Asn, Lys751Gln and promoter -114 was not associated with susceptibility for colorectal cancer either [p=0.1330, 0.3888 and 0.8740; odds ratio (OR)=1.20, 0.83 and 0.98; 95% confidence interval (95%CI)=0.95-1.52, 0.54-1.27 and 0.80-1.21, respectively]. The risk of A/G and A/A genotypes have no association with cancer risk among non-alcohol drinkers (OR=1.24, 95%, CI=0.90-1.72, p=0.2103) or alcohol drinkers (OR=1.51, 95% CI=0.64-3.55, p=0.4648). There exists no obvious contribution of XPD genotypes to tumor size (p=0.3531), location (p=0.3006) and lymph node metastasis (p=0.1061). Asp312Asn, Lys751Gln and promoter -114 of the XPD gene were not found to be adequate predictive markers for colorectal cancer risk in Taiwan. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. Molecular Epidemiology Study in Xuanwei: the Relationship among
Coal Type, Genotype and Lung Cancer Risk

    Directory of Open Access Journals (Sweden)

    Jihua LI

    2015-01-01

    Full Text Available Background and objective It has been proven that the lung cancer mortality rate in Xuanwei County, China was among the highest in the country and has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons. This risk may be modified by variation in genetic polymorphisms and coal subtypes. Our objective was to use molecular epidemiological techniques to investigate the relationship among genetic polymorphisms, coal subtype and lung cancer risk in Xuanwei County. Methods On the basis of two population-based case-control studies in residents of Xuanwei County, China, questionnaires covering demographic information, smoking history, family and personal medical history, and information on other variables were administered and buccal cells and sputum samples were collected separately from each subject enrolled to extract DNA. GST superfamily, AKR1C3 superfamily, OGG1 superfamily and other genotype were scanned by useing PCR method. ORs and 95%CIs were used to estimate the association between genotypes, coal subtypes and lung cancer risk factors by conditional Logistic regression using Statistical Analysis Software. Results Compared with subjects who using smokeless coal or wood, smoky coal use was statistically significantly associated with lung cancer risk (OR=7.7, 95%CI: 4.5-13.3. There was marked heterogeneity in risk estimates for specific subtypes of smoky coal. Estimates were highest for coal from the Laibin (OR=24.8, Longtan (OR=11.6 and Baoshan (OR=6.0 coal types, and lower for coal from other types; the risk within the same subtype of coal in male and female were similar. The GSTM1-null genotype, the AKR1C3 (Ex1-70C>G, OGG1 (Ex6-315C>G genotypes were closely associated with increased risk of lung cancer in Xuanwei County, and their odds ratios (95%CI were 2.3 (1.3-4.2, 1.8 (1.0-3.5 and 1.9 (1.1-3.3, respectively. Compared to subjects who with GSTM1-positive and used less than

  4. Alcohol Intake, Myocardial Infarction, Biochemical Risk Factors, and Alcohol Dehydrogenase Genotypes

    DEFF Research Database (Denmark)

    Tolstrup, Janne Schurmann; Grønbæk, Morten; nordestgaard, børge

    2009-01-01

    dehydrogenases. Methods and Results- We used information on 9584 men and women from the Danish general population in the Copenhagen City Heart Study. During follow-up, from 1991 to 2007, 663 incident cases of myocardial infarction occurred. We observed that increasing alcohol intake was associated......  Background- The risk of myocardial infarction is lower among light-to-moderate alcohol drinkers compared with abstainers. We tested associations between alcohol intake and risk of myocardial infarction and risk factors and whether these associations are modified by variations in alcohol...... of myocardial infarction or with any of the cardiovascular biochemical risk factors, and there was no indication that associations between alcohol intake and myocardial infarction and between alcohol intake and risk factors were modified by genotypes. Conclusions- Increasing alcohol intake is associated...

  5. Alcohol intake, myocardial infarction, biochemical risk factors, and alcohol dehydrogenase genotypes

    DEFF Research Database (Denmark)

    Tolstrup, Janne S; Grønbaek, Morten; Nordestgaard, Børge G

    2009-01-01

    dehydrogenases. METHODS AND RESULTS: We used information on 9584 men and women from the Danish general population in the Copenhagen City Heart Study. During follow-up, from 1991 to 2007, 663 incident cases of myocardial infarction occurred. We observed that increasing alcohol intake was associated......BACKGROUND: The risk of myocardial infarction is lower among light-to-moderate alcohol drinkers compared with abstainers. We tested associations between alcohol intake and risk of myocardial infarction and risk factors and whether these associations are modified by variations in alcohol...... of myocardial infarction or with any of the cardiovascular biochemical risk factors, and there was no indication that associations between alcohol intake and myocardial infarction and between alcohol intake and risk factors were modified by genotypes. CONCLUSIONS: Increasing alcohol intake is associated...

  6. Genotype-Environment Correlations for Language-Related Abilities: Implications for Typical and Atypical Learners.

    Science.gov (United States)

    Gilger, Jeffrey W.; Ho, Hsiu-Zu; Whipple, Angela D.; Spitz, Romy

    2001-01-01

    This study examined passive genotype-environment correlations (GECs) for language related abilities by comparing environment-child language associations in adoptive and nonadoptive families. Findings indicate genetic mediation of the association between home environmental variables with children's language-related abilities. Implications for…

  7. Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study

    NARCIS (Netherlands)

    A.J.C. Slooter (Arjen); M. Cruts (Marc); S. Kalmijn (Sandra); M.M.B. Breteler (Monique); C.M. van Duijn (Cock); C. van Broeckhoven (Christine); A. Hofman (Albert)

    1998-01-01

    textabstractOBJECTIVES: To provide risk estimates of dementia and Alzheimer disease as a function of the apolipoprotein E (APOE) genotypes and to assess the proportion of dementia that is attributable to the APOE genotypes. DESIGN: Case-control study nested in a population-based cohort study with a

  8. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk

    NARCIS (Netherlands)

    Thompson, Alexander; Di Angelantonio, Emanuele; Sarwar, Nadeem; Erqou, Sebhat; Saleheen, Danish; Dullaart, Robin P. F.; Keavney, Bernard; Ye, Zheng; Danesh, John

    2008-01-01

    Context The importance of the cholesteryl ester transfer protein (CETP) pathway in coronary disease is uncertain. Study of CETP genotypes can help better understand the relevance of this pathway to lipid metabolism and disease risk. Objective To assess associations of CETP genotypes with CETP

  9. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk

    NARCIS (Netherlands)

    Thompson, Alexander; Di Angelantonio, Emanuele; Sarwar, Nadeem; Erqou, Sebhat; Saleheen, Danish; Dullaart, Robin P. F.; Keavney, Bernard; Ye, Zheng; Danesh, John

    2008-01-01

    Context The importance of the cholesteryl ester transfer protein (CETP) pathway in coronary disease is uncertain. Study of CETP genotypes can help better understand the relevance of this pathway to lipid metabolism and disease risk. Objective To assess associations of CETP genotypes with CETP phenot

  10. Natural history of human papillomavirus infection in non-vaccinated young males: low clearance probability in high-risk genotypes.

    Science.gov (United States)

    Cai, T; Perletti, G; Meacci, F; Magri, V; Verze, P; Palmieri, A; Mazzoli, S; Santi, R; Nesi, G; Mirone, V; Bartoletti, R

    2016-03-01

    In this study, we aimed to investigate the clearance of type-specific genital human papillomavirus (HPV) infection in heterosexual, non-HPV-vaccinated males whose female partners were positive to HPV DNA tests. All consecutive men attending the same sexually transmitted diseases (STD) centre between January 2005 and December 2006 were considered for this study. All subjects (n = 1009) underwent a urologic visit and microbiological tests on first void, midstream urine and total ejaculate samples. One hundred and five patients were positive for HPV DNA (10.4 %; mean age: 34.8 ± 5.8 years) and consented to clinical examination and molecular diagnostic assays for HPV detection scheduled every 6 months (median surveillance period of 53.2 months). HPV genotypes were classified as high risk, probable high risk and low risk. HPV-positive samples which did not hybridise with any of the type-specific probes were referred to as positive non-genotypeable. At enrollment, the distribution of HPV genotypes was as follows: high-risk HPV (n = 37), probable high-risk HPV (n = 6), low-risk HPV (n = 23) and non-genotypeable HPV (n = 39). A high HPV genotype concordance between stable sexual partners emerged (kappa = 0.92; p probable high-risk HPV cases, 20/23 (86.9 %) low-risk HPV cases and 31/39 (79.5 %) non-genotypeable cases. The high-risk HPV genotypes showed the lowest rate and probability of viral clearance (p < 0.001). In our series, high-risk HPV infections were more likely to persist over time when compared with other HPV genotypes.

  11. Content of the cyanogenic glucoside amygdalin in almond seeds related to the bitterness genotype

    Directory of Open Access Journals (Sweden)

    Guillermo Arrázola

    2012-08-01

    Full Text Available Almond kernels can be sweet, slightly bitter or bitter. Bitterness in almond (Prunus dulcis Mill. and other Prunus species is related to the content of the cyanogenic diglucoside amygdalin. When an almond containing amygdalin is chopped, glucose, benzaldehyde (bitter flavor and hydrogen cyanide (which is toxic are released. This two-year-study with 29 different almond cultivars for bitterness was carried out in order to relate the concentration of amygdalin in the kernel with the phenotype (sweet, slightly bitter or bitter and the genotype (homozygous: sweet or bitter or heterozygous: sweet or slightly bitter with an easy analytical test. Results showed that there was a clear difference in the amount of amygdalin between bitter and non-bitter cultivars. However, the content of amygdalin did not differentiate the other genotypes, since similar amounts of amygdalin can be found in the two different genotypes with the same phenotype

  12. GSTM1 null genotype and gastric cancer risk in the Chinese population: an updated meta-analysis and review.

    Science.gov (United States)

    Zhang, Xi-Liang; Cui, Yong-Hui

    2015-01-01

    Although a number of studies have been conducted on the association between the GSTM1 null genotype and gastric cancer in People's Republic of China, this association remains elusive and controversial. To clarify the effects of the GSTM1 null genotype on the risk of gastric cancer, an updated meta-analysis was performed in the Chinese population. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) up to November 5, 2014. A total of 25 studies including 3,491 cases and 5,921 controls were included in this meta-analysis. Overall, a significant association (odds ratio [OR] =1.47, 95% CI: 1.28-1.69) was found between the null GSTM1 and gastric cancer risk when all studies in Chinese population were pooled into the meta-analysis. In subgroup analyses stratified by quality score, geographic area, and source of controls, the same results were observed. Additionally, a significant association was found both in smokers and non-smokers. This meta-analysis showed that the null GSTM1 may be a potential biomarker for gastric cancer risk in Chinese, and further studies with gene-gene and gene-environment interactions are required for definite conclusions.

  13. Effect of GABRA2 genotype on development of incentive-motivation circuitry in a sample enriched for alcoholism risk.

    Science.gov (United States)

    Heitzeg, Mary M; Villafuerte, Sandra; Weiland, Barbara J; Enoch, Mary-Anne; Burmeister, Margit; Zubieta, Jon-Kar; Zucker, Robert A

    2014-12-01

    Heightened reactivity of the incentive-motivation system has been proposed to underlie adolescent-typical risky behaviors, including problem alcohol involvement. However, even in adolescence considerable individual variation in these behaviors exists, which may have genetic underpinnings and be related to variations in risk for later alcohol use disorder (AUD). Variants in GABRA2 have been associated with adult alcohol dependence as well as phenotypic precursors, including impulsiveness and externalizing behaviors. We investigated the impact of GABRA2 on the developmental trajectory of nucleus accumbens (NAcc) activation during anticipation of monetary reward from childhood to young adulthood. Functional MRI during a monetary incentive delay task was collected in 175 participants, with the majority (n = 151) undergoing repeated scanning at 1- to 2-year intervals. One group entered the study at age 8-13 years (n = 76) and another entered at age 18-23 years (n = 99). Most participants were children of alcoholics (79%) and thus at heightened risk for AUD. A total of 473 sessions were completed, covering ages 8-27 years. NAcc activation was heightened during adolescence compared with childhood and young adulthood. GABRA2 genotype (SNP rs279858) was associated with individual differences in NAcc activation specifically during adolescence, with the minor allele (G) associated with greater activation. Furthermore, NAcc activation mediated an effect of genotype on alcohol problems (n = 104). This work demonstrates an impact of GABRA2 genotype on incentive-motivation neurocircuitry in adolescence, with implications for vulnerability to alcoholism. These findings represent an important step toward understanding the genetic and neural basis of individual differences in how risk for addiction unfolds across development.

  14. Hepatitis B virus in Pakistan: A systematic review of prevalence, risk factors, awareness status and genotypes

    Directory of Open Access Journals (Sweden)

    Afzal Samia

    2011-03-01

    Full Text Available Abstract In Pakistan, there are estimated 7-9 million carriers of hepatitis B virus (HBV with a carrier rate of 3-5%. This article reviews the available literature about the prevalence, risk factors, awareness status and genotypes of the HBV in Pakistan by using key words; HBV prevalence, risk factors, awareness status and genotypes in Pakistani population in PubMed, PakMediNet, Directory of Open Access Journals (DOAJ and Google Scholar. One hundred and six different studies published from 1998 to 2010 were included in this study. Weighted mean and standard deviation were determined for each population group. The percentage of hepatitis B virus infection in general population was 4.3318% ± 1.644%, healthy blood donors (3.93% ± 1.58%, military recruits (4.276% ± 1.646%, healthcare persons (3.25% ± 1.202%, pregnant women (5.872% ± 4.984, prisoners (5.75% ± 0.212%, surgical patients (7.397% ± 2.012%, patients with cirrhosis (28.87% ± 11.90%, patients with HCC (22% ± 2.645%, patients with hepatitis (15.896% ± 14.824%, patients with liver diseases (27.54% ± 6.385%, multiple transfused patients (6.223% ± 2.121%, opthalmic patients (3.89% ± 1.004% and users of injectable drugs (14.95% ± 10.536%. Genotype D (63.71% is the most prevalent genotype in Pakistani population. Mass vaccination and awareness programs should be initiated on urgent basis especially in populations with HBV infection rates of more than 5%.

  15. Hepatitis B virus in Pakistan: a systematic review of prevalence, risk factors, awareness status and genotypes.

    Science.gov (United States)

    Ali, Muhammad; Idrees, Muhammad; Ali, Liaqat; Hussain, Abrar; Ur Rehman, Irshad; Saleem, Sana; Afzal, Samia; Butt, Sadia

    2011-03-06

    In Pakistan, there are estimated 7-9 million carriers of hepatitis B virus (HBV) with a carrier rate of 3-5%. This article reviews the available literature about the prevalence, risk factors, awareness status and genotypes of the HBV in Pakistan by using key words; HBV prevalence, risk factors, awareness status and genotypes in Pakistani population in PubMed, PakMediNet, Directory of Open Access Journals (DOAJ) and Google Scholar. One hundred and six different studies published from 1998 to 2010 were included in this study. Weighted mean and standard deviation were determined for each population group. The percentage of hepatitis B virus infection in general population was 4.3318% ± 1.644%, healthy blood donors (3.93% ± 1.58%), military recruits (4.276% ± 1.646%), healthcare persons (3.25% ± 1.202%), pregnant women (5.872% ± 4.984), prisoners (5.75% ± 0.212%), surgical patients (7.397% ± 2.012%), patients with cirrhosis (28.87% ± 11.90%), patients with HCC (22% ± 2.645%), patients with hepatitis (15.896% ± 14.824%), patients with liver diseases (27.54% ± 6.385%), multiple transfused patients (6.223% ± 2.121%), opthalmic patients (3.89% ± 1.004%) and users of injectable drugs (14.95% ± 10.536%). Genotype D (63.71%) is the most prevalent genotype in Pakistani population. Mass vaccination and awareness programs should be initiated on urgent basis especially in populations with HBV infection rates of more than 5%.

  16. Heterogeneity of cag genotypes of Helicobacter pylori in the esophageal mucosa of dyspeptic patients and its relation to histopathological outcomes

    Directory of Open Access Journals (Sweden)

    Monica Contreras

    2014-09-01

    Conclusions: H. pylori may coexist in similar proportions without dominance of one cag genotype, suggesting a heterogeneous distribution in the esophagus. The cagE and virB11 genes can be used as markers of cag-PAI in the esophagus. The single cag-PAI genotype in both mucosae confers an increased risk of developing histological damage.

  17. PrP genotype frequencies and risk evaluation for scrapie in dairy sheep breeds from southern Italy.

    Science.gov (United States)

    Martemucci, Giovanni; Iamartino, Daniela; Blasi, Michele; D'Alessandro, Angela Gabriella

    2015-12-01

    Concerns regarding scrapie in sheep breeding have increased in the last few decades. The present study was carried out in dairy sheep breeds from southern Italy. In order to find breeding animals resistant to scrapie, the PrP genes of 1,205 animals from entire flocks of dairy native Apulian Leccese and Altamurana breeds, and Sicilian Comisana breed, were analysed for polymorphisms at codons 136, 154, and 171 related to scrapie resistance/susceptibility. The Altamurana breed was considered as two populations (Alt-Cav and Alt-Cra-Zoe), based on presumed cross-breeding. A total of five alleles and ten different genotypes were found. The ARQ allele was predominant for all breeds followed by ARR, the most resistant allele to scrapie, which was highly prevalent in Comisana (50%) and in native Alt-Cav (42.4%). The VRQ allele, associated with the highest susceptibility to scrapie, was detected at not negligeable levels in allocthonous Comisana (3.5%), at a low frequency (0.2%) in native Leccese and Alt-Cra-Zoe, while it was absent in Alt-Cav. The frequencies of PrP genotypes with a very low susceptibility risk to scrapie (R1) was higher in Comisana and Alt-Cav. The most susceptible genotype, ARQ/VRQ, was found only in Comisana. Within the Altamurana breed, there were notable differences between Alt-Cav and Alt-Cra-Zoe sheep. The Alt-Cav was characterised by the absence of VRQ and AHQ alleles and by the higher frequency of the ARR/ARR genotype (18.7%). Breeding programs, mainly in endangered breeds such as Altamurana, should be conducted gradually, combining resistance to scrapie, maintenance of genetic variability, and production.

  18. Relation between Endothelial Nitric Oxide Synthase Genotypes and Oxidative Stress Markers in Larynx Cancer

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    K. Yanar

    2016-01-01

    Full Text Available Nitric oxide synthase (eNOS/NOS3 is responsible for the endothelial synthesis of nitric oxide (NO•. G894T polymorphism leads to the amino acid substitution from Glu298Asp that causes lower NOS3 activity and basal NO• production in NOS3 894T (298Asp allele carriers compared with the GG homozygotes. NO• acts as an antioxidant protecting against Fenton’s reaction which generates highly reactive hydroxyl radicals. Allelic variation of NOS3 may influence an individual’s risk of laryngeal cancer (LC. In the current study we have examined the possible relationship between NOS3 G894T genotypes and various systemic oxidative damage markers such as protein carbonyl, advanced oxidation protein products, Cu, Zn-superoxide dismutase, thiol group fractions, and lipid hydroperoxides in LC patients. Genotyping was carried out by PCR-RFLP. In LC patients with TT genotype, Cu, Zn-superoxide dismutase activities and nonprotein thiol levels were significantly higher than the controls. In patients with GT and GG genotype, high levels of lipid hydroperoxides showed statistical significance when compared to controls. Our results indicate a potential relationship among G894T polymorphism of NOS3, and impaired redox homeostasis. Further studies are required to determine the role of NOS3 gene polymorphism and impaired plasma redox homeostasis.

  19. Long-term risk of cervical intraepithelial neoplasia grade 3 or worse according to high-risk human papillomavirus genotype and semi-quantitative viral load among 33,288 women with normal cervical cytology

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian;

    2014-01-01

    In this prospective cohort study, we estimated the long-term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high-risk human papillomavirus (hrHPV) genotype and semi-quantitative viral load at baseline among 33,288 women aged 14-90 years with normal baseline cytology. During...... 2002-2005, residual liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV-tested with Hybrid Capture 2 (HC2) and genotyped with INNO-LiPA. Semi-quantitative viral load was measured by HC2 relative light units in women......HPV genotyping during cervical cancer screening may help identify women at highest risk of CIN3+....

  20. The effect of cigarette smoke and arsenic exposure on urothelial carcinoma risk is modified by glutathione S-transferase M1 gene null genotype

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Huang, Chao-Yuan; Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China)

    2013-01-15

    Inter-individual variation in the metabolism of xenobiotics, caused by factors such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed to evaluate the role of gene–environment interaction in the carcinogenesis of UC. A hospital-based case–control study was conducted. Urinary arsenic profiles were measured using high-performance liquid chromatography–hydride generator-atomic absorption spectrometry. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism technique. Information about cigarette smoking exposure was acquired from a lifestyle questionnaire. Multivariate logistic regression was applied to estimate the UC risk associated with certain risk factors. We found that UC patients had higher urinary levels of total arsenic, higher percentages of inorganic arsenic (InAs%) and monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had significantly increased UC risk. However, no association was observed between gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after adjustment for age and sex. Significant gene–environment interactions among urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and UC risk were observed after adjustment for potential risk factors. Overall, gene–environment interactions simultaneously played an important role in UC carcinogenesis. In the future, large-scale studies should be conducted using tag-SNPs of xenobiotic-metabolism-related enzymes for gene determination. -- Highlights: ► Subjects with GSTM1 null genotype had significantly increased UC risk. ► UC patients had poor arsenic metabolic ability compared to controls. ► GSTM1 null genotype may modify arsenic related UC risk.

  1. The UGT1A6_19_GG genotype is a breast cancer risk factor

    Directory of Open Access Journals (Sweden)

    Christina eJustenhoven

    2013-06-01

    Full Text Available Validation of an association between the UGT1A6_19_T>G (rs6759892 polymorphism and overall breast cancer risk. A pilot study included two population-based case-control studies from Germany (MARIE-GENICA. An independent validation study comprised four independent breast cancer case-control studies from Finland (KBCP, OBCS, Germany (BBCC and Sweden (SASBAC. The pooled analysis included 7,418 cases and 8,720 controls from all six studies. Participants were of European descent. Genotyping was done by MALDI-TOF MS and statistical analysis was performed by logistic regression adjusted for age and study. The increased overall breast cancer risk for women with the UGT1A6_19_GG genotype which was observed in the pilot study was confirmed in the set of four independent study collections (OR 1.13, 95% CI 1.05-1.22; p = 0.001. The pooled study showed a similar effect (OR 1.09, 95% CI 1.04-1.14; p = 0.001. We confirmed the association of UGT1A6_19_GG with increased overall breast cancer risk and conclude that our result from a well powered multi-stage study adds a novel candidate to the panel of validated breast cancer susceptibility loci.

  2. Does Apolipoprotein E genotype affect cardiovascular risk in subjects with acromegaly?

    Science.gov (United States)

    Bozok Cetintas, Vildan; Zengi, Ayhan; Tetik, Asli; Karadeniz, Muammer; Ergonen, Faruk; Kucukaslan, Ali Sahin; Tamsel, Sadik; Kosova, Buket; Sahin, Serap Baydur; Saygılı, Fusun; Eroglu, Zuhal

    2012-06-01

    Acromegaly is a syndrome that results when the pituitary gland produces excess growth hormone after epiphyseal closure at puberty. Usually, subjects with acromegaly exhibit a 2- to 3-fold higher mortality rate from diseases that are associated with cardiovascular complications when compared to the normal population. In this study, we therefore aimed to evaluate whether a well-established cardiovascular risk factor, the Apolipoprotein E (Apo E) genotype, contributes to increased risk of cardiovascular complications in subjects with acromegaly. A total of 102 unrelated acromegaly subjects were prospectively included into this case-control association study and constituted our study group. The study group was comparable by age and gender with 200 unrelated healthy subjects constituting our control group. Genomic DNA was isolated from the peripheral blood leukocytes of all subjects and Apo E genotype (codon 112/158) was assessed by melting temperature analyses after using a real-time PCR protocol. The Apolipoprotein E4 allele was found at a significantly higher frequency in the study group when compared with the control group (P = 0.032). Subjects with the E2 allele, on the other hand, had significantly increased values in body mass index (P = 0.004), waist circumference (P = 0.001), C-reactive protein (CRP) (P acromegaly since it is concurrently present with other cardiovascular risk factors such as the left-side carotid intima media thickness and CRP.

  3. Genotypes of Mycobacterium tuberculosis in patients at risk of drug resistance in Bolivia.

    Science.gov (United States)

    Monteserin, Johana; Camacho, Mirtha; Barrera, Lucía; Palomino, Juan Carlos; Ritacco, Viviana; Martin, Anandi

    2013-07-01

    Bolivia ranks among the 10 Latin American countries with the highest rates of tuberculosis (TB) and multidrug resistant (MDR) TB. In view of this, and of the lacking information on the population structure of Mycobacterium tuberculosis in the country, we explored genotype associations with drug resistance and clustering by analyzing isolates collected in 2010 from 100 consecutive TB patients at risk of drug resistance in seven of the nine departments in which Bolivia is divided. Fourteen isolates were MDR, 29 had other drug resistance profiles, and 57 were pansusceptible. Spoligotype family distribution was: Haarlem 39.4%, LAM 26.3%, T 22.2%, S 2.0%, X 1.0%, orphan 9.1%, with very low intra-family diversity and absence of Beijing genotypes. We found 66 different MIRU-VNTR patterns; the most frequent corresponded to Multiple Locus Variable Analysis (MLVA) MtbC15 patterns 860, 372 and 873. Twelve clusters, each with identical MIRU-VNTR and spoligotypes, gathered 35 patients. We found no association of genotype with drug resistant or MDR-TB. Clustering associated with SIT 50 and the H3 subfamily to which it belongs (pBolivia. However, results should be taken cautiously because the sample is small and includes a particular subset of M. tuberculosis population. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Hepatitis C virus in Pakistan: A systematic review of prevalence, genotypes and risk factors

    Institute of Scientific and Technical Information of China (English)

    Yasir Waheed; Talha Shafi; Sher Zaman Safi; Ishtiaq Qadri

    2009-01-01

    In Pakistan more than 10 million people are living with Hepatitis C virus (HCV), with high morbidity and mortality. This article reviews the prevalence,genotypes and factors associated with HCV infection in the Pakistani population. A literature search was performed by using the keywords; HCV prevalence, genotypes and risk factors in a Pakistani population,in Pubmed, PakMediNet and Google scholar. Ninetyone different studies dating from 1994 to May 2009 were included in this study, and weighted mean and standard error of each population group was calculated.Percentage prevalence of HCV was 4.95% ± 0.53% in the general adult population, 1.72% ± 0.24% in the pediatric population and 3.64% ± 0.31% in a young population applying for recruitment, whereas a very high 57% ± 17.7% prevalence was observed in injecting drug users and 48.67% ± 1.75% in a multitransfused population. Most prevalent genotype of HCV was 3a. HCV prevalence was moderate in the general population but very high in injecting drug users and multi-transfused populations. This data suggests that the major contributing factors towards increased HCV prevalence include unchecked blood transfusions and reuse of injection syringes. Awareness programs are required to decrease the future burden of HCV in the Pakistani population.

  5. Association between glutathione S-transferase M1 null genotype and risk of gallbladder cancer: a meta-analysis.

    Science.gov (United States)

    Sun, Hong-Li; Han, Bing; Zhai, Hong-Peng; Cheng, Xin-Hua; Ma, Kai

    2014-01-01

    Glutathione S-transferases (GSTs) are a family of enzymes which are involved in the detoxification of potential carcinogens. Glutathione S-transferase M1 (GSTM1) null genotype can impair the enzyme activity of GSTs and is suspected to increase the susceptibility to gallbladder cancer. Previous studies investigating the association between GSTM1 null genotype and risk of gallbladder cancer reported inconsistent findings. To quantify the association between GSTM1 null genotype and risk of gallbladder cancer, we performed a meta-analysis of published studies. We searched PubMed, Embase, and Wanfang databases for all possible studies. We estimated the pooled odds ratio (OR) with its 95% confidence interval (95% CI) to assess the association. Meta-analysis of total included studies showed that GSTM1 null genotype was not associated with gallbladder cancer risk (OR = 1.13, 95% CI 0.88-1.46, P = 0.332). Subgroup analysis by ethnicity showed that there was no association between GSTM1 null genotype and risk of gallbladder cancer in both Caucasians and Asians. However, meta-analysis of studies with adjusted estimations showed that GSTM1 null genotype was associated with increased risk of gallbladder cancer (OR = 1.46, 95% CI 1.02-2.09, P = 0.038). Thus, this meta-analysis shows that GSTM1 null genotype is likely to be associated with risk of gallbladder cancer. More studies with well design and large sample size are needed to further validate the association between GSTM1 null genotype and gallbladder cancer.

  6. Hepatitis B virus prevalence, risk factors and genotype distribution in HIV infected patients from West Java, Indonesia.

    Science.gov (United States)

    Fibriani, Azzania; Wisaksana, Rudi; Alisjahbana, Bachti; Indrati, Agnes; Schutten, Martin; van Crevel, Reinout; van der Ven, Andre; Boucher, Charles A B

    2014-04-01

    Indonesia currently faces both an increasing HIV incidence and a high hepatitis B virus (HBV) burden. The objective of our study is to examine the prevalence, risk factors, and genotypic distribution of HBV infection among HIV infected patients in West Java, Indonesia. A cross sectional study was conducted among a cohort of HIV infected patients in 2008. Demographic and disease related variables were compared between HBV negative and positive patients. Logistic regression was applied to determine risk factors for HBV co-infection. HBV and HIV genotyping was performed in co-infected patients. Of 636 HIV-infected patients, the rate of HBV co-infection was 7%. The proportion of males was higher in HBV/HIV co-infected patients than in HIV mono-infected patients (93% vs. 72%, P=0.001). A history of injecting drug use (IDU), but not tattooing, was associated with HBV co-infection [P=0.035 OR 2.41 (95% CI 1.06-5.47)]. In the HIV and HBV treatment naive patients, CD4 cells counts Java. However, an increased prevalence was observed in men with a history of IDU, underlining the need for routine HBV screening and monitoring. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Annual research review: Rare genotypes and childhood psychopathology--uncovering diverse developmental mechanisms of ADHD risk.

    Science.gov (United States)

    Scerif, Gaia; Baker, Kate

    2015-03-01

    Through the increased availability and sophistication of genetic testing, it is now possible to identify causal diagnoses in a growing proportion of children with neurodevelopmental disorders. In addition to developmental delay and intellectual disability, many genetic disorders are associated with high risks of psychopathology, which curtail the wellbeing of affected individuals and their families. Beyond the identification of significant clinical needs, understanding the diverse pathways from rare genetic mutations to cognitive dysfunction and emotional-behavioural disturbance has theoretical and practical utility. We overview (based on a strategic search of the literature) the state-of-the-art on causal mechanisms leading to one of the most common childhood behavioural diagnoses - attention deficit hyperactivity disorder (ADHD) - in the context of specific genetic disorders. We focus on new insights emerging from the mapping of causal pathways from identified genetic differences to neuronal biology, brain abnormalities, cognitive processing differences and ultimately behavioural symptoms of ADHD. First, ADHD research in the context of rare genotypes highlights the complexity of multilevel mechanisms contributing to psychopathology risk. Second, comparisons between genetic disorders associated with similar psychopathology risks can elucidate convergent or distinct mechanisms at each level of analysis, which may inform therapeutic interventions and prognosis. Third, genetic disorders provide an unparalleled opportunity to observe dynamic developmental interactions between neurocognitive risk and behavioural symptoms. Fourth, variation in expression of psychopathology risk within each genetic disorder points to putative moderating and protective factors within the genome and the environment. A common imperative emerging within psychopathology research is the need to investigate mechanistically how developmental trajectories converge or diverge between and within

  8. VKORC1 and CYP2C9 genotypes are predictors of warfarin-related outcomes in children.

    Science.gov (United States)

    Shaw, Kaitlyn; Amstutz, Ursula; Hildebrand, Claudette; Rassekh, S Rod; Hosking, Martin; Neville, Kathleen; Leeder, J Steven; Hayden, Michael R; Ross, Colin J; Carleton, Bruce C

    2014-06-01

    Despite substantial evidence supporting a pharmacogenetic approach to warfarin therapy in adults, evidence on the importance of genetics in warfarin therapy in children is limited, particularly for clinical outcomes. We assessed the contribution of CYP2C9/VKORC1/CYP4F2 genotypes and variation in other genes involved in vitamin K and coagulation pathways to warfarin dose and related clinical outcomes in children. Clinical and genetic data for 93 children (age ≤ 18 years) who received warfarin therapy were obtained. DNA was genotyped for 93 selected single nucleotide polymorphisms using a custom assay. With a median age of 4.8 years, our cohort included more young children than most previous studies. Overall, 76.3% of dose variability was explained by weight, indication, VKORC1-1639G/A and CYP2C9 *2/*3, with genotypes accounting for 21.1% of variability. There was a strong correlation (R(2) = 0.68; P 4; P = 0.024) during the initiation of therapy. CYP2C9*3 carriers were also at increased risk of major bleeding while receiving warfarin (adjusted OR = 11.28). An additional variant in CYP2C9 (rs7089580) was significantly associated with warfarin dose (P = 0.020) in a multivariate clinical and genetic model. This study confirms the importance of VKORC1/CYP2C9 genotypes for warfarin dosing in a young pediatric cohort and demonstrates an impact of genetic factors on clinical outcomes in children. Furthermore, we identified an additional variant in CYP2C9 of potential relevance for warfarin dosing in children. © 2014 Wiley Periodicals, Inc.

  9. Interleukin-10 (IL-10) promoter genotypes are associated with lung cancer risk in Taiwan males and smokers.

    Science.gov (United States)

    Hsia, Te-Chun; Chang, Wen-Shin; Liang, Shinn-Jye; Chen, Wei-Chun; Tu, Chih-Yen; Chen, Hung-Jen; Yang, Mei-Due; Tsai, Chia-Wen; Hsu, Chin-Mu; Tsai, Chang-Hai; Bau, Da-Tian

    2014-12-01

    Interleukin-10 (IL-10) is an immunosuppressive cytokine involved in carcinogenesis via immune escape. The present study aimed at evaluating the contribution of IL-10 promoter A-1082G (rs1800896), T-819C (rs3021097), A-592C (rs1800872) genetic polymorphisms to the risk of lung cancer in Taiwan. Associations of three IL-10 polymorphic genotypes with lung cancer risk were investigated among 358 lung cancer patients and 716 age- and gender-matched healthy controls. In addition, the genetic-lifestyle interaction was also examined. The results showed that the percentages of TT, TC and CC for IL-10 T-819C genotypes were differentially represented as 59.2%, 35.8% and 5.0% in the lung-cancer patient group and 52.0%, 37.0% and 11.0% in the non-cancer control group, respectively (p for trend=0.0025). The CC genotype carriers were of lower risk for lung cancer (OR=0.4, 95% CI=0.23-0.69, p=0.0005). Further stratification of the population by gender and smoking behavior showed that the IL-10 T-819C genotype conducted a protective effect on lung cancer susceptibility, which was obvious among males and smokers (p=0.0003 and 0.0004, respectively). The CC and TC genotypes of IL-10 T-819C compared to the TT genotype may have a protective effect on lung cancer risk in Taiwan, particularly among males and smokers.

  10. Apolipoprotein E and Alzheimer disease: Genotype-specific risks by age and sex

    Energy Technology Data Exchange (ETDEWEB)

    Bickeboeller, H. [INSERM, Paris (France)]|[IMSE, Munich (Germany); Babron, M.C.; Clerget-Darpoux, F. [INSERM, Paris (France)] [and others

    1997-02-01

    The distribution of apolipoprotein E (APOE) genotypes as a function of age and sex has been examined in a French population of 417 Alzheimer disease (AD) patients and 1,030 control subjects. When compared to the APOE {epsilon}3 allele, an increased risk associated with the APOE {epsilon}4 allele (odds ratio [OR] [{epsilon}4] = 2.7 with 95% confidence interval [CI] = 2.0-3.6; P < .001) and a protective effect of the APOE {epsilon}2 allele (OR[{epsilon}2] = 0.5 with 95% CI = 0.3-0.98; P = .012) were retrieved. An effect of the {epsilon}4 allele dosage on susceptibility was confirmed (OR[{epsilon}4/{epsilon}4] vs. the {epsilon}3/{epsilon}3 genotype = 11.2 [95% CI = 4.0-31.6]; OR[{epsilon}3/{epsilon}4] vs. the {epsilon}3/{epsilon}3 genotype = 2.2 [95% Cl = 1.5-3.5]). The frequency of the {epsilon}4 allele was lower in male cases than in female cases, but, since a similar difference was found in controls, this does not lead to a difference in OR between sex. ORs for the {epsilon}4 allele versus the {epsilon}3 allele, OR({epsilon}4), were not equal in all age classes: OR({epsilon}4) in the extreme groups with onset at < 60 years or > 79 years were significantly lower than those from the age groups 60-79 years. In {epsilon}3/{epsilon}4 individuals, sex-specific lifetime risk estimates by age 85 years (i.e., sex-specific penetrances by age 85 years) were 0.14 (95% CI 0.04-0.30) for men and 0.17 (95% CI 0.09-0.28) for women. 53 refs., 1 fig., 3 tabs.

  11. Predicting PTSD using the New York Risk Score with genotype data: potential clinical and research opportunities

    Directory of Open Access Journals (Sweden)

    Boscarino JA

    2013-04-01

    Full Text Available Joseph A Boscarino,1,2 H Lester Kirchner,3,4 Stuart N Hoffman,5 Porat M Erlich1,4 1Center for Health Research, Geisinger Clinic, Danville, 2Department of Psychiatry, Temple University School of Medicine, Philadelphia, 3Division of Medicine, Geisinger Clinic, Danville, 4Department of Medicine, Temple University School of Medicine, Philadelphia, 5Department of Neurology, Geisinger Clinic, Danville, PA, USA Background: We previously developed a post-traumatic stress disorder (PTSD screening instrument, ie, the New York PTSD Risk Score (NYPRS, that was effective in predicting PTSD. In the present study, we assessed a version of this risk score that also included genetic information. Methods: Utilizing diagnostic testing methods, we hierarchically examined different prediction variables identified in previous NYPRS research, including genetic risk-allele information, to assess lifetime and current PTSD status among a population of trauma-exposed adults. Results: We found that, in predicting lifetime PTSD, the area under the receiver operating characteristic curve (AUC for the Primary Care PTSD Screen alone was 0.865. When we added psychosocial predictors from the original NYPRS to the model, including depression, sleep disturbance, and a measure of health care access, the AUC increased to 0.902, which was a significant improvement (P = 0.0021. When genetic information was added in the form of a count of PTSD risk alleles located within FKBP, COMT, CHRNA5, and CRHR1 genetic loci (coded 0–6, the AUC increased to 0.920, which was also a significant improvement (P = 0.0178. The results for current PTSD were similar. In the final model for current PTSD with the psychosocial risk factors included, genotype resulted in a prediction weight of 17 for each risk allele present, indicating that a person with six risk alleles or more would receive a PTSD risk score of 17 × 6 = 102, the highest risk score for any of the predictors studied. Conclusion: Genetic

  12. Common bean genotypes for agronomic and market-related traits in VCU trials

    Directory of Open Access Journals (Sweden)

    Alisson Fernando Chiorato

    2015-02-01

    Full Text Available Value for Cultivation and Use (VCU trials are undertaken when evaluating improved common bean (Phaseolus vulgaris L. lines, and knowledge of agronomic and market-related traits and disease reaction is instrumental in making cultivar recommendations. This study evaluates the yield, cooking time, grain color and reaction to anthracnose (Colletotrichum lindemuthianum, Fusarium wilt (Fusarium oxysporum f. sp. phaseoli and Curtobacterium wilt (Curtobacterium flaccumfaciens pv. flaccumfaciens of 25 common bean genotypes derived from the main common bean breeding programs in Brazil. Seventeen VCU trials were carried out in the rainy season, dry season and winter season from 2009 to 2011 in the state of São Paulo. Analyses of grain color and cooking time were initiated 60 days after harvest, and disease reaction analyses were performed in the laboratory under controlled conditions. In terms of yield, no genotype superior to the controls was observed for any of the seasons under consideration. Grains from the dry season exhibited better color, while the rainy season led to the shortest cooking times. The following genotypes BRS Esteio, BRS Esplendor and IAC Imperador were resistant to anthracnose, Fusarium wilt and Curtobacterium wilt and, in general, genotypes with lighter-colored grains were more susceptible to anthracnose and Fusarium wilt.

  13. Alcohol drinking habits, alcohol dehydrogenase genotypes and risk of acute coronary syndrome

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Hansen, J.L.; Gronbaek, M.

    2010-01-01

    Aims: The risk of myocardial infarction is lower among light-to-moderate drinkers compared with abstainers. Results from some previous studies, but not all, suggest that this association is modified by variations in genes coding for alcohol dehydrogenase (ADH). We aimed to test this hypothesis......). Results: Higher alcohol intake (measured as amount or drinking frequency) was associated with lower risk of acute coronary syndrome; however, there was no evidence that these finding were modified by ADH1B or ADH1C genotypes. Conclusions: The importance of functional variation in alcohol dehydrogenase......, including alcohol as both the amount of alcohol and the frequency of drinking. Methods: we conducted a nested case-cohort study within the Danish Diet, Cancer and Health study, including 1,645 men (770 incident cases of acute coronary syndrome from 1993-1997 through 2004 and 875 randomly selected controls...

  14. Glutathione S-transferase M1 and T1 genotypes and endometriosis risk: a case-controlled study

    Institute of Scientific and Technical Information of China (English)

    林俊; 张信美; 钱羽力; 叶英辉; 石一复; 徐开红; 徐键云

    2003-01-01

    Objective To investigate the correlation between glutathione S-transferase (GST) M1 and T1 genotypes and endometriosis risk (EM). Methods Polymerase chain reaction (PCR) technique was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA isolated from the blood samples of 68 Han Chinese women with endometriosis and 28 without endometriosis. Results The frequencies of GSTM1 and GSTT1 null genotypes in women with endometriosis were 0.721 (49/68) and 0.779 (53/68), respectively, and in women without endometriosis were 0.429 (12/28) and 0.321 (9/28), respectively. There was a significant difference with regard to the frequencies of GSTM1 and GSTT1 null genotypes between the women with and without endometriosis (P0.05). Conclusion GSTM1 and GSTT1 null genotypes may be risk factors for the development of endometriosis.

  15. DD genotype of ACE gene in boys: may it be a risk factor for minimal change nephrotic syndrome?

    Science.gov (United States)

    Alasehirli, Belgin; Balat, Ayşe; Büyükçelik, Mithat

    2012-01-01

    It has been shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects the circulating and cellular levels of ACE and may be a risk factor in several renal diseases. We analyzed the association of ACE gene I/D polymorphism with the clinical presentation of minimal change nephrotic syndrome (MCNS) in a Turkish child population. This study consisted of 97 children with MCNS and 144 healthy controls. Genotyping of ACE gene was performed using polymerase chain reaction (PCR). The distributions of ACE genotypes were II in 13%, ID in 49%, and DD in 38% in patient group, and 9%, 49%, and 42% in control group, respectively. The frequency of the D allele was 63% and that of the I allele was 37% in patients. There were no relevant differences in the allele frequencies and genotypes of ACE I/D polymorphism between patients and controls. However, DD genotype was higher in boys in children with MCNS (78.4%. vs. 50.0%, p = 0.004). The frequencies of DD genotype and D allele in boys were 7.25 and 2.56 times higher than II genotype and I allele in the patient group, respectively. We suggest that DD genotype in boys may be one of the risk factors for MCNS.

  16. Maternal serotonin transporter genotype affects risk for ASD with exposure to prenatal stress.

    Science.gov (United States)

    Hecht, Patrick M; Hudson, Melissa; Connors, Susan L; Tilley, Michael R; Liu, Xudong; Beversdorf, David Q

    2016-11-01

    Stress exposure during gestation is implicated in several neuropsychiatric conditions, including autism spectrum disorder (ASD). Previous research showed that prenatal stress increases risk for ASD with peak exposure during the end of the second and the beginning of the third trimester. However, exposures to prenatal stress do not always result in ASD, suggesting that other factors may interact with environmental stressors to increase ASD risk. The present study examined a maternal genetic variation in the promoter region of the serotonin transporter gene (5-HTTLPR) affecting stress tolerance and its interaction with the effect of environmental stressors on risk for ASD. Two independent cohorts of mothers of ASD children recruited by the University of Missouri and Queen's University were surveyed regarding the prenatal environment and genotyping on 5-HTTLPR was performed to explore this relationship. In both samples, mothers of children with ASD carrying the stress susceptible short allele variant of 5-HTTLPR experienced a greater number of stressors and greater stress severity when compared to mothers carrying the long allele variant. The temporal peak of stressors during gestation in these mothers was consistent with previous findings. Additionally, increased exposure to prenatal stress was not reported in the pregnancies of typically developing siblings from the same mothers, regardless of maternal genotype, suggesting against the possibility that the short allele might increase the recall of stress during pregnancy. The present study provides further evidence of a specific maternal polymorphism that may affect the risk for ASD with exposure to prenatal stress. Autism Res 2016, 9: 1151-1160. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  17. The Interaction of Obesity Related Genotypes, Phenotypes, and Economics: An Experimental Economics Approach with Mice

    OpenAIRE

    Davis, George C.; Jacob, Jacy; Deborah J Good

    2011-01-01

    Food intake is greatly influenced by economic factors. Consequently, neuroeconomics has been identified as a new and important area for understanding the interaction between genotypes and phenotypes related to food intake. A foundational element of economics is choice between alternatives. Changing food choices are a central element in the explanation of the increasing obesity rates in human populations. The purpose of this research is to incorporate the key element of choice into the investi...

  18. CFTR genotype-related body water and electrolyte balance during a marathon.

    Science.gov (United States)

    Del Coso, J; Lara, B; Salinero, J J; Areces, F; Ruiz-Vicente, D; Gallo-Salazar, C; Abián-Vicén, J; Cacabelos, R

    2016-09-01

    The aim of this investigation was to determine the influence of CFTR genotype on body water and electrolyte balance during a marathon. Fifty-one experienced runners completed a marathon race. Before and after the race, body mass and a sample of venous blood were obtained. During the race, sweat samples were collected using sweat patches, and fluid and electrolyte intake were obtained using self-reported questionnaires. Thirty-eight participants (74.5% of the total) were 7T/7T homozygotes, 11 (21.6%) were 7T/9T heterozygotes, and one participant presented the rare genotype 5T/7T. Another participant with 9T/9T presented the mutation p.L206W. Participants with 7T/7T showed higher sweat sodium concentrations (42.2 ± 21.6 mmol/L) than 7T/9T (29.0 ± 24.7 mmol/L; P = 0.04). The runner with the 5T/7T genotype (10.2 mmol/L) and the participant with the p.L206W mutation (20.5 mmol/L) exhibited low-range sweat sodium concentrations. However, post-race serum sodium concentration was similar in 7T/7T and 7T/9T (142.1 ± 1.3 and 142.4 ± 1.6 mmol/L, respectively; P = 0.27) and did not show abnormalities in participants with the 5T/7T genotype (140.0 mmol/L) and the p.L206W mutation (143.0 mmol/L). Runners with the CFTR-7T/7T genotype exhibited increased sweat sodium concentrations during a marathon. However, this phenotype was not related with increased likelihood of suffering body water and electrolyte imbalances during real competitions.

  19. Common genetic variability in ESR1 and EGF in relation to endometrial cancer risk and survival

    OpenAIRE

    Einarsdóttir, K; Darabi, H; Czene, K.; Li, Y; Low, Y.L.; Y. Q. Li; Bonnard, C.; Wedrén, S.; Liu, E. T.; Hall, P; Liu, J; Humphreys, K.

    2009-01-01

    We investigated common genetic variation in the entire ESR1 and EGF genes in relation to endometrial cancer risk, myometrial invasion and endometrial cancer survival. We genotyped a dense set of single-nucleotide polymorphisms (SNPs) in both genes and selected haplotype tagging SNPs (tagSNPs). The tagSNPs were genotyped in 713 Swedish endometrial cancer cases and 1567 population controls and the results incorporated into logistic regression and Cox proportional hazards models. We found five a...

  20. Non-travel related Hepatitis E virus genotype 3 infections in the Netherlands; A case series 2004 – 2006

    Directory of Open Access Journals (Sweden)

    Bosman Arnold

    2008-05-01

    Full Text Available Abstract Background Human hepatitis E virus (HEV infections are considered an emerging disease in industrialized countries. In the Netherlands, Hepatitis E virus (HEV infections have been associated with travel to high-endemic countries. Non-travel related HEV of genotype 3 has been diagnosed occasionally since 2000. A high homology of HEV from humans and pigs suggests zoonotic transmission but direct molecular and epidemiological links have yet to be established. We conducted a descriptive case series to generate hypotheses about possible risk factors for non-travel related HEV infections and to map the genetic diversity of HEV. Methods A case was defined as a person with HEV infection laboratory confirmed (positive HEV RT-PCR and/or HEV IgM after 1 January 2004, without travel to a high-endemic country three months prior to onset of illness. For virus identification 148 bp of ORF2 was sequenced and compared with HEV from humans and pigs. We interviewed cases face to face using a structured questionnaire and collected information on clinical and medical history, food preferences, animal and water contact. Results We interviewed 19 cases; 17 were male, median age 50 years (25–84 y, 12 lived in the North-East of the Netherlands and 11 had preexisting disease. Most common symptoms were dark urine (n = 16 and icterus (n = 15. Sixteen ate pork ≥ once/week and six owned dogs. Two cases had received blood transfusions in the incubation period. Seventeen cases were viremic (genotype 3 HEV, two had identical HEV sequences but no identified relation. For one case, HEV with identical sequence was identified from serum and surface water nearby his home. Conclusion The results show that the modes of transmission of genotype-3 HEV infections in the Netherlands remains to be resolved and that host susceptibility may play an important role in development of disease.

  1. GSTM1 null genotype and gastric cancer risk in the Chinese population: an updated meta-analysis and review

    Directory of Open Access Journals (Sweden)

    Zhang XL

    2015-04-01

    Full Text Available Xi-Liang Zhang, Yong-Hui Cui Department of Gastroenterology, The First People’s Hospital of Shangqiu City, Shangqiu, Henan, People’s Republic of China Abstract: Although a number of studies have been conducted on the association between the GSTM1 null genotype and gastric cancer in People’s Republic of China, this association remains elusive and controversial. To clarify the effects of the GSTM1 null genotype on the risk of gastric cancer, an updated meta-analysis was performed in the Chinese population. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI, and Chinese Biology Medicine (CBM up to November 5, 2014. A total of 25 studies including 3,491 cases and 5,921 controls were included in this meta-analysis. Overall, a significant association (odds ratio [OR] =1.47, 95% CI: 1.28–1.69 was found between the null GSTM1 and gastric cancer risk when all studies in Chinese population were pooled into the meta-analysis. In subgroup analyses stratified by quality score, geographic area, and source of controls, the same results were observed. Additionally, a significant association was found both in smokers and non-smokers. This meta-analysis showed that the null GSTM1 may be a potential biomarker for gastric cancer risk in Chinese, and further studies with gene–gene and gene–environment interactions are required for definite conclusions. Keywords: meta-analysis, GSTM1, polymorphism, gastric cancer

  2. GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.

    Science.gov (United States)

    Fernández-Cadenas, Israel; Mendióroz, Maite; Giralt, Dolors; Nafria, Cristina; Garcia, Elena; Carrera, Caty; Gallego-Fabrega, Cristina; Domingues-Montanari, Sophie; Delgado, Pilar; Ribó, Marc; Castellanos, Mar; Martínez, Sergi; Freijo, Marimar; Jiménez-Conde, Jordi; Rubiera, Marta; Alvarez-Sabín, José; Molina, Carlos A; Font, Maria Angels; Grau Olivares, Marta; Palomeras, Ernest; Perez de la Ossa, Natalia; Martinez-Zabaleta, Maite; Masjuan, Jaime; Moniche, Francisco; Canovas, David; Piñana, Carlos; Purroy, Francisco; Cocho, Dolores; Navas, Inma; Tejero, Carlos; Aymerich, Nuria; Cullell, Natalia; Muiño, Elena; Serena, Joaquín; Rubio, Francisco; Davalos, Antoni; Roquer, Jaume; Arenillas, Juan Francisco; Martí-Fábregas, Joan; Keene, Keith; Chen, Wei-Min; Worrall, Bradford; Sale, Michele; Arboix, Adrià; Krupinski, Jerzy; Montaner, Joan

    2017-05-01

    Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS. We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method. The analyses revealed that rs1800801 in the MGP gene (hazard ratio, 1.33; P=9×10(-)(03)), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (P=3.2×10(-)(09)) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared with previous Stroke Prognosis Instrument-II score (P=0.03). The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population. © 2017 American Heart Association, Inc.

  3. Relation between genotype, phenotype and therapeutic drug concentrations of nortriptyline or venlafaxine users in old age psychiatry

    NARCIS (Netherlands)

    Berm, E.J.J.; Kok, R.M.; Hak, E.; Wilffert, B.

    2015-01-01

    Background The relationship between phenotype and genotype of the polymorphic cytochrome P450 2D6 enzyme (CYP2D6) has been intensively studied, however few studies are conducted among older persons. In a study among 900 relatively young venlafaxine users (mean age 45 years), 83% were genotyped as an

  4. Null genotypes of GSTM1 and GSTT1 contribute to increased risk of diabetes mellitus: a meta-analysis.

    Science.gov (United States)

    Zhang, Jingwen; Liu, Hu; Yan, Hongyi; Huang, Guoliang; Wang, Bin

    2013-04-15

    Diabetes mellitus (DM) is a common disease which results from various causes including genetic and environmental factors. Glutathione S-Transferase M1 (GSTM1) and Glutathione S-Transferase T1 (GSTT1) genes are polymorphic in human and the null genotypes lead to the absence of enzyme function. Many studies assessed the associations between GSTM1/GSTT1 null genotypes and DM risk but reported conflicting results. In order to get a more precise estimate of the associations of GSTM1/GSTT1 null genotypes with DM risk, we performed this meta-analysis. Published literature from PubMed, Embase and China Biology Medicine (CBM) databases was searched for eligible studies. Pooled odds ratios (OR) and corresponding 95% confidence intervals (95%CI) were calculated using a fixed- or random-effects model. 11 publications (a total of 2577 cases and 4572 controls) were finally included into this meta-analysis. Meta-analyses indicated that null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1-GSTT1 were all associated with increased risk of DM (GSTM1: OR random-effects=1.60, 95%CI 1.10-2.34, POR=0.014; GSTT1: OR random-effects=1.47, 95%CI 1.12-1.92, POR=0.005; GSTM1-GSTT1: OR fixed-effects=1.83, 95%CI 1.30-2.59, POR=0.001). Subgroup by ethnicity suggested significant associations between null genotypes of GSTM1 and GSTT1 and DM risk among Asians (GSTM1: OR random-effects=1.77, 95%CI 1.24-2.53, POR=0.002; GSTT1: OR random-effects=1.58, 95%CI 1.09-2.27, POR=0.015). This meta-analysis suggests null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1-GSTT1 are all associated with increased risk of DM, and null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1-GSTT1 are potential biomarkers of DM.

  5. Relative risk regression analysis of epidemiologic data.

    Science.gov (United States)

    Prentice, R L

    1985-11-01

    Relative risk regression methods are described. These methods provide a unified approach to a range of data analysis problems in environmental risk assessment and in the study of disease risk factors more generally. Relative risk regression methods are most readily viewed as an outgrowth of Cox's regression and life model. They can also be viewed as a regression generalization of more classical epidemiologic procedures, such as that due to Mantel and Haenszel. In the context of an epidemiologic cohort study, relative risk regression methods extend conventional survival data methods and binary response (e.g., logistic) regression models by taking explicit account of the time to disease occurrence while allowing arbitrary baseline disease rates, general censorship, and time-varying risk factors. This latter feature is particularly relevant to many environmental risk assessment problems wherein one wishes to relate disease rates at a particular point in time to aspects of a preceding risk factor history. Relative risk regression methods also adapt readily to time-matched case-control studies and to certain less standard designs. The uses of relative risk regression methods are illustrated and the state of development of these procedures is discussed. It is argued that asymptotic partial likelihood estimation techniques are now well developed in the important special case in which the disease rates of interest have interpretations as counting process intensity functions. Estimation of relative risks processes corresponding to disease rates falling outside this class has, however, received limited attention. The general area of relative risk regression model criticism has, as yet, not been thoroughly studied, though a number of statistical groups are studying such features as tests of fit, residuals, diagnostics and graphical procedures. Most such studies have been restricted to exponential form relative risks as have simulation studies of relative risk estimation

  6. Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Coric, Vesna M; Simic, Tatjana P; Pekmezovic, Tatjana D; Basta-Jovanovic, Gordana M; Savic Radojevic, Ana R; Radojevic-Skodric, Sanja M; Matic, Marija G; Dragicevic, Dejan P; Radic, Tanja M; Bogdanovic, Ljiljana M; Dzamic, Zoran M; Pljesa-Ercegovac, Marija S

    2016-01-01

    The aim of this study was to evaluate specific glutathione S-transferase (GST) gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC), independently or simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and pnull, GSTT1-active, GSTA1-low activity and GSTP1-variant genotype, exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype combination (p = 0.04). Significant association between GST genotype and cRCC risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1-variant/GSTA1 low-activity genotype combination was present in 94% of smokers with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02). Furthermore, cRCC smokers with GSTM1-null genotype had significantly higher concentration of BPDE-DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05). GSTM1, GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC, with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1-null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be considered as "risk-carrying genotype combination" in cRCC.

  7. Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review

    Directory of Open Access Journals (Sweden)

    Nebel Almut

    2010-01-01

    Full Text Available Abstract Apolipoprotein E is a polymorphic and multifunctional protein with numerous roles in lipoprotein metabolism. The three common isoforms apoE2, apoE3 and apoE4 show isoform-specific functional properties including different susceptibilities to diseases. ApoE4 is an accepted risk factor for Alzheimer's disease and cardiovascular disorders. Recently, associations between apoE4 and infectious diseases have been demonstrated. This review summarises how apoE4 may be involved in the infection incidence and associated pathologies of specific infectious diseases, namely hepatitis C, human immunodeficiency virus disease and herpes simplex. ApoE4 seems to be protective against chronic hepatitis C virus infection and retards fibrosis progression. In contrast apoE4 enhances the fusion rate of human immunodeficiency virus with target cell membranes, resulting in accelerated cell entry and faster disease progression. Its association with human immunodeficiency virus-associated dementia remains controversial. Regarding herpes simplex virus infection, apoE4 intensifies virus latency and is associated with increased oxidative damage of the central nervous system, and there is some evidence that herpes simplex virus infection in combination with the apoE4 genotype may be associated with an increased risk of Alzheimer's disease. In addition to reviewing available data from human trials, evidence derived from a variety of cell culture and animal models are considered in this review in order to provide mechanistic insights into observed association between apoE4 genotype and viral disease infection and pathology.

  8. Indoor tanning and the MC1R genotype: risk prediction for basal cell carcinoma risk in young people.

    Science.gov (United States)

    Molinaro, Annette M; Ferrucci, Leah M; Cartmel, Brenda; Loftfield, Erikka; Leffell, David J; Bale, Allen E; Mayne, Susan T

    2015-06-01

    Basal cell carcinoma (BCC) incidence is increasing, particularly in young people, and can be associated with significant morbidity and treatment costs. To identify young individuals at risk of BCC, we assessed existing melanoma or overall skin cancer risk prediction models and built a novel risk prediction model, with a focus on indoor tanning and the melanocortin 1 receptor gene, MC1R. We evaluated logistic regression models among 759 non-Hispanic whites from a case-control study of patients seen between 2006 and 2010 in New Haven, Connecticut. In our data, the adjusted area under the receiver operating characteristic curve (AUC) for a model by Han et al. (Int J Cancer. 2006;119(8):1976-1984) with 7 MC1R variants was 0.72 (95% confidence interval (CI): 0.66, 0.78), while that by Smith et al. (J Clin Oncol. 2012;30(15 suppl):8574) with MC1R and indoor tanning had an AUC of 0.69 (95% CI: 0.63, 0.75). Our base model had greater predictive ability than existing models and was significantly improved when we added ever-indoor tanning, burns from indoor tanning, and MC1R (AUC = 0.77, 95% CI: 0.74, 0.81). Our early-onset BCC risk prediction model incorporating MC1R and indoor tanning extends the work of other skin cancer risk prediction models, emphasizes the value of both genotype and indoor tanning in skin cancer risk prediction in young people, and should be validated with an independent cohort. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Smoking, apolipoprotein E genotypes, and mortality (the Ludwigshafen RIsk and Cardiovascular Health study).

    Science.gov (United States)

    Grammer, Tanja B; Hoffmann, Michael M; Scharnagl, Hubert; Kleber, Marcus E; Silbernagel, Günther; Pilz, Stefan; Tomaschitz, Andreas; Lerchbaum, Elisabeth; Siekmeier, Rüdiger; März, Winfried

    2013-05-01

    The genetic polymorphism of apolipoprotein E (APOE) has been suggested to modify the effect of smoking on the development of coronary artery disease (CAD) in apparently healthy persons. The interaction of these factors in persons undergoing coronary angiography is not known. We analysed the association between the APOE-genotype, smoking, angiographic CAD, and mortality in 3263 participants of the LUdwigshafen RIsk and Cardiovascular Health study. APOE-genotypes were associated with CAD [ε22 or ε23: odds ratio (OR) 0.56, 95% confidence interval (CI) 0.43-0.71; ε24 or ε34 or ε44: OR 1.10, 95% CI 0.89-1.37 compared with ε33] and moderately with cardiovascular mortality [ε22 or ε23: hazard ratio (HR) 0.71, 95% CI 0.51-0.99; ε33: HR 0.92, 95% CI 0.75-1.14 compared with ε24 or ε34 or ε44]. HRs for total mortality were 1.39 (95% CI 0.39-0.1.67), 2.29 (95% CI 1.85-2.83), 2.07 (95% CI 1.64-2.62), and 2.95 (95% CI 2.10-4.17) in ex-smokers, current smokers, current smokers without, or current smokers with one ε4 allele, respectively, compared with never-smokers. Carrying ε4 increased mortality in current, but not in ex-smokers (HR 1.66, 95% CI 1.04-2.64 for interaction). These findings applied to cardiovascular mortality, were robust against adjustment for cardiovascular risk factors, and consistent across subgroups. No interaction of smoking and ε4 was seen regarding non-cardiovascular mortality. Smokers with ε4 had reduced average low-density lipoprotein (LDL) diameters, elevated oxidized LDL, and lipoprotein-associated phospholipase A2. In persons undergoing coronary angiography, there is a significant interaction between APOE-genotype and smoking. The presence of the ε4 allele in current smokers increases cardiovascular and all-cause mortality.

  10. A novel zoonotic genotype related to Echinococcus granulosus sensu stricto from southern Ethiopia.

    Science.gov (United States)

    Wassermann, Marion; Woldeyes, Daniel; Gerbi, Banchwosen Mechal; Ebi, Dennis; Zeyhle, Eberhard; Mackenstedt, Ute; Petros, Beyene; Tilahun, Getachew; Kern, Peter; Romig, Thomas

    2016-09-01

    Complete mitochondrial and two nuclear gene sequences of a novel genotype (GOmo) related to Echinococcus granulosus sensu stricto are described from a metacestode isolate retrieved from a human patient in southwestern Ethiopia. Phylogenetically, the genotype is positioned within the E. granulosus sensu stricto/Echinococcus felidis cluster, but cannot easily be allocated to either species. Based on different mitochondrial DNA markers, it is closest to the haplotype cluster that currently defines the species E. granulosus sensu stricto (which includes variants showing the widely cited G1, G2 and G3 sequences), but is clearly not part of this cluster. Pairwise distances between GOmo and E. granulosus sensu stricto are in the range of those between the most distant members of the Echinococcus canadensis complex (G6-10) that were recently proposed as separate species. At this stage, we prefer to list GOmo informally as a genotype rather than giving it any taxonomic rank because our knowledge rests on a single isolate from a dead-end host (human), and its lifecycle is unknown. According to data on molecularly characterised Echinococcus isolates from this region, GOmo has never been found in the usual livestock species that carry cystic echinococcosis and the possibility of a wildlife source of this newly recognised zoonotic agent cannot be excluded. The discovery of GOmo adds complexity to the already diverse array of cystic echinococcosis agents in sub-Saharan Africa and challenges hypotheses on the biogeographical origin of the E. granulosus sensu stricto clade.

  11. Genotypes and phenotypes in cystic fibrosis and cystic fibrosis transmembrane regulator-related disorders.

    Science.gov (United States)

    Bombieri, Cristina; Seia, Manuela; Castellani, Carlo

    2015-04-01

    Cystic fibrosis (CF) is characterized by remarkable variability in severity, rate of disease progression, and organ involvement. In spite of the considerable amount of data collected on the relationship between genotype and phenotype in CF, this is still a challenging matter of debate. Barriers to the interpretation of this connection are the large number of mutations in the CF transmembrane regulator (CFTR) gene, the difficulties in attributing several of them to a specific mode of dysfunction, and a limited number of the almost 2,000 mutations so far detected, which have been clinically annotated. In addition to that, the heterogeneity of clinical manifestations in individuals with the same CFTR genotypes indicates that disease severity is modulated by other genes and by environmental factors, of which the most relevant is possibly treatment in its aspects of appropriateness, early start in life, and adherence. The phenotype variability extends to conditions, named CFTR-related disorders, which are connected with CFTR dysfunction, but do not satisfy diagnostic criteria for CF. The current level of knowledge does not allow use of the CFTR genotype to predict individual outcome and cannot be used as an indicator of CF prognosis. This might change with the development of treatments targeting specific mutations and possibly capable of changing the natural history of the disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Campylobacter jejuni capsular genotypes are related to Guillain-Barré syndrome.

    Science.gov (United States)

    Heikema, A P; Islam, Z; Horst-Kreft, D; Huizinga, R; Jacobs, B C; Wagenaar, J A; Poly, F; Guerry, P; van Belkum, A; Parker, C T; Endtz, H P

    2015-09-01

    In about one in a thousand cases, a Campylobacter jejuni infection results in the severe polyneuropathy Guillain-Barré syndrome (GBS). It is established that sialylated lipo-oligosaccharides (LOS) of C. jejuni are a crucial virulence factor in GBS development. Frequent detection of C. jejuni with sialylated LOS in stools derived from patients with uncomplicated enteritis implies that additional bacterial factors should be involved. To assess whether the polysaccharide capsule is a marker for GBS, the capsular genotypes of two geographically distinct GBS-associated C. jejuni strain collections and an uncomplicated enteritis control collection were determined. Capsular genotyping of C. jejuni strains from the Netherlands revealed that three capsular genotypes, HS1/44c, HS2 and HS4c, were dominant in GBS-associated strains and capsular types HS1/44c and HS4c were significantly associated with GBS (p 0.05 and p 0.01, respectively) when compared with uncomplicated enteritis. In a GBS-associated strain collection from Bangladesh, capsular types HS23/36c, HS19 and HS41 were most prevalent and the capsular types HS19 and HS41 were associated with GBS (p 0.008 and p 0.02, respectively). Next, specific combinations of the LOS class and capsular genotypes were identified that were related to the occurrence of GBS. Multilocus sequence typing revealed restricted genetic diversity for strain populations with the capsular types HS2, HS19 and HS41. We conclude that capsular types HS1/44c, HS2, HS4c, HS19, HS23/36c and HS41 are markers for GBS. Besides a crucial role for sialylated LOS of C. jejuni in GBS pathogenesis, the identified capsules may contribute to GBS susceptibility.

  13. Pharmacokinetics of lansoprazole in Chinese healthy subjects in relation to CYP2C19 genotypes

    Institute of Scientific and Technical Information of China (English)

    Yu-rong HU; Hai-ling QIAO; Quan-cheng KAN

    2004-01-01

    AIM: To study the kinetic characteristics of lansoprazole in healthy Chinese subjects in relation to CYP2C19 genotype status for the individualized dose regimen of lansoprazole. METHODS: Nine homozygous extensive metabolizers (homo EMs) and 9 poor metabolizers (PMs) were recruited for the study from a total of 70 healthy Chinese volunteers, whose CYP2C19 genotype status was determined by the PCR-RFLP techniques. After a single oral dose of 30 mg lansoprazole capsule, plasma concentrations of lansoprazole were determined with HPLC method. RESULTS: In Chinese subjects, the allele frequencies of the CYP2C19ml and CYP2C19m2 mutation were 0.35 and 0.07, respectively. The concentration-time curves in the two groups were best fitted to a one-compartment model. In the homo EMs and the PMs groups, the main kinetic parameters were as follows: Tmax(2.44±0.85)and (2.33±0.94) h, Cmax (1.10±0.34) and (1.73±0.56) mg/L, Cl/F (16.55±6.38) and (3.58± 1) L/h, T1/2ke (1.96±0.51)Cmax values existed between the two groups (P<0.01). CONCLUSION: CYP2C19 genotype is the major factor to influence the interindividual kinetic variability of lansoprazole. Individualized dose regimen of lansoprazole, based on identification of genotype, can be of great benefit for the reasonable use of this drug.

  14. The GSTM1 null genotype increased risk of gastric cancer: a meta-analysis based on 46 studies.

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    Full Text Available BACKGROUND: Glutathione S-transferases M1 (GSTM1 is an important phase II metabolizing enzyme. The null genotype of GSTM1 causes total loss of GSTM1 enzyme activity and numerous studies have investigated the association between GSTM1 null genotype and gastric cancer risk. METHODS: This meta-analysis was designed to investigate the relationship between GSTM1 null genotype and susceptibility to gastric cancer and assess the influence of Helicobacter pylori infection, smoking, Lauren's classification, and other factors. Odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the association strength. RESULTS: A total of 46 eligible studies were indentified and analyzed in this meta-analysis, including 8138 cases of gastric cancer and 13867 controls. Pooled results showed that the GSTM1 null genotype was associated with a significantly increased risk of gastric cancer (OR=1.217, 95% CI: 1.113-1.331, P(heterogeneity<0.001. Sub-group analysis suggested that the significant association was only observed in Asians (OR=1.273, 95%: 1.137-1.426, P(heterogeneity= 0.002, but not in Caucasians. The increased risk was found among H. pylori positive population (OR=1.928, 95% CI: 1.028-3.615, P(heterogeneity=0.065, while no association was found among H. pylori negative population (OR=0.969, 95% CI: 0.618-1.521, P(heterogeneity=0.168. For smoking status, the GSTM1 null genotype increased risk of gastric cancer in both ever-smokers and non-smokers. Source of control, sample size, location of tumor and Lauren's classification did not modify the association. CONCLUSIONS: In this meta-analysis based on 46 epidemiological studies, we show that the GSTM1 null genotype is associated with an increased risk of gastric cancer among Asians but not among Caucasians. H. pylori infection but not smoking status could modify the association.

  15. Risk Aversion Relates to Cognitive Ability

    DEFF Research Database (Denmark)

    Andersson, Ola; Holm, Håkan J.; Tyran, Jean-Robert Karl

    2016-01-01

    Recent experimental studies suggest that risk aversion is negatively related to cognitive ability. In this paper we report evidence that this relation might be spurious. We recruit a large subject pool drawn from the general Danish population for our experiment. By presenting subjects with choice...... tasks that vary the bias induced by random choices, we are able to generate both negative and positive correlations between risk aversion and cognitive ability. Structural estimation allowing for heterogeneity of noise yields no significant relation between risk aversion and cognitive ability. Our...... results suggest that cognitive ability is related to random decision making, rather than to risk preferences....

  16. Risk aversion relates to cognitive ability

    DEFF Research Database (Denmark)

    Andersson, Ola; Holm, Håkan J.; Tyran, Jean-Robert Karl

    Recent experimental studies suggest that risk aversion is negatively related to cognitive ability. In this paper we report evidence that this relation might be spurious. We recruit a large subject pool drawn from the general Danish population for our experiment. By presenting subjects with choice...... tasks that vary the bias induced by random choices, we are able to generate both negative and positive correlations between risk aversion and cognitive ability. Structural estimation allowing for heterogeneity of noise yields no significant relation between risk aversion and cognitive ability. Our...... results suggest that cognitive ability is related to random decision making rather than to risk preferences....

  17. HPV Genotyping from the high risk mRNA Aptima assay- a direct approach using DNA from Aptima sample tubes.

    Science.gov (United States)

    Lillsunde Larsson, G; Kaliff, M; Bergengren, L; Karlsson, M G; Helenius, G

    2016-09-01

    The underlying cause of cervical cancer is an infection with the human papilloma virus (HPV) and HPV testing can be used for cervical cancer screening. The Aptima HPV assay from Hologic is an mRNA HPV test used to identify clinically relevant infections but the method does not discriminate between the different high risk genotypes. The aim of the current study was to evaluate if analyzed Aptima sample transfer tubes could be used as a source for HPV genotyping, using sample DNA. Study samples (n=108); were HPV-tested with mRNA Aptima assay and in parallel DNA was extracted and genotyped with Anyplex II HPV28. Analyzed mRNA Aptima tubes were thereafter used as source for a second DNA extraction and genotyping. Using mRNA Aptima result as reference, 90% of the samples (35/39) were high risk positive with the Anyplex II HPV28. Cohen's kappa 0.78 (95% CI: 0.66-0.90), sensitivity 0.90 (95% CI: 0.76-0.97) and specificity 0.90 (95% CI: 0.80-0.96). Two discordant samples carried low-risk genotypes (HPV 82 and HPV 44) and two were negative. DNA-genotyping results, in parallel to and after mRNA testing, were compared and differed significantly (McNemar test: P=0.021) possibly due to sample extraction volume difference. Cohen's kappa 0.81 (95% CI: 0.70-0.92), sensitivity 0.85 (95% CI: 0.74-0.93) and specificity 0.98 (95% CI: 0.88-1.00). In conclusion, analyzed mRNA Aptima sample tubes could be used as a source for DNA HPV genotyping. The sample volume used for extraction needs to be further explored.

  18. Elevated Lipoprotein(a) Levels, LPA Risk Genotypes, and Increased Risk of Heart Failure in the General Population

    DEFF Research Database (Denmark)

    Kamstrup, Pia R; Nordestgaard, Børge G

    2016-01-01

    OBJECTIVES: This study sough to test whether elevated lipoprotein(a) levels and corresponding LPA risk genotypes (low number of kringle IV type 2 repeats, rs3798220 and rs10455872, minor allele carriers) are associated with an increased risk of heart failure (HF). BACKGROUND: Elevated lipoprotein......(a) levels represent a genetically determined risk factor for myocardial infarction (MI) and aortic valve stenosis (AVS). It is presently unknown whether elevated lipoprotein(a) levels also cause heart failure (HF). METHODS: We combined 2 general population studies, the Copenhagen City Heart Study (n = 10...... mediation analyses. RESULTS: Elevated lipoprotein(a) levels were associated with multivariable adjusted hazard ratios for HF of 1.10 (95% CI: 0.97 to 1.25) for the 34th to 66th percentiles (8 to 19 mg/dl), 1.24 (95% CI: 1.08 to 1.42) for the 67th to 90th percentiles (20 to 67 mg/dl), 1.57 (95% CI: 1.32 to 1...

  19. Cost-utility analysis of genotype-guided antiplatelet therapy in patients with moderate-to-high risk acute coronary syndrome and planned percutaneous coronary intervention

    Directory of Open Access Journals (Sweden)

    Patel V

    2014-09-01

    Full Text Available Background: Prasugrel is recommended over clopidogrel in poor/intermediate CYP2C19 metabolizers with acute coronary syndrome (ACS and planned percutaneous coronary intervention (PCI, reducing the risk of ischemic events. CYP2C19 genetic testing can guide antiplatelet therapy in ACS patients. Objective: The purpose of this study was to evaluate the cost-utility of genotype-guided treatment, compared with prasugrel or generic clopidogrel treatment without genotyping, from the US healthcare provider’s perspective. Methods: A decision model was developed to project lifetime economic and humanistic burden associated with clinical outcomes (myocardial infarction [MI], stroke and major bleeding for the three strategies in patients with ACS. Probabilities, costs and age-adjusted quality of life were identified through systematic literature review. Incremental cost-utility ratios (ICURs were calculated for the treatment strategies, with quality-adjusted life years (QALYs as the primary effectiveness outcome. Relative risk of developing myocardial infarction and stroke between patients with and without variant CYP2C19 when receiving clopidogrel were estimated to be 1.34 and 3.66, respectively. One-way and probabilistic sensitivity analyses were performed. Results: Clopidogrel cost USD19,147 and provided 10.03 QALYs versus prasugrel (USD21,425, 10.04 QALYs and genotype-guided therapy (USD19,231, 10.05 QALYs. The ICUR of genotype-guided therapy compared with clopidogrel was USD4,200. Genotype-guided therapy provided more QALYs at lower costs compared with prasugrel. Results were sensitive to the cost of clopidogrel and relative risk of myocardial infarction and stroke between CYP2C19 variant vs. non-variant. Net monetary benefit curves showed that genotype-guided therapy had at least 70% likelihood of being the most cost-effective alternative at a willingness-to-pay of USD100,000/QALY. In comparison with clopidogrel, prasugrel therapy was more cost

  20. Phenotype-Genotype Analysis of Chinese Patients with Early-Onset LMNA-Related Muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Dandan Tan

    Full Text Available This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA-related muscular dystrophy (MD. The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293 cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD. Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype-genotype analysis determines that some mutations are well correlated with LMNA-related MD.

  1. Tumor Genotype Determines Phenotype and Disease-related Outcomes in Thyroid Cancer

    Science.gov (United States)

    Yip, Linwah; Nikiforova, Marina N.; Yoo, Jenny Y.; McCoy, Kelly L.; Stang, Michael T.; Armstrong, Michaele J.; Nicholson, Kristina J.; Ohori, N. Paul; Coyne, Christopher; Hodak, Steven P.; Ferris, Robert L.; LeBeau, Shane O.; Nikiforov, Yuri E.; Carty, Sally E.

    2017-01-01

    Objectives To correlate thyroid cancer genotype with histology and outcomes. Background The prognostic significance of molecular signature in thyroid cancer (TC) is undefined but can potentially change surgical management. Methods We reviewed a consecutive series of 1510 patients who had initial thyroidectomy for TC with routine testing for BRAF, RAS, RET/PTC, and PAX8/PPARG alterations. Histologic metastatic or recurrent TC was tracked for 6 or more months after oncologic thyroidectomy. Results Papillary thyroid cancer (PTC) was diagnosed in 97% of patients and poorly differentiated/anaplastic TC in 1.1%. Genetic alterations were detected in 1039 (70%); the most common mutations were BRAFV600E (644/1039, 62%), and RAS isoforms (323/1039, 31%). BRAFV600E-positive PTC was often conventional or tall cell variant (58%), with frequent extrathyroidal extension (51%) and lymph node metastasis (46%). Conversely, RAS-positive PTC was commonly follicular variant (87%), with infrequent extrathyroidal extension (4.6%) and lymph node metastasis (5.6%). BRAFV600E and RET/PTC-positive PTCs were histologically similar. Analogously, RAS and PAX8/PPARG-positive PTCs were histologically similar. Compared with RAS or PAX8/PPARG-positive TCs, BRAFV600E or RET/PTC-positive TCs were more often associated with stage III/IV disease (40% vs 15%, P cancers, with higher risks of both distant metastasis and early recurrence. Preoperative genotype provides valuable prognostic data to appropriately inform surgery. PMID:26258321

  2. GSTT1 null genotype contributes to lung cancer risk in asian populations: a meta-analysis of 23 studies.

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    Xin Yang

    Full Text Available BACKGROUND: Genetic variation in glutathione S-transferases (GSTs may contribute to lung cancer risk. Many studies have investigated the correlation between the Glutathione S-transferase T1 (GSTT1 null genotype and lung cancer risk in Asian population but yielded inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 23 studies including 4065 cases and 5390 controls. We assessed the strength of the association of GSTT1 with lung cancer risk and performed sub-group analyses by source of controls, smoking status, histological types, and sample size. A statistically significant correlation between GSTT1 null genotype and lung cancer in Asian population was observed (OR = 1.28, 95% CI = 1.10, 1.49; Pheterogeneity<0.001 and I(2 = 62.0%. Sub-group analysis revealed there was a statistically increased lung cancer risk in ever-smokers who carried the GSTT1 null genotype (OR = 1.94, 95% CI = 1.27, 2.96; P heterogeneity = 0.02 and I(2 = 58.1%. It was also indicated that GSTT1 null genotype could increase lung cancer risk among population-based studies (OR = 1.25, 95% CI = 1.04, 1.50; Pheterogeneity = 0.003 and I(2 = 56.8%. The positive association was also found in studies of sample size (≤500 participants (OR = 1.34, 95% CI = 1.10, 1.62; Pheterogeneity<0.001 and I(2 = 65.4%. CONCLUSIONS: These meta-analysis results suggest that GSTT1 null genotype is associated with a significantly increased risk of lung cancer in Asian population.

  3. Analytical Validation of a Personalized Medicine APOL1 Genotyping Assay for Nondiabetic Chronic Kidney Disease Risk Assessment

    Science.gov (United States)

    Zhang, Jinglan; Fedick, Anastasia; Wasserman, Stephanie; Zhao, Geping; Edelmann, Lisa; Bottinger, Erwin P.; Kornreich, Ruth; Scott, Stuart A.

    2017-01-01

    The incidence of chronic kidney disease (CKD) varies by ancestry, with African Americans (AA) having a threefold to fourfold higher rate than whites. Notably, two APOL1 alleles, termed G1 [c.(1072A>G; 1200T>G)] and G2 (c.1212_1217del6), are strongly associated with higher rates of nondiabetic CKD and an increased risk for hypertensive end-stage renal disease. This has prompted the opportunity to implement APOL1 testing to identify at-risk patients and modify other risk factors to reduce the progression of CKD to end-stage renal disease. We developed an APOL1 genotyping assay using multiplex allele-specific primer extension, and validated using 58 positive and negative controls. Genotyping results were completely concordant with Sanger sequencing, and both triplicate interrun and intrarun genotyping results were completely concordant. Multiethnic APOL1 allele frequencies were also determined by genotyping 7059 AA, Hispanic, and Asian individuals from the New York City metropolitan area. The AA, Hispanic, and Asian APOL1 G1 and G2 allele frequencies were 0.22 and 0.13, 0.037 and 0.025, and 0.013 and 0.004, respectively. Notably, approximately 14% of the AA population carried two risk alleles and are at increased risk for CKD, compared with <1% of the Hispanic and Asian populations. This novel APOL1 genotyping assay is robust and highly accurate, and represents one of the first personalized medicine clinical genetic tests for disease risk prediction. PMID:26773863

  4. Effects of FTO genotype on weight loss and metabolic risk factors in response to calorie restriction among Japanese women.

    Science.gov (United States)

    Matsuo, Tomoaki; Nakata, Yoshio; Murotake, Yukako; Hotta, Kikuko; Tanaka, Kiyoji

    2012-05-01

    Effects of gene variants in the fat-mass and obesity-associated (FTO) gene (primarily rs9939609) on weight loss induced by lifestyle intervention are controversial. The aim of this study was to investigate whether FTO gene variations are associated with weight-reduction and changes in metabolic risk factors in response to a 14-week calorie restriction. In total, 204 Japanese women (aged 24-66 years; BMI ≥ 25 kg/m(2)) enrolled as subjects and attended dietary lectures instructing them on how to consume a nutritionally balanced diet of 1,200 kcal/day. Fat mass, both at baseline (P = 0.100) and after the intervention (P = 0.020), was higher in subjects with the AA genotype (n = 15; 7.3%) than in those with TT (n = 114; 55.9%) and TA (n = 75; 36.8%) genotypes. The change in fat-mass tended to be smaller in subjects with the AA genotype than in those with other genotypes (P = 0.065). However, the subjects with the risk allele could still decrease their body weight and improve metabolic risk factors significantly. Our data suggest that the impact of FTO rs9939609 in Japanese women may not be great enough to change body weight or metabolic risk factors in response to calorie restriction. Environmental and behavioral factors may overcome the effects of genes on weight reduction.

  5. Apolipoprotein E4 genotype does not increase risk of HIV-associated neurocognitive disorders.

    Science.gov (United States)

    Morgan, E E; Woods, S P; Letendre, S L; Franklin, D R; Bloss, C; Goate, A; Heaton, R K; Collier, A C; Marra, C M; Gelman, B B; McArthur, J C; Morgello, S; Simpson, D M; McCutchan, J A; Ellis, R J; Abramson, I; Gamst, A; Fennema-Notestine, C; Smith, D M; Grant, I; Vaida, F; Clifford, D B

    2013-04-01

    This is a cross-sectional, observational study to evaluate the hypothesis that HIV-seropositive (HIV+) apolipoprotein E4 (APOE4) carriers are at increased risk for HIV-associated neurocognitive disorders (HAND) compared to APOE4 noncarriers with HIV in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Group sample. APOE genotype was determined in 466 CHARTER participants with varying disease stages and histories of antiretroviral treatment who did not have severe psychiatric or medical comorbid conditions that preclude diagnosis of HAND. HAND diagnoses were based on results of comprehensive neurobehavioral evaluation and use of current neuroAIDS diagnostic criteria. HAND status consists of two levels: neuropsychologically normal status (i.e., no HAND) and any HAND diagnosis (i.e., asymptomatic neurocognitive impairment, minor neurocognitive disorder, HIV-associated dementia). Logistic regression analyses revealed no association between APOE4 carrier status and HAND, and there were no interactions between APOE4 carrier status and ethnicity, age, substance use disorders, duration of infection, or nadir CD4. Results did not differ when analysis was restricted to symptomatic HAND, and no APOE4 gene dose-dependent relationship to HAND emerged. APOE4 status was not associated with concurrent HAND in this large, well-characterized sample. This does not preclude emergence of an association between APOE4 status and HAND as this population ages. Prospective, longitudinal studies are needed to examine APOE4 as a risk factor for neurocognitive decline, incident HAND at older ages, and potential associations with cerebrospinal fluid amyloid.

  6. Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis.

    Science.gov (United States)

    Chen, Li-Shiun; Baker, Timothy; Hung, Rayjean J; Horton, Amy; Culverhouse, Robert; Hartz, Sarah; Saccone, Nancy; Cheng, Iona; Deng, Bo; Han, Younghun; Hansen, Helen M; Horsman, Janet; Kim, Claire; Rosenberger, Albert; Aben, Katja K; Andrew, Angeline S; Chang, Shen-Chih; Saum, Kai-Uwe; Dienemann, Hendrik; Hatsukami, Dorothy K; Johnson, Eric O; Pande, Mala; Wrensch, Margaret R; McLaughlin, John; Skaug, Vidar; van der Heijden, Erik H; Wampfler, Jason; Wenzlaff, Angela; Woll, Penella; Zienolddiny, Shanbeh; Bickeböller, Heike; Brenner, Hermann; Duell, Eric J; Haugen, Aage; Brüske, Irene; Kiemeney, Lambertus A; Lazarus, Philip; Le Marchand, Loic; Liu, Geoffrey; Mayordomo, Jose; Risch, Angela; Schwartz, Ann G; Teare, M Dawn; Wu, Xifeng; Wiencke, John K; Yang, Ping; Zhang, Zuo-Feng; Spitz, Margaret R; Amos, Christopher I; Bierut, Laura J

    2016-09-01

    Recent meta-analyses show that individuals with high risk variants in CHRNA5 on chromosome 15q25 are likely to develop lung cancer earlier than those with low-risk genotypes. The same high-risk genetic variants also predict nicotine dependence and delayed smoking cessation. It is unclear whether smoking cessation confers the same benefits in terms of lung cancer risk reduction for those who possess CHRNA5 risk variants versus those who do not. Meta-analyses examined the association between smoking cessation and lung cancer risk in 15 studies of individuals with European ancestry who possessed varying rs16969968 genotypes (N=12,690 ever smokers, including 6988 cases of lung cancer and 5702 controls) in the International Lung Cancer Consortium. Smoking cessation (former vs. current smokers) was associated with a lower likelihood of lung cancer (OR=0.48, 95%CI=0.30-0.75, p=0.0015). Among lung cancer patients, smoking cessation was associated with a 7-year delay in median age of lung cancer diagnosis (HR=0.68, 95%CI=0.61-0.77, p=4.9∗10(-10)). The CHRNA5 rs16969968 risk genotype (AA) was associated with increased risk and earlier diagnosis for lung cancer, but the beneficial effects of smoking cessation were very similar in those with and without the risk genotype. We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7years for those who develop it. These results: 1) underscore the potential value of smoking cessation for all smokers, 2) suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3) have potential value for framing preventive interventions for those who smoke. Copyright © 2016

  7. Distribution of high-risk human papillomavirus genotypes among HIV-negative women with and without cervical intraepithelial neoplasia in South Africa.

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    Alicia C McDonald

    Full Text Available OBJECTIVE: Large studies describing the profile of high-risk Human papillomavirus (hrHPV genotypes among women in sub-Saharan Africa are lacking. Here we describe the prevalence and distribution of hrHPV genotypes among HIV-negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN. METHODS: We report data on 8,050 HIV-negative women, aged 17-65 years, recruited into three sequential studies undertaken in Cape Town, South Africa. Women had no history of previous cervical cancer screening. Cervical samples were tested for hrHPV DNA using the Hybrid Capture 2 (HC2 assay and all positive samples were genotyped using a PCR-based assay (Line Blot. Women underwent colposcopy and biopsy/endocervical curettage to determine CIN status. The prevalence and distribution of specific hrHPV genotypes were examined by age and CIN status. RESULTS: Overall, 20.7% (95% CI, 19.9-21.6% of women were hrHPV-positive by HC2, with women with CIN having the highest rates of positivity. Prevalence decreased with increasing age among women without CIN; but, a bimodal age curve was observed among women with CIN. HPV 16 and 35 were the most common hrHPV genotypes in all age and CIN groups. HPV 45 became more frequent among older women with CIN grade 2 or 3 (CIN2,3. Younger women (17-29 years had more multiple hrHPV genotypes overall and in each cervical disease group than older women (40-65 years. CONCLUSION: HPV 16, 35, and 45 were the leading contributors to CIN 2,3. The current HPV vaccines could significantly reduce HPV-related cervical disease; however, next generation vaccines that include HPV 35 and 45 would further reduce cervical disease in this population.

  8. Risk Estimates and Risk Factors Related to Psychiatric Inpatient Suicide

    DEFF Research Database (Denmark)

    Madsen, Trine; Erlangsen, Annette; Nordentoft, Merete

    2017-01-01

    trends, and socio-demographic and clinical risk factors of suicide in psychiatric inpatients. Psychiatric inpatients have a very high risk of suicide relative to the background population, but it remains challenging for clinicians to identify those patients that are most likely to die from suicide during...... admission. Most studies are based on low power, thus compromising quality and generalisability. The few studies with sufficient statistical power mainly identified non-modifiable risk predictors such as male gender, diagnosis, or recent deliberate self-harm. Also, the predictive value of these predictors......People with mental illness have an increased risk of suicide. The aim of this paper is to provide an overview of suicide risk estimates among psychiatric inpatients based on the body of evidence found in scientific peer-reviewed literature; primarily focusing on the relative risks, rates, time...

  9. Cytochrome CYP2E1 phenotyping and genotyping in the evaluation of health risks from exposure to polluted environments.

    Science.gov (United States)

    Lucas, D; Ferrara, R; Gonzales, E; Albores, A; Manno, M; Berthou, F

    2001-10-15

    Humans are exposed to over 70,000 man-made chemicals including drugs, food additives, herbicides, pesticides, and industrial agents. It is well established that environmental chemicals are the cause of numerous human diseases including cancer. In most cases, chemical carcinogens require metabolic activation, which is mainly achieved by P450s enzymes. CYP2E1 is of clinical relevance because it is inducible by ethanol, and it metabolizes many common organic solvents such as benzene, alcohols and halogenated solvents. Therefore, alteration in the level of CYP2E1 might influence the health effects of the environmental pollutants. This hypothesis needs to be validated by epidemiological studies and the objective of the "Biomed-2" project was to develop new tests to assess the individual metabolic capacity of workers exposed to volatile organic compounds in order to predict their occupational risk. In vivo chlorzoxazone 6-hydroxylation was validated as a non-invasive and selective test for the determination of liver CYP2E1 activity. Preliminary data in workers exposed to organic solvents indicated that chlorzoxazone metabolism may be a biomarker of occupational exposure to organic solvents. Other approaches, such as use of salicylate as catalytic probe or measurement of catalytic activity in lymphocytes, were not conclusive. Attempts to use CYP2E1 genotyping for estimating human risks from chemical exposure did not bring convincing data as genetic polymorphism of CYP2E1 could not be clearly related to its catalytic activity.

  10. Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes — A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Li-Shiun Chen

    2016-09-01

    Conclusion: We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7 years for those who develop it. These results: 1 underscore the potential value of smoking cessation for all smokers, 2 suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3 have potential value for framing preventive interventions for those who smoke.

  11. Occurrence, genotyping, shiga toxin genes and associated risk factors of E. coli isolated from dairy farms, handlers and milk consumers.

    Science.gov (United States)

    Awadallah, M A; Ahmed, H A; Merwad, A M; Selim, M A

    2016-11-01

    The objectives of the current study were to determine the occurrence and genotypes of E. coli in dairy farms, workers and milk consumers and to evaluate risk factors associated with contamination of milk in dairy farms. Molecular characterization of shiga toxin associated genes and enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) finger printing of E. coli from different sources were also studied. Paired milk samples and rectal swabs from 125 dairy cows, rectal swabs from 82 calves and hand swabs from 45 dairy workers from five dairy farms were collected. In addition, 100 stool samples from 70 diarrheic and 30 healthy humans were collected and examined for the presence of E. coli. E. coli was isolated from milk (22.4%), dairy cattle feces (33.6%), calf feces (35.4%), dairy worker hand swabs (11.1%) and stools of milk consumers (2%, from diarrheic patients only). Only stx1 was identified in seven of 12 E. coli O125 isolated from different sources. High genetic diversity was determined (Simpson's index of diversity, D = 1) and E. coli O125 isolates were classified into 12 distinct profiles, E1-E12. The dendrogram analysis showed that two main clusters were generated. Mastitis in dairy cows was considered a risk factor associated with contamination of the produced milk with E. coli. The isolation of E. coli from rectal swabs of dairy cows and calves poses a zoonotic risk through consumption of unpasteurized contaminated dairy milk. Educational awareness should be developed to address risks related to consumption of raw milk. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Survival of Bemisia tabaci and activity of plant defense-related enzymes in genotypes of Capsicum annuum L.

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    Luis Latournerie-Moreno

    2015-03-01

    Full Text Available The whitefly Bemisia tabaci (Gennadius, 1889 is a major plant pest of horticultural crops from the families Solanaceae, Fabaceae and Cucurbitaceae in Neotropical areas. The exploration of host plant resistance and their biochemical mechanisms offers an excellent alternative to better understand factors affecting the interaction between phytophagous insect and host plant. We evaluated the survival of B. tabaci in landrace genotypes of Capsicum annuum L., and the activity of plant defense-related enzymes (chitinase, polyphenoloxidase, and peroxidase. The landrace genotypes Amaxito, Tabaquero, and Simojovel showed resistance to B. tabaci, as we observed more than 50% nymphal mortality, while in the commercial susceptible genotype Jalapeño mortality of B. tabaci nymphs was not higher than 20%. The activities of plant defense-related enzymes were significantly different among pepper genotypes (P < 0.05. Basal activities of chitinase, polyphenoloxidase and peroxidase were significantly lower or equal in landrace genotypes than that of the commercial genotype Jalapeño. The activity of plant enzymes was differential among pepper genotypes (P < 0.05. For example, the activity of chitinase enzyme generally was higher in non-infested plants with B. tabaci than those infested. Instead polyphenoloxidase ('Amaxito' and 'Simojovel' and peroxidase enzymes activities ('Tabaquero' increased in infested plants (P < 0.05. We conclude that basal activities of plant defense-related enzymes could be act through other mechanism plant induction, since plant defense-related enzymes showed a different induction response to B. tabaci. We underlined the role of polyphenoloxidase as plant defense in the pepper genotype Simojovel related to B. tabaci.

  13. ABCA7 Genotypes Confer Alzheimer's Disease Risk by Modulating Amyloid-β Pathology.

    Science.gov (United States)

    Zhao, Qing-Fei; Wan, Yu; Wang, Hui-Fu; Sun, Fu-Rong; Hao, Xiao-Ke; Tan, Meng-Shan; Tan, Chen-Chen; Zhang, Dao-Qiang; Tan, Lan; Yu, Jin-Tai

    2016-03-21

    ABCA7 gene has been identified as a strong genetic locus for Alzheimer's disease (AD) susceptibility in genome wide association studies (GWAS). However, the possible roles of ABCA7 variants in AD pathology were not specifically assessed. Using tagger methods, we extracted 15 targeted ABCA7 loci to investigate their associations with cerebrospinal fluid (CSF) and neuroimaging markers in Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Finally, although we did not detect any significant associations of previously published GWAS SNPs (rs3764650 and rs78117248) with all the CSF (Aβ1 - 42, T-tau, and P-tau) and neuroimaging markers, three other variants (rs3752242, rs3752240, and rs4147912) at ABCA7 loci were detected to show significant associations with amyloid deposition on AV-45 PET in brain. Moreover, haplotype and subgroup analysis confirmed these significant findings. Furthermore, there were no remarkable correlations between ABCA7 variants and neuronal degeneration biomarkers (elevated CSF tau, brain structure atrophy, and hypometabolism on imaging) in this study. Thus, our study suggested that ABCA7 genotypes contribute to the AD risk through involvement in amyloid-β deposition on in vivo imaging, but not in tau pathology, brain atrophy, or decreased glucose metabolism.

  14. Comparing triage algorithms using HPV DNA genotyping, HPV E7 mRNA detection and cytology in high-risk HPV DNA-positive women.

    Science.gov (United States)

    Luttmer, Roosmarijn; Berkhof, Johannes; Dijkstra, Maaike G; van Kemenade, Folkert J; Snijders, Peter J F; Heideman, Daniëlle A M; Meijer, Chris J L M

    2015-06-01

    High-risk human papillomavirus (hrHPV) DNA positive women require triage testing to identify those with high-grade cervical intraepithelial neoplasia or cancer (≥CIN2). Comparing three triage algorithms (1) E7 mRNA testing following HPV16/18/31/33/45/52/58 genotyping (E7 mRNA test), (2) HPV16/18 DNA genotyping and (3) cytology, for ≥CIN2 detection in hrHPV DNA-positive women. hrHPV DNA-positive women aged 18-63 years visiting gynecology outpatient clinics were included in a prospective observational cohort study. From these women a cervical scrape and colposcopy-directed biopsies were obtained. Cervical scrapes were evaluated by cytology, HPV DNA genotyping by bead-based multiplex genotyping of GP5+6+-PCR-products, and presence of HPV16/18/31/33/45/52/58 E7 mRNA using nucleic acid sequence-based amplification (NASBA) in DNA positive women for respective HPV types. Sensitivities and specificities for ≥CIN2 were compared between E7 mRNA test and HPV16/18 DNA genotyping in the total group (n=348), and E7 mRNA test and cytology in a subgroup of women referred for non-cervix-related gynecological complaints (n=133). Sensitivity for ≥CIN2 of the E7 mRNA test was slightly higher than that of HPV16/18 DNA genotyping (66.9% versus 60.9%; ratio 1.10, 95% CI: 1.0002-1.21), at similar specificity (54.8% versus 52.3%; ratio 1.05, 95% CI: 0.93-1.18). Neither sensitivity nor specificity of the E7 mRNA test differed significantly from that of cytology (sensitivity: 68.8% versus 75.0%; ratio 0.92, 95% CI: 0.72-1.17; specificity: 59.4% versus 65.3%; ratio 0.91, 95% CI: 0.75-1.10). For detection of ≥CIN2 in hrHPV DNA-positive women, an algorithm including E7 mRNA testing following HPV16/18/31/33/45/52/58 DNA genotyping performs similar to HPV16/18 DNA genotyping or cytology. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Apolipoprotein E3/E3 genotype decreases the risk of pituitary dysfunction after traumatic brain injury due to various causes: preliminary data.

    Science.gov (United States)

    Tanriverdi, Fatih; Taheri, Serpil; Ulutabanca, Halil; Caglayan, Ahmet Okay; Ozkul, Yusuf; Dundar, Munis; Selcuklu, Ahmet; Unluhizarci, Kursad; Casanueva, Felipe F; Kelestimur, Fahrettin

    2008-09-01

    Traumatic brain injury (TBI) is a devastating public health problem which may result in hypopituitarism. However, the mechanisms and the risk factors responsible for hypothalamo-pituitary dysfunction due to TBI are still unclear. Although APO E is one of the most abundant protein in hypothalamo-pituitary region, there is no study investigating the relation between APO E polymorphism and TBI-induced hypopituitarism. This study was undertaken to determine whether APO E genotypes modulate the pituitary dysfunction risk after TBI due to various causes, including traffic accident, boxing, and kickboxing. Ninety-three patients with TBI (mean age, 30.61 +/- 1.25 years) and 27 healthy controls (mean age, 29.03 +/- 1.70 years) were included in the study. Pituitary functions were evaluated, and APO E genotypes (E2/E2; E3/E3; E4/E4; E2/E3; E2/E4; E3/E4) were screened. Twenty-four of 93 subjects (25.8%) had pituitary dysfunction after TBI. The ratio of pituitary dysfunction was significantly lower in subjects with APO E3/E3 (17.7%) than the subjects without APO E3/E3 genotype (41.9%; p = 0.01), and the corresponding odds ratio was 0.29 (95% confidence interval [CI], 0.11-0.78). In conclusion, this study provides strong evidence for the first time that APO E polymorphism is associated with the development of TBI-induced pituitary dysfunction. Present data demonstrated that APO E3/E3 genotype decreases the risk of hypopituitarism after TBI. The demonstration of the association between the APO E polymorphism and TBI may provide a new point of view in this field and promote further studies.

  16. The methylenetetrahydrofolate reductase C677T genotype and the risk of obesity in three large population-based cohorts.

    Science.gov (United States)

    Lewis, Sarah J; Lawlor, Debbie A; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne; Ebrahim, Shah; Zacho, Jeppe; Ness, Andy; Leary, Sam; Smith, George Davey

    2008-07-01

    Epidemiological studies have shown that low folate levels are associated with a high body mass index (BMI). These findings have potentially important health implications and warrant further investigation to determine whether a causal relationship exists and the direction of this relationship. The methylenetetrahydrofolate reductase (MTHFR) C677T TT genotype is associated with reduced folate availability and may be a surrogate for measuring folate levels. We sought to determine whether MTHFR C677T genotype was associated with obesity. We carried out our study on four populations from three longitudinal studies based in the UK and Denmark in which DNA for genotyping was obtained along with measures of obesity. Our subjects were taken from the British Women's Heart and Health Study (BWHHS), the Avon Longitudinal Study of Parents and Children (two populations: mothers and children) and the Copenhagen City Heart Study. We performed analyses separately by population, and then carried out a meta-analysis, combining similar populations. Initial findings in the BWHHS suggested that the TT genotype may be associated with an increased risk of obesity BMI > or =30, however, no association was found with BMI or central adiposity in this cohort. This genotype was not associated with obesity in our other cohorts. Our results suggest that the initial positive finding with obesity in the BWHHS was a chance finding. Our findings do not support a causal effect of low folate on obesity.

  17. Identification of Resistance Gene to PVY and Its Relation to Marketable Tuber Yield of PVY Resistant Potato Genotypes

    Directory of Open Access Journals (Sweden)

    Hassan Hassanabadi

    2016-10-01

    Full Text Available In this study, the Rysto gene, originaly found in wild potato (Solanum stoloniferum, confers extreme resistance against PVY. It was identified in 21 potato clones and varieties and they were evaluated for some agronomic traits. For this purpose five trials were conducted. In first trial 320 potato genotypes were planted on the farm and 55 symptomless clone and cultivars were selected. In second trial, 55 genotypes along with sensitive control genotype (Desireh were planted in 20 cm pots in the greenhouse at 15-20 °C with three replications. After five weeks, upper leaves were infected artificially with sap from tobacco fresh leaves checked for infection with PVYNTN and additional infections were repeated after 48 hours. Symptoms were recorded and all plants were tested by enzyme-linked immunosorbent assay (ELISA about 4 weeks after inoculation. Plants that showed visual symptoms or/and gave at least a positive ELISA result were considered as susceptible and symptomless response with negative ELISA results were considered as resistant. In third trial, 23 genotypes were planted in the greenhouse and the PVY infected young tobacco shoots were grafted to symptomless genotypes with negative ELISA results with three replications and were selected as resistance genotypes. In fourth trial, all the PVY resistant genotypes were checked by molecular marker (STM0003 for detection of Rysto gene. Finally four potato varieties (Jelly, Sante, White Lady and Savalan cultivars and 19 advanced clones were regarded as carriers of Rysto gene. In the fifth experiment genotypes were evaluated for marketable tuber yield of varieties and clones resistant to virus PVY in field conditions and 397009-8 clone was selected as high-yielding and tolerant genotype to PVY virus. Also, This clone did also have appropriate quality traits like oval-round tuber shape, uniform tubers, short stolon length, light yellow flesh color, yellow skin color, good tuber dry matter percent

  18. Ancestry of the Timorese: age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world

    Science.gov (United States)

    Morrison, Margaux A.; Magalhaes, Tiago R.; Ramke, Jacqueline; Smith, Silvia E.; Ennis, Sean; Simpson, Claire L.; Portas, Laura; Murgia, Federico; Ahn, Jeeyun; Dardenne, Caitlin; Mayne, Katie; Robinson, Rosann; Morgan, Denise J.; Brian, Garry; Lee, Lucy; Woo, Se J.; Zacharaki, Fani; Tsironi, Evangelia E.; Miller, Joan W.; Kim, Ivana K.; Park, Kyu H.; Bailey-Wilson, Joan E.; Farrer, Lindsay A.; Stambolian, Dwight; DeAngelis, Margaret M.

    2015-01-01

    We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age > 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus. PMID:26217379

  19. Fetal and maternal MTHFR C677T genotype, maternal folate intake and the risk of nonsyndromic oral clefts.

    Science.gov (United States)

    Chevrier, Cécile; Perret, Claire; Bahuau, Michel; Zhu, Huiping; Nelva, Agnès; Herman, Christine; Francannet, Christine; Robert-Gnansia, Elisabeth; Finnell, Richard H; Cordier, Sylvaine

    2007-02-01

    The association between maternal folate intake and risk of nonsyndromic oral clefts has been studied among many populations with conflicting results. The methylenetetrahydrofolate reductase gene (MTHFR) plays a major role in folate metabolism, and several polymorphisms, including C677T, are common in European populations. Data from a French study (1998-2001) let us investigate the roles of maternal dietary folate intake and the MTHFR polymorphism and their interaction on the risk of cleft lip with/without cleft palate (CL/P) and cleft palate only (CP). We used both case-control (164 CL/P, 76 CP, 236 controls; 148, 59, 168 of whom, respectively, had an available genotype) and case-parent (143 CL/P and 56 CP families) study designs and distinguished the role of the child's genotype and maternally mediated effects on risks. This study observed a beneficial effect of mothers' dietary folate intake on their offspring's risk (odds ratio (OR)(P, OR([230-314 microg/day]) = 0.56, 95% confidence interval = 0.3-0.9, OR(>314 microg/day) = 0.64, 0.4-1.1; for CP, OR([230-314 microg/day]) = 1.15, 0.6-2.2, OR(>314 microg/day) = 0.70, 0.3-1.4). We observed a reduced risk associated with the TT genotype of the child in the case-control analysis (OR(CC) = ref; for CL/P, OR(TT) = 0.54, 0.3-1.1; for CP, OR(TT) = 0.33, 0.1-1.0); this genotype, either fetal or maternal, was not statistically significant in the case-parent analysis. A frequency of TT genotype higher in our control group than previously reported in France can partly explain the risk reduction observed in case-control comparison. Interactions were not statistically significant. Stratified case-parent analysis showed, however, slight heterogeneity in the role of TT genotype according to folate intake. The modest sample size limits this study, which nonetheless provides new estimate of the possible impact of dietary folate intake and MTHFR polymorphism on oral clefts.

  20. The use of exome genotyping to predict pathological Gleason score upgrade after radical prostatectomy in low-risk prostate cancer patients.

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    Jong Jin Oh

    Full Text Available Active surveillance (AS is a promising option for patients with low-risk prostate cancer (PCa, however current criteria could not select the patients correctly, many patients who fulfilled recent AS criteria experienced pathological Gleason score upgrade (PGU after radical prostatectomy (RP. In this study, we aimed to develop an accurate model for predicting PGU among low-risk PCa patients by using exome genotyping.We genotyped 242,221 single nucleotide polymorphisms (SNPs on a custom HumanExome BeadChip v1.0 (Illuminam Inc. in blood DNA from 257 low risk PCa patients (PSA <10 ng/ml, biopsy Gleason score (GS ≤6 and clinical stage ≤T2a who underwent radical prostatectomy. Genetic data were analyzed using an unconditional logistic regression to calculate an odds ratio as an estimate of relative risk of PGU, which defined pathologic GS above 7. Among them, we selected persistent SNPs after multiple testing using FDR method, and we compared accuracies from the multivariate logistic model incorporating clinical factors between included and excluded selected SNP information.After analysis of exome genotyping, 15 SNPs were significant to predict PGU in low risk PCa patients. Among them, one SNP--rs33999879 remained significant after multiple testing. When a multivariate model incorporating factors in Epstein definition--PSA density, biopsy GS, positive core number, tumor per core ratio and age was devised for the prediction of PGU, the predictive accuracy of the multivariate model was 78.4% (95%CI: 0.726-0.834. By addition the factor of rs33999879 in aforementioned multivariate model, the predictive accuracy was 82.9%, which was significantly increased (p = 0.0196.The rs33999879 SNP is a predictor for PGU. The addition of genetic information from the exome sequencing effectively enhanced the predictive accuracy of the multivariate model to establish suitable active surveillance criteria.

  1. Relative risk regression models with inverse polynomials.

    Science.gov (United States)

    Ning, Yang; Woodward, Mark

    2013-08-30

    The proportional hazards model assumes that the log hazard ratio is a linear function of parameters. In the current paper, we model the log relative risk as an inverse polynomial, which is particularly suitable for modeling bounded and asymmetric functions. The parameters estimated by maximizing the partial likelihood are consistent and asymptotically normal. The advantages of the inverse polynomial model over the ordinary polynomial model and the fractional polynomial model for fitting various asymmetric log relative risk functions are shown by simulation. The utility of the method is further supported by analyzing two real data sets, addressing the specific question of the location of the minimum risk threshold.

  2. Association between glutathione S-transferase T1, M1, and P1 genotypes and the risk of colorectal cancer.

    Science.gov (United States)

    Cong, Ning; Liu, Lisheng; Xie, Ying; Shao, Wenbo; Song, Jinlong

    2014-11-01

    Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens. Genetic polymorphisms within the genes encoding for GSTs may therefore cause variations in their enzyme activity, which may in turn influence the interindividual susceptibility to cancers. In this study, we aimed to investigate the association between genetic polymorphisms of GSTT1, GSTM1, and GSTP1 and the risk of colorectal cancer (CRC) in 264 cases and 317 controls in a Chinese population. Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Our results showed that individuals with GSTT1 and GSTM1 null genotypes exhibited a higher risk of CRC (GSTT1, OR,1.66; 95% CI, 1.20-2.31, P=0.003; GSTM1, OR,1.57; 95% CI,1.13-2.18, P=0.007), while no association was observed for GSTP1 (P heterozygous=0.790 or P variant=0.261). Furthermore, individuals who simultaneously carried the null genotypes for both GSTT1 and GSTM1 showed a stronger risk association (OR, 1.95; 95% CI, 1.33-2.85; P<0.001). In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.

  3. Antigenic differences between the EG95-related proteins from Echinococcus granulosus G1 and G6 genotypes: implications for vaccination.

    Science.gov (United States)

    Alvarez Rojas, C A; Gauci, C G; Lightowlers, M W

    2013-02-01

    Cystic echinococcosis caused by Echinococcus granulosus remains an important and neglected issue in public health. The study of the likely efficacy of the currently available EG95 vaccine against other genotypes of the parasite is important to improve the vaccine as a potential tool to be used in control programmes. The recombinant vaccine EG95-1G1 was developed based on the G1 genotype of E. granulosus. Characterization of the eg95 gene family in the G6 genotype by genomic DNA cloning previously produced the first unequivocal information about the composition of the gene family in a different genotype. The information was used in this study to predict and express two EG95-related proteins from the G6 genotype as recombinants, for assessment of their capacity to bind antibodies raised in sheep vaccinated with the EG95-1G1 vaccine. The proteins (EG95-1G6 and EG95-5G6) from the G6 genotype of E. granulosus were unable to bind all the antibodies raised by sheep vaccinated with EG95-1G1. Differences in the amino acid sequence of EG95-related proteins from G6 and likely the differences in the encoded FnIII domain may be responsible for changes in the conformation of these epitopes.

  4. Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction

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    Seljeflot Ingebjørg

    2008-06-01

    Full Text Available Abstract Background Warfarin treatment has a narrow therapeutic range, requiring meticulous monitoring and dosage titration. Individual dosage requirement has recently partly been explained by genetic variation of the warfarin metabolizing enzyme CYP2C9 and the Vitamin K-activating enzyme VKORC1. In the WARIS-II study, comparing three different antithrombotic regimens after myocardial infarction, warfarin treatment reduced thrombotic events, but was associated with more frequent bleeding than use of acetylsalisylic acid (ASA alone. Aims The primary aim of the present study was to investigate the relation between genotypes of CYP2C9 and VKORC1 and warfarin maintenance dose in myocardial infarction. The secondary aim was to relate the genotypes to international normalized ratio (INR. Methods Genotyping was performed in 212 myocardial infarction patients from the WARIS-II study by robotic isolation of DNA from EDTA whole blood (MagNa Pure LC before PCR amplification (LightCycler and melting point analysis. Results The 420 C>T substitution of CYP2C9*2, the 1075 A>C substitution of CYP2C9*3 and the 1173 C>T substitution of VKORC1 had minor allele frequencies of, 11.3%, 5.7% and 36.6% respectively. Warfarin weekly dose varied between 17 mg and 74 mg among the patients. INR did not vary between genotypes. Warfarin dosage requirement was significantly associated with CYP2C9 and VKORC1 genotypes, treatment group and age. The VKORC1 genotype contributed 24.5% to the interindividual variation in warfarin dosage, whereas the combined CYP2C9 genotypes were only responsible for 7.2% of the dose variation. Conclusion CYP2C9 and VKORC1 genotype frequencies in myocardial infarction patients appear similar to other patient groups and have similar impact on warfarin maintenance dose.

  5. Associations of GSTM1*0 and GSTA1*A genotypes with the risk of cardiovascular death among hemodialyses patients.

    Science.gov (United States)

    Suvakov, Sonja; Damjanovic, Tatjana; Pekmezovic, Tatjana; Jakovljevic, Jovana; Savic-Radojevic, Ana; Pljesa-Ercegovac, Marija; Radovanovic, Slavica; Simic, Dragan V; Pljesa, Steva; Zarkovic, Milos; Mimic-Oka, Jasmina; Dimkovic, Nada; Simic, Tatjana

    2014-01-14

    The presence of glutathione transferase (GST) M1 null genotype (GSTM1-null) in end-stage renal disease (ESRD) patients is associated with lower overall survival rate in comparison to those with GSTM1-active variants. We examined association between GSTM1 and GSTT1 deletion polymorphisms as well as SNPs in GSTA1/rs3957357 and GSTP1/rs1695 genes with overall and cause-specific cardiovascular mortality in ESRD patients. Total of 199 patients undergoing hemodialysis were included in the study. Median value of time elapsed from dialysis initiation until the death, or the end of follow-up was 8 ± 5 years. The effect of GSTM1, GSTT1, GSTP1 and GSTA1 gene polymorphisms on predicting overall and specific cardiovascular outcomes (myocardial infarction, MI or stroke) was analyzed using Cox regression model, and differences in survival were determined by Kaplan-Meier. GSTM1-null genotype in ESRD patients was found to be independent predictor of overall and cardiovascular mortality. However, after false discovery rate and Bonferroni corrections this effect was lost. The borderline effect modification by wild-type GSTA1*A/*A genotype on associations between GSTM1-null and analyzed outcomes was found only for death from stroke. Homozygous carriers of combined GSTM1*0/GSTA1*A genotype exhibited significantly shorter time to death of stroke or MI in comparison with carriers of either GSTM1-active or at least one GSTA1*B gene variant. The best survival rate regarding cardiovascular outcome was found for ESRD patients with combined GSTM1-active and mutant GSTA1*B/*B genotype. Combined GSTM1*0/GSTA1*A genotypes might be considered as genetic markers for cardiovascular death risk in ESRD patients, which may permit targeting of preventive and early intervention.

  6. Risk aversion relates to cognitive ability

    DEFF Research Database (Denmark)

    Andersson, Ola; Holm, Håkan J.; Tyran, Jean-Robert Karl

    Recent experimental studies suggest that risk aversion is negatively related to cognitive ability. In this paper we report evidence that this relation might be spurious. We recruit a large subject pool drawn from the general Danish population for our experiment. By presenting subjects with choice...

  7. Temporal changes in HCV genotype distribution in three different high risk populations in San Francisco, California

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    Evans Jennifer

    2011-08-01

    Full Text Available Abstract Background Hepatitis C virus (HCV genotype (GT has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S. HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing. Methods We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4. Results Overall, GT 1 was predominant (72.4%, however younger injection drug users (IDU had a lower proportion of GT 1 infections (54.7% compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively. Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34. African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99. Conclusions Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level.

  8. Adiponectin Genotype, Blood Pressures, and Arterial Stiffness: The Cardiometabolic Risk in Chinese (CRC) Study.

    Science.gov (United States)

    Liang, Jun; Qiu, Qinqin; Gong, Ying; Liu, Xuekui; Dou, Lianjun; Zou, Caiyan; Wang, Yu; Qi, Lu

    2015-05-01

    The authors examined whether the adiponectin gene (ADIPOQ) variant was associated with blood pressure and arterial stiffness in Chinese adults. A genome-wide association study of the adiponectin variant rs864265 in the ADIPOQ gene was genotyped in a total of 2364 participants. After adjustment for sex, age, body mass index (BMI), fasting glucose, and lipids, participants carrying the T allele of rs864265 showed a greater increase in carotid-femoral pulse wave velocity (cfPWV) and systolic blood pressure (SBP). Further adjustment for blood pressure did not appreciably change the association with cfPWV. The authors found significant interactions between rs864265 and BMI, waist circumference, body fat percentage, and SBP in relation to cfPWV (P for interaction = .035, .001, .003, .013, respectively). The T allele of rs864265 was associated with high blood pressure and arterial stiffness. BMI, body fat percentage, waist circumference, and SBP might modify the effects of genetic polymorphism on arterial stiffness.

  9. Interactions between C-Reactive Protein Genotypes with Markers of Nutritional Status in Relation to Inflammation

    Science.gov (United States)

    Nienaber-Rousseau, Cornelie; Swanepoel, Bianca; Dolman, Robin C.; Pieters, Marlien; Conradie, Karin R.; Towers, G. Wayne

    2014-01-01

    Inflammation, as indicated by C-reactive protein concentrations (CRP), is a risk factor for chronic diseases. Both genetic and environmental factors affect susceptibility to inflammation. As dietary interventions can influence inflammatory status, we hypothesized that dietary effects could be influenced by interactions with single nucleotide polymorphisms (SNPs) in the CRP gene. We determined 12 CRP SNPs, as well as various nutrition status markers in 2010 black South Africans and analyzed their effect on CRP. Interactions were observed for several genotypes with obesity in determining CRP. Lipid intake modulated the pro-inflammatory effects of some SNPs, i.e., an increase in both saturated fatty acid and monounsaturated fatty acid intake in those homozygous for the polymorphic allele at rs2808630 was associated with a larger increase in CRP. Those harboring the minor alleles at rs3093058 and rs3093062 presented with significantly higher CRP in the presence of increased triglyceride or cholesterol intake. When harboring the minor allele of these SNPs, a high omega-6 to -3 ratio was, however, found to be anti-inflammatory. Carbohydrate intake also modulated CRP SNPs, as HbA1C and fasting glucose levels interacted with some SNPs to influence the CRP. This investigation highlights the impact that nutritional status can have on reducing the inherent genetic susceptibility to a heightened systemic inflammatory state. PMID:25393688

  10. Interactions between C-reactive protein genotypes with markers of nutritional status in relation to inflammation.

    Science.gov (United States)

    Nienaber-Rousseau, Cornelie; Swanepoel, Bianca; Dolman, Robin C; Pieters, Marlien; Conradie, Karin R; Towers, G Wayne

    2014-11-11

    Inflammation, as indicated by C-reactive protein concentrations (CRP), is a risk factor for chronic diseases. Both genetic and environmental factors affect susceptibility to inflammation. As dietary interventions can influence inflammatory status, we hypothesized that dietary effects could be influenced by interactions with single nucleotide polymorphisms (SNPs) in the CRP gene. We determined 12 CRP SNPs, as well as various nutrition status markers in 2010 black South Africans and analyzed their effect on CRP. Interactions were observed for several genotypes with obesity in determining CRP. Lipid intake modulated the pro-inflammatory effects of some SNPs, i.e., an increase in both saturated fatty acid and monounsaturated fatty acid intake in those homozygous for the polymorphic allele at rs2808630 was associated with a larger increase in CRP. Those harboring the minor alleles at rs3093058 and rs3093062 presented with significantly higher CRP in the presence of increased triglyceride or cholesterol intake. When harboring the minor allele of these SNPs, a high omega-6 to -3 ratio was, however, found to be anti-inflammatory. Carbohydrate intake also modulated CRP SNPs, as HbA1C and fasting glucose levels interacted with some SNPs to influence the CRP. This investigation highlights the impact that nutritional status can have on reducing the inherent genetic susceptibility to a heightened systemic inflammatory state.

  11. Biofilm Formation in Staphylococcus Aureus and its Relation to Phenotypic and Genotypic Criteria

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    Hasannejad Bibalan, M. (MSc

    2014-09-01

    Full Text Available Background and Objective: Biofilm is a complex microbial community embedded in a self-produced extracellular polymeric matrix. We aimed to study the extent of biofilm formation by S. Areas isolates and its relation to some phenotypic and genotypic criteria. Material and Methods: One hundred-fifty strains of Staphylococcus aureus isolated from Gorgan were studied. Microtiter plate assay method was used for investigation of biofilm formation.The biofilm formation of strains were recorded and its relation to accessory gene regulator (agr and antibiotic resistance were assessed by X2 test. Results: Eighty-four isolates (56% were able to form biofilm. The strength of biofilm formation in agr group I was more than that of other groups. The biofilm formation among S. Areas isolated from the wound and urine (both with 75 % had the highest capability. Methicillin-resistant isolates had a greater ability to biofilm formation. Conclusion: Methicillin resistant isolates had a greater ability to biofilm formation. Given the importance and treatment related problems of Methicillin-Resistant Staphylococcus Aureus (MRSA especially Community Acquired-Methicillin-Resistant Staphylococcus Aureus (CA-MRSA, it is a necessity to control or remove the biofilm formation alongside antibiotic treatment.

  12. A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

    DEFF Research Database (Denmark)

    Holmes, Michael V; Frikke-Schmidt, Ruth; Melis, Daniela

    2014-01-01

    BACKGROUND: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD). METHODS AND RESULTS: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking statu...

  13. Alcohol consumption, alcohol dehydrogenase 1C (ADH1C) genotype, and risk of colorectal cancer in the Netherlands Cohort Study on diet and cancer

    NARCIS (Netherlands)

    Bongaerts, B.W.C.; Goeij, A.F.P.M. de; Wouters, K.A.D.; Engeland, M. van; Gottschalk, R.W.H.; Schooten, F.J. van; Goldbohm, R.A.; Brandt, P.A. van den; Weijenberg, M.P.

    2011-01-01

    Within the Netherlands Cohort Study (1986), we examined associations between alcohol consumption, the alcohol dehydrogenase 1C (ADH1C) genotype, and risk of colorectal cancer (CRC). After a follow-up period of 7.3 years, 594 CRC cases with information on genotype and baseline alcohol intake were

  14. Cancer risks related to electricity production.

    Science.gov (United States)

    Boffetta, P; Cardis, E; Vainio, H; Coleman, M P; Kogevinas, M; Nordberg, G; Parkin, D M; Partensky, C; Shuker, D; Tomatis, L

    1991-01-01

    The International Agency for Research on Cancer has previously evaluated the cancer risks associated with fossil fuel-based industrial processes such as coal gastification and coke production, substances and mixtures such as coal tars, coal tar pitch and mineral oils, and a number of substances emitted from fossil-fuelled plants such as benzo[a]pyrene and other polycyclic aromatic hydrocarbons, arsenic, beryllium, cadmium, chromium, nickel, lead and formaldehyde. Based on these evaluations and other evidence from the literature, the carcinogenic risks to the general population and occupational groups from the fossil fuel cycle, the nuclear fuel cycle and renewable cycles are reviewed. Cancer risks from waste disposal, accidents and misuses, and electricity distribution are also considered. No cycle appears to be totally free from cancer risk, but the quantification of the effects of such exposures (in particular of those involving potential exposure to large amounts of carcinogens, such as coal, oil and nuclear) requires the application of methods which are subject to considerable margins of error. Uncertainties due to inadequate data and unconfirmed assumptions are discussed. Cancer risks related to the operation of renewable energy sources are negligible, although there may be some risks from construction of such installations. The elements of knowledge at our disposal do not encourage any attempt toward a quantitative comparative risk assessment. However, even in the absence of an accurate quantification of risk, qualitative indication of carcinogenic hazards should lead to preventive measures.

  15. Features of coronary heart disease development in emergency workers of the Chornobyl accident depending on the action of radiation and non radiation risk factors and genotypes of single nucleotide polymorphism rs966221 of phosphodiesterase 4D gene.

    Science.gov (United States)

    Belyi, D; Pleskach, G; Nastina, O; Sidorenko, G; Kursina, N; Bazyka, O; Kovalev, O; Chumak, A; Abramenko, I

    2016-12-01

    This study devoted to specific features of coronary heart disease (CHD) development in emergency work ers (EW) of the accident at the Chernobyl nuclear power plant (ChNPP) based on analysis the interaction between radiation and non radiation risk factors and single nucleotide polymorphism (SNP) rs966221 of phosphodiesterase (PDE) 4D gene. It was examined 397 men with CHD, including 274 EW of 1986-1987 and 123 non irradiated persons (con trol group) who were 66±10 and 69±11 years old relatively. The program studies included clinical examination, elec trocardiography (ECG), ECG daily monitoring, ECG stress testing, echo doppler cardiography, analysis of serum lipid spectrum, polymerase chain reaction with restriction of reaction products, retrospective analysis of case histories. Diagnosis of CHD or its approval was carried out in accordance with the standards of diagnosis, accepted in Ukraine. All EW before their taking part in cleaning ChNPP territory did not suffered from CHD. According to the analysis of contingency tables, carriers of the TT genotype of rs966221 increased the risk of myocardial infarction (MI) in 2.538 times compared with carriers of genotypes CC and CT. The use of Kaplan Meier method showed that a half of EW with the TT genotype developed MI before 64 years old, while with the other geno types up to 78.7 years old. In the control group statistically significant increase of cumulative proportion of patients with MI, carriers of the TT genotype, began from 60 years old. Compared to the non irradiated patients EW fell ill with CHD on 9.4 years earlier. Using proportional hazards analysis (Cox regression), it was found that EW had 3.9 times higher risk of CHD than in non irradiated individuals. Smoking and overweight brought three times less but significant risk - 1.37 and 1.33 respectively. The TT genotype unlike genotypes CC and CT gene PDE4D increased risk of MI in 1.757 times more both in EW and control group. The risk of CHD development was

  16. Bladder cancer risk associated with genotypic polymorphism of the matrix metalloproteinase-1 and 7 in North Indian population.

    Science.gov (United States)

    Srivastava, Priyanka; Gangwar, Ruchika; Kapoor, Rakesh; Mittal, Rama D

    2010-01-01

    Matrix metalloproteinases (MMPs) contribute to tumor invasion and microenvironment, hence are associated with bladder cancer risk. We therefore, tested whether polymorphisms in MMP genes modify the risk of bladder cancer (BC) and whether smoke exposure modifies this risk. Genotyping was performed in 200 BC patients and 200 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MMP1-1607 2G/2G and MMP7-181 GG genotype were associated with increased risk of BC (p BCG) treated non muscle invasive BC (NMIBC) patients (log rank p, 0.030). Our data suggested that MMP1-1607 2G and MMP7-181 G allele were associated with high risk of BC, which was quite evident amongst smokers too. BCG treated NMIBC patients reflected protective effect for 2G allele carrier (1G/2G + 2G/2G) of MMP1-1607. This study provided new support for the association of MMP1-1607 and MMP7-181 in bladder cancer development, the tumorigenic effect of which was observed to be more enhanced in case of tobacco exposure.

  17. Prevalence of HBV genotypes in South American immigrants affected by HBV-related chronic active hepatitis

    Directory of Open Access Journals (Sweden)

    Emilio Palumbo

    2007-06-01

    Full Text Available This study evaluated the prevalence of HBV infection in a population of South American immigrants in Italy and to determine in patients with detectable serum HBV-DNA the HBVgenotypes. Between April 2005 and April 2006 a total of 130 South American immigrants were tested for HBsAg. In HBsAg positive patients the biochemical and virological activity of infection and the possible presence of co-infections (HCV, HDV, HIV were evaluated. In patients with detectable serum HBV DNA, the HBV genotype was determined by INNOLiPA. Among the 130 subjects tested, 14 (10.7% resulted HBsAg positive. All were men, with a mean age of 22 years (range 19-37 and 12 (85.7 % came from Brazil, while 2 (14.3% came from Ecuador. All patients infected by HBV had elevated alanine-aminotransferase serum levels (mean level was 127 IU/L, range 74-312 and serum HBV DNA detectable by PCR-Real Time (mean level 1,037,652 copies/mL, range 19,876-1,377,648. Genotype distribution was as follow: genotype D, 9 (64.2%, genotype A, 5 (35.8%. All patients infected by genotype D came from Brazil, while among the patients infected by genotype A, three came from Brazil and two from Ecuador. Our study evidences a moderate prevalence of HBV-infection in South American immigrants with the identification of two genotypes, D and A. These genotypes are not the most prevalent in the South America and this is probably the expression of a possible geographical redistribution of HBV genotypes.

  18. Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region

    DEFF Research Database (Denmark)

    Lusk, Christine M; Dyson, Greg; Clark, Andrew G;

    2014-01-01

    Markers of the chromosome 9p21 region are regarded as the strongest and most reliably significant genome-wide association study (GWAS) signals for Coronary heart disease (CHD) risk; this was recently confirmed by the CARDIoGRAMplusC4D Consortium meta-analysis. However, while these associations...... genotypes in the 9p21 region were strongest in a sub-group of hypertensives. We subsequently validated the effect of the region in an independent sample from the Copenhagen City Heart Study. Our study suggests that marker SNPs identified as predictors of CHD risk in large population based GWAS may have...... their greatest utility in explaining risk of disease in particular sub-groups characterized by biological and environmental effects measured by the traditional CHD risk factors....

  19. Changes of Chlorophyll Index (SPAD, Relative Water Content, Electrolyte Leakage and Seed Yield in Spring Safflower Genotypes under Irrigation Termination

    Directory of Open Access Journals (Sweden)

    B.E. Moosavifar

    2012-04-01

    Full Text Available In order to evaluate the effect of irrigation termination and genotype on chlorophyll index (SPAD, relative water content, electrolyte leakage and seed yield in spring safflower, an experiment was conducted, in a spilt plot arrangement based on randomized complete block design with four replications at Research Farm, Faculty of Agriculture, the University of Birjand, during 2008. Irrigation regimes (full irrigation (whole season irrigation, irrigation until grain filling, flowering and heading-bud and genotypes (Mahali Isfahan (a local variety, Isfahan28 and IL111 were arranged in main and subplots, respectively. Results showed chlorophyll content, relative water content, cell membrane stability and seed yield were influenced by irrigation termination. Provided that with terminating irrigation at an earlier stage, an increase in electrolyte leakage and reduction in relative water content and seed yield was observed in plants. There were negative relations between electrolyte leakage from plants leaf cells and seed yield. Plants which experienced irrigation termination in an earlier growth stage, suffered more damage to their cell membranes, leading to depression of their production potential. Based on the results, Mahali Isfahan and Isfahan28 can be introduced as drought resistant genotypes, because of their lower electrolyte leakage and higher relative water content. But, in general, Mahali Isfahan had the highest seed yield due to its nativeness and high adaptation to arid conditions southern of Khorasan, and therefore this genotype suggests for planting in the region.

  20. High-Density Genotyping of Immune Loci in Koreans and Europeans Identifies Eight New Rheumatoid Arthritis Risk Loci

    Science.gov (United States)

    Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Yoo, Dae Hyun; Kang, Young Mo; Kim, Seong-Kyu; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Choe, Jung-Yoon; Shin, Hyoung Doo; Lee, Jong-Young; Han, Bok-Ghee; Nath, Swapan K.; Eyre, Steve; Bowes, John; Pappas, Dimitrios A.; Kremer, Joel M.; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlestig, Lisbeth; Okada, Yukinori; Diogo, Dorothée; Liao, Katherine P.; Karlson, Elizabeth W.; Raychaudhuri, Soumya; Rantapää-Dahlqvist, Solbritt; Martin, Javier; Klareskog, Lars; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Greenberg, Jeffrey D.; Plenge, Robert M.; Bae, Sang-Cheol

    2015-01-01

    Objective A highly polygenic etiology and high degree of allele-sharing between ancestries have been well-elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analyzed Korean rheumatoid arthritis case-control samples using the Immunochip and GWAS array to search for new risk alleles of rheumatoid arthritis with anti-citrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data, for a total sample size of 9,299 Korean and 45,790 European case-control samples. Results We identified 8 new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1–FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10−8), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the 7 new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of SNPs that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusion This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases. PMID:24532676

  1. High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci.

    Science.gov (United States)

    Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Yoo, Dae Hyun; Kang, Young Mo; Kim, Seong-Kyu; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Choe, Jung-Yoon; Shin, Hyoung Doo; Lee, Jong-Young; Han, Bok-Ghee; Nath, Swapan K; Eyre, Steve; Bowes, John; Pappas, Dimitrios A; Kremer, Joel M; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlestig, Lisbeth; Okada, Yukinori; Diogo, Dorothée; Liao, Katherine P; Karlson, Elizabeth W; Raychaudhuri, Soumya; Rantapää-Dahlqvist, Solbritt; Martin, Javier; Klareskog, Lars; Padyukov, Leonid; Gregersen, Peter K; Worthington, Jane; Greenberg, Jeffrey D; Plenge, Robert M; Bae, Sang-Cheol

    2015-03-01

    A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45,790 European case-control samples. We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Elevated carbon dioxide alters the relative fitness of Taraxacum officinale genotypes

    Science.gov (United States)

    I tested whether elevated carbon dioxide concentration differentially affected which genotypes of the apomictic species dandelion produced the largest number of viable seeds in two different field experiments, and identified morphological and physiological traits associated with fitness at elevated ...

  3. Catechol-O-methyltransferase (COMT Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Stephan Heinzel

    2014-01-01

    Full Text Available Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years and 25 older (aged 60–75 years healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P<.001, which was larger in younger as compared to older adults (P<.001. Age-related differences were qualified by an interaction with COMT genotype (P<.001, and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism.

  4. Catechol-O-methyltransferase (COMT) Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

    Science.gov (United States)

    Riemer, Thomas G.; Schulte, Stefanie; Onken, Johanna; Heinz, Andreas; Rapp, Michael A.

    2014-01-01

    Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years) and 25 older (aged 60–75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism. PMID:24772423

  5. Genotype by environment interactions in relation to growth traits in slow growing chickens

    Directory of Open Access Journals (Sweden)

    Beaumont Catherine

    2007-09-01

    Full Text Available Abstract Since feed conversion ratio (FCR is higher in slow-growing "Label Rouge" chickens than in broiler chickens, it is important to work on its improvement in this breed. However, this involves rearing animals in cages (C, an environment very different from that used for selection (in floor pens, S and production (outdoor, E. The aim of this study was to evaluate the importance of genotype by environment (G × E interactions between S, C, and E environments, to find the best way to select for FCR, using 2002 related animals. Growth curve parameters were estimated and body composition measured. Individual feed conversion ratios (FCR were recorded between 8 and 10 weeks in C. The presence of G × E interactions was assessed by the genetic correlations between the same trait recorded in different environments. Moderate but significant G × E interactions were detected for carcass traits, a significant one was observed between E and S or C for growth curve parameters but none between C and S. If G × E interactions are set aside, i.e. selecting on traits recorded in C, abdominal fatness is the best indirect selection criterion for FCR but if they are taken in account then leg yield or growth curve parameters in S and growth curve parameters in E are better.

  6. Genotypic and phenotypic presentation of transthyretin-related familial amyloid polyneuropathy (TTR-FAP) in Turkey.

    Science.gov (United States)

    Durmuş-Tekçe, Hacer; Matur, Zeliha; Mert Atmaca, Murat; Poda, Mehves; Çakar, Arman; Hıdır Ulaş, Ümit; Oflazer-Serdaroğlu, Piraye; Deymeer, Feza; Parman, Yesim G

    2016-07-01

    Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder caused by mutations of the transthyretin (TTR) gene. The mutant amyloidogenic transthyretin protein causes the systemic accumulation of amyloid fibrils that result in organ dysfunction. TTR-associated FAP is a progressive and fatal disease, if left untreated, and should be considered in the differential diagnosis of any person presenting with a progressive polyneuropathy, particularly with accompanying autonomic involvement. The clinical, electrophysiological, histopathological, and genetic characteristics of 17 patients from Turkey (5 female, 13 male) from nine families with polyneuropathy and mutations in TTR were evaluated. Sequence analysis of the TTR gene revealed five mutations (Val30Met, Glu89Gln, Gly53Glu, Glu54Gly and Gly47Glu). Mean age at disease onset was 40.4 ± 13.9 years (range 21-66 years). The most commonly reported initial complaint was paresthesia in the feet (asymmetric in three patients). Three patients (2 male) with the Glu89Gln mutation presented with carpal tunnel syndrome. Two patients with the Gly53Glu mutation showed episodes of dysarthria and hemiparesis, consistent with this genotype. Seven patients died during the period of follow-up as a result of systemic involvement. Our study suggests that a cohort of patients from Turkey with TTR-FAP exhibits clinical and genetic heterogeneity.

  7. Resting-state brain and the FTO obesity risk allele: default mode, sensorimotor and salience network connectivity underlying different somatosensory integration and reward processing between genotypes.

    Directory of Open Access Journals (Sweden)

    Gaia eOlivo

    2016-02-01

    Full Text Available Single-nucleotide polymorphisms (SNPs of the fat mass and obesity associated (FTO gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN, sensorimotor (SMN, and salience network (SN in thirty male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS and Behavioral Activation System (BAS questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr accounting for features of both scores. A prominence of BIS over BAS (higher BBr resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.

  8. Combinations of genetic data in a study of neuroblastoma risk genotypes

    DEFF Research Database (Denmark)

    Capasso, Mario; Calabrese, Francesco Maria; Iolascon, Achille;

    2014-01-01

    Analysis of combinations of genetic changes that occur exclusively in patients may be a supplementary strategy to the single-locus strategy used in many genetic studies. The genotypes of 16 SNPs within susceptibility loci for neuroblastoma (NB) were analyzed in a previous study. In the present st...

  9. Risk Perception Related to Critical Infrastructure

    Directory of Open Access Journals (Sweden)

    Badea Dorel

    2016-06-01

    Full Text Available Through this article it is brought to attention the essential aspects related to the perceived risks for critical infrastructure, both theoretically and practically, considering perception as an important input in the risk management process. For the practical part, the added value component in the field consists from the results of research based on survey, conducted in a wider framework of determining the level of awareness of the critical infrastructure issue by a pilot sample, consisting of persons with managerial and operational attributions in this sector.

  10. Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet's disease susceptibility.

    Science.gov (United States)

    Takeuchi, Masaki; Mizuki, Nobuhisa; Meguro, Akira; Ombrello, Michael J; Kirino, Yohei; Satorius, Colleen; Le, Julie; Blake, Mary; Erer, Burak; Kawagoe, Tatsukata; Ustek, Duran; Tugal-Tutkun, Ilknur; Seyahi, Emire; Ozyazgan, Yilmaz; Sousa, Inês; Davatchi, Fereydoun; Francisco, Vânia; Shahram, Farhad; Abdollahi, Bahar Sadeghi; Nadji, Abdolhadi; Shafiee, Niloofar Mojarad; Ghaderibarmi, Fahmida; Ohno, Shigeaki; Ueda, Atsuhisa; Ishigatsubo, Yoshiaki; Gadina, Massimo; Oliveira, Sofia A; Gül, Ahmet; Kastner, Daniel L; Remmers, Elaine F

    2017-03-01

    We analyzed 1,900 Turkish Behçet's disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated SNP was rs1050502, a tag SNP for HLA-B*51. In the Turkish discovery set, we identified three new risk loci, IL1A-IL1B, IRF8, and CEBPB-PTPN1, with genome-wide significance (P < 5 × 10(-8)) by direct genotyping and ADO-EGR2 by imputation. We replicated the ADO-EGR2, IRF8, and CEBPB-PTPN1 loci by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls further replicated ADO-EGR2 and IRF8, and meta-analysis additionally identified RIPK2 and LACC1. The disease-associated allele of rs4402765, the lead marker at IL1A-IL1B, was associated with both decreased IL-1α and increased IL-1β production. ABO non-secretor genotypes for two ancestry-specific FUT2 SNPs showed strong disease association (P = 5.89 × 10(-15)). Our findings extend the list of susceptibility genes shared with Crohn's disease and leprosy and implicate mucosal factors and the innate immune response to microbial exposure in Behçet's disease susceptibility.

  11. Coffee consumption and CYP1A2 genotype in relation to bone mineral density of the proximal femur in elderly men and women: a cohort study

    Directory of Open Access Journals (Sweden)

    Lind Lars

    2010-02-01

    Full Text Available Abstract Background Drinking coffee has been linked to reduced calcium conservation, but it is less clear whether it leads to sustained bone mineral loss and if individual predisposition for caffeine metabolism might be important in this context. Therefore, the relation between consumption of coffee and bone mineral density (BMD at the proximal femur in men and women was studied, taking into account, for the first time, genotypes for cytochrome P450 1A2 (CYP1A2 associated with metabolism of caffeine. Methods Dietary intakes of 359 men and 358 women (aged 72 years, participants of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, were assessed by a 7-day food diary. Two years later, BMD for total proximal femur, femoral neck and trochanteric regions of the proximal femur were measured by Dual-energy X-ray absorptiometry (DXA. Genotypes of CYP1A2 were determined. Adjusted means of BMD for each category of coffee consumption were calculated. Results Men consuming 4 cups of coffee or more per day had 4% lower BMD at the proximal femur (p = 0.04 compared with low or non-consumers of coffee. This difference was not observed in women. In high consumers of coffee, those with rapid metabolism of caffeine (C/C genotype had lower BMD at the femoral neck (p = 0.01 and at the trochanter (p = 0.03 than slow metabolizers (T/T and C/T genotypes. Calcium intake did not modify the relation between coffee and BMD. Conclusion High consumption of coffee seems to contribute to a reduction in BMD of the proximal femur in elderly men, but not in women. BMD was lower in high consumers of coffee with rapid metabolism of caffeine, suggesting that rapid metabolizers of caffeine may constitute a risk group for bone loss induced by coffee.

  12. Risk factors for age-related maculopathy.

    LENUS (Irish Health Repository)

    Connell, Paul P

    2012-02-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715\\/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  13. HLA-G 14-bp Ins/Ins Genotype in Patients Harbouring Helicobacter pylori Infection: A Potential Risk Factor?

    Science.gov (United States)

    Genre, J; Reginaldo, F P Santos; Andrade, J Marco de Leon; Lima, F P; da Camara, A V Coutinho; Donadi, E A; Crispim, J C

    2016-01-01

    H. pylori is a potent pathogen due to its capacity to successfully evade host defence mechanisms. Despite inducing immune responses in infected individuals, sometimes these responses fail to clear the infection and the bacterium establishes a persistent infection leading to chronic inflammation. In this context, we hypothesized that human leucocyte antigen G (HLA-G), a non-classical major histocompatibility complex molecule that has the ability to regulate immune responses both in physiological and in pathological conditions, may play an important role in promoting tolerance and helping H. pylori to subvert host defence and consequently establish a chronic infection. Therefore, we evaluated the expression of HLA-G 14-bp Ins/Del polymorphism in patients harbouring H. pylori infection, as well as their relationship with histological and demographic variables, to gain a better understanding of the actual role of HLA-G and its genetic polymorphisms in bacterial infection. Sixty-eight patients with clinical symptoms suggestive of H. pylori infection were enrolled to assess HLA-G 14-bp Ins/Del polymorphism allele and genotype frequencies. After adjustment for covariates (age and gender), the odds of having the genotype Ins/Ins, compared to Del/Del, were 3.77 times greater among HP+ cases than among controls. These findings suggest that the 14-bp Ins/Ins genotype, already associated with inflammatory and autoimmune diseases as well as some viral and parasitic infections, could confer a greater risk of developing H. pylori infection.

  14. Salinity induced changes in water relations, oxidative damage and morpho-physiological adaptations of pistachio genotypes in soilless culture

    Directory of Open Access Journals (Sweden)

    Zahra Mirfattahi

    2017-09-01

    Full Text Available Selecting salt tolerant rootstocks is a sustainable approach for developing fruit trees in salinity prone areas. 60-day-old seedlings of Pistacia vera ‘Akbari’ and ‘Ghazvini’, and P. vera ‘Ghazvini’ × P. atlantica (G×A were subjected to 0, 50, 100 and 150 mM NaCl in half strength Hoagland’s nutrient solution. After 45 days, the growth, water relations, and oxidative damage parameters were investigated. Salt stress reduced plant biomass, height, crown diameter and leaf number, but increased specific leaf area (SLA of the seedlings. Under salt stress, the growth of ‘Akbari’ seedlings was higher than the other genotypes. Accumulation of malondialdehyde (MDA and proline was observed in the leaves of salt affected seedlings. ‘Ghazvini’ seedlings had the highest MDA concentration and the lowest cell membrane stability in their leaves. Degredation of photosynthetic pigments under salt stress was lower in the leaves of ‘Akbari’ seedlings than that in other genotypes. Increase in leaf succulence was observed in ‘Akbari’ and G×A seedlings in response to salt stress. Relative water content and concentration of anthocyanins in the leaves of pistachio genotypes remained unchanged under salt stress. The results revealed that monitoring leaf abscission, SLA, leaf succulence, MDA concentration, and photosynthetic pigments provide suitable contrast for screening salt tolerance in pistachio. Furthuremore, ‘Akbari’ was found to be the most salt tolerant genotype.

  15. Prevalences, Genotypes, and Risk Factors for HIV Transmission in South America

    Science.gov (United States)

    2005-02-07

    Alava A, et al. HIV-1 genotype diversity in South America [abstract TuPeC4812]. In: Abstracts of the XIV Interna - tional AIDS Conference; 2002...University of Antioquia, Medellin, Colombia; Aracely Alava and Carlos Mosquera, Instituto Nacional de Higiene y Medicina Tropical ‘‘Leopoldo Izquieta Perez...Nacional de Enfermedades Tropicales (CENETROP), Santa Cruz, Bolivia; Adolfo H. Galeano, Instituto de Medicina Tropical (IMT), Asuncion, Paraguay; Jose C

  16. Photosynthesis, water relations, and growth of two hybrid Populus genotypes during a severe drought

    Energy Technology Data Exchange (ETDEWEB)

    Dickmann, D.I.; Liu, Zuijun; Nguyen, Phu V.; Pregitzer, K.S. (Michigan State Univ., East Lansing, MI (USA))

    1992-01-01

    During the 1988 growing season in East Lansing, Michigan, only 1.53 cm of rain fell from mid-May to mid-July, causing a severe drought. Then, a period of near record precipitation commenced; 30.4 cm of rain fell from July 19 to October 4. Growth, photosynthesis, and water relations of hybrid poplar cultivars Eugenei and Tristis, which had been established in the spring of 1987 in plastic pots buried in the ground, were measured on several sunny days during the 1988 growing season. Pots were irrigated at two different rates, and half the pots received supplemental nitrogen fertilizer. On a seasonal basis, photosynthesis and water-use efficiency in both genotypes peaked in early July and declined thereafter. Stomatal conductances were low during the drought but increased substantially when the rains commenced. Whereas nitrogen level had little effect on leaf physiology, the low water treatment produced significant reductions in photosynthesis and conductance. Diurnal measurements were made on June 17 and July 12. On both days photosynthesis and conductances were higher in Tristis than in Eugenei, especially for plants in the high water treatments and on July 12, the most extreme period of the drought. Drought produced both stomatal and mesophyll limitations to photosynthesis in both clones, though these responses were more pronounced in Eugenei. This clone also showed very low water-use efficiencies in the low water treatment on July 12. Even though the physiology of Eugenei was more impacted by drought than Tristis, it still produced two to three times more biomass over the 2-year period of the study than did Tristis. 41 refs., 10 figs., 5 tabs.

  17. High osteoporosis risk among East Africans linked to lactase persistence genotype.

    Science.gov (United States)

    Hilliard, Constance B

    2016-01-01

    This ecological correlation study explores the marked differential in osteoporosis susceptibility between East and West Africans. African tsetse belt populations are lactase non-persistent (lactose intolerant) and possess none of the genetic polymorphisms carried by lactase persistent (lactose tolerant) ethnic populations. What appears paradoxical, however, is the fact that Niger-Kordofanian (NK) West African ethnicities are also at minimal risk of osteoporosis. Although East Africans share a genetic affinity with NK West Africans, they display susceptibility rates of the bone disorder closer to those found in Europe. Similar to Europeans, they also carry alleles conferring the lactase persistence genetic traits. Hip fracture rates of African populations are juxtaposed with a global model to determine whether it is the unique ecology of the tsetse-infested zone or other variables that may be at work. This project uses MINITAB 17 software for regression analyses. The research data are found on AJOL (African Journals Online), PUBMED and JSTOR (Scholarly Journal Archive). Data showing the risk of osteoporosis to be 80 times higher among East Africans with higher levels of lactase persistence than lactase non-persistence West Africans are compared with global statistics. Hip fracture rates in 40 countries exhibit a high Pearson's correlation of r=0.851, with P-value=0.000 in relation to dairy consumption. Lower correlations are seen for hip fracture incidence vis-à-vis lactase persistence, per capita income and animal protein consumption. Ethnic populations who lack lactase persistence single-nucleotide polymorphisms may be at low risk of developing osteoporosis.

  18. GST null genotype and antioxidants: Risk indicators for oral pre-cancer and cancer

    Directory of Open Access Journals (Sweden)

    Bathi Renuka

    2009-01-01

    Full Text Available Objectives : This study was undertaken to detect the gene polymorphism of detoxification enzymes and estimate the antioxidant enzyme status in patients with oral cancer, oral leukoplakia and oral submucous fibrosis (OSF. Materials and Methods : The GSTM1 and GSTT1 gene polymorphism was evaluated using polymerase chain reaction; the antioxidant enzyme was estimated using biochemical methods. Statistical analyses were performed using student t-test and odds-ratio to estimate relative risk (RR. Results : The RR at 95% confidence interval (CI for GSTM1 and GSTT1 was statistically significant for all groups. The mean values of glutathione were significantly raised in all groups. The mean values of ceruloplasmin and malonaldehyde was statistically significant among cancer and OSF patients but was insignificant in smokers and cases with leukoplakia. Conclusion : Several genes perform the same function which implies the need to test for several genetic polymorphisms to identify individuals at high risk. The level of antioxidant enzymes correlate with the degree of oxidative damage. The need for further studies is emphasised.

  19. Estrogen metabolism genotypes, use of long-term hormone replacement therapy and risk of postmenopausal breast cancer.

    Science.gov (United States)

    Cerne, Jasmina Ziva; Novakovic, Srdjan; Frkovic-Grazio, Snjezana; Pohar-Perme, Maja; Stegel, Vida; Gersak, Ksenija

    2011-08-01

    Association between long-term hormone replacement therapy (HRT) use and increased risk of breast cancer is still under debate. Functionally relevant genetic variants within the estrogen metabolic pathway may alter exposure to exogenous sex hormones and affect the risk of postmenopausal breast cancer. We investigated the associations of common polymorphisms in 4 genes encoding key proteins of the estrogen metabolic pathway, duration of HRT use and their interactions with breast cancer risk. We studied 530 breast cancer cases and 270 controls of the same age and ethnicity participating in a case-control study of postmenopausal women. Duration of HRT use was ascertained through a postal questionnaire. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695) and MnSOD (rs4880) polymorphisms by PCR-based RFLP and TaqMan® allelic discrimination method. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression analysis. HRT use was significantly associated with decreased breast cancer risk (pC and HRT use (pinteraction=0.036); the risk of breast cancer associated with long-term vs. short-term HRT use was decreased in women homozygous for the wild-type allele and increased in women with at least one variant allele of the MnSOD 47T>C polymorphism. Our results suggest that MnSOD 47T>C polymorphism in interaction with long-term HRT use may modify the risk of breast cancer.

  20. A case–control study on the effect of Apolipoprotein E genotypes on gastric cancer risk and progression

    Directory of Open Access Journals (Sweden)

    De Feo Emma

    2012-10-01

    Full Text Available Abstract Background Apolipoprotein E (ApoE is a multifunctional protein playing both a key role in the metabolism of cholesterol and triglycerides, and in tissue repair and inflammation. The ApoE gene (19q13.2 has three major isoforms encoded by ε2, ε3 and ε4 alleles with the ε4 allele associated with hypercholesterolemia and the ε2 allele with the opposite effect. An inverse relationship between cholesterol levels and gastric cancer (GC has been previously reported, although the relationship between apoE genotypes and GC has not been explored so far. Methods One hundred and fifty-six gastric cancer cases and 444 hospital controls were genotyped for apoE polymorphism (ε2, ε3, ε4 alleles. The relationship between GC and putative risk factors was measured using the adjusted odds ratios (ORs and their 95% confidence intervals (CIs from logistic regression analysis. A gene-environment interaction analysis was performed. The effect of the apoE genotypes on survival from GC was explored by a Kaplan–Meier analysis and Cox proportional hazard regression model. Results Subjects carrying at least one apoE ε2 allele have a significant 60% decrease of GC risk (OR=0.40, 95% CI: 0.19 – 0.84 compared with ε3 homozygotes. No significant interaction emerged between the ε4 or ε2 allele and environmental exposures, nor ε2 or ε4 alleles affected the median survival times, even after correcting for age, gender and stadium. Conclusions Our study reports for the first time a protective effect of the ε2 allele against GC, that might be partly attributed to the higher antioxidant properties of ε2 compared with the ε3 or ε4 alleles. Given the study’s sample size, further studies are required to confirm our findings.

  1. Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Tsuchihashi T

    2014-12-01

    Full Text Available Takashi Tsuchihashi,1 Keisuke Mori,1 Kuniko Horie-Inoue,2 Yasushi Okazaki,3 Takuya Awata,4,5 Satoshi Inoue,2 Shin Yoneya1 1Department of Ophthalmology, 2Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Division of Translational Research, Research Center for Genomic Medicine, 4Division of Endocrinology and Diabetes, Department of Medicine, 5Division of RI Laboratory, Biomedical Research Center, Saitama Medical University, Iruma, Saitama, Japan Background: This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT for age-related macular degeneration (AMD.Methods: The study included 149 patients with exudative AMD treated by PDT. Eight phenotypic factors and ten genotypic factors for three single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996 in the complement factor H (CFH gene, rs 11200638-SNP in the high temperature requirement A-1 (HTRA1 gene, two SNPs (rs699947, rs2010963 in the vascular endothelial growth factor (VEGF gene, and four SNPs (rs12948385, rs12150053, rs9913583, rs1136287 in the pigment epithelium-derived factor (PEDF gene were evaluated. Results: A significant association with best-corrected visual acuity change was demonstrated in the greatest linear dimension, presence or absence of pigment epithelial detachment, and HTRA1-rs11200638 genotype statistically (P=3.67×10-4, 1.95×10-2, 1.24×10-3, respectively. Best-corrected visual acuity in patients with AA genotype of HTRA1-rs11200638 significantly decreased compared with that in patients with GG genotype (P=1.33×10-3. Logistic regression analyses demonstrated HTRA1-rs11200638 genotype was most strongly associated with best-corrected visual acuity outcome from baseline at 12 months after photodynamic therapy (P=4.60×10-3; odds ratio 2.363; 95% confidence interval 1.303–4.285.Conclusion: The HTRA1

  2. Potassium accumulation and translocation among rice genotypes in relation to internal potassium use efficiency (IKUE)

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ Abiotic stresses including potassium deficiency are limiting factors for increasing rice yield. Nine rice genotypes (Oryza Sativa L., indica) differing in sensitivity to low K stress selected from 200 volume-solution screening were used in this study to examine accumulation and translocation of K.

  3. Correlation between relatives given complete genotypes: from identity by descent to identity by function.

    Science.gov (United States)

    Sverdlov, Serge; Thompson, Elizabeth A

    2013-09-01

    In classical quantitative genetics, the correlation between the phenotypes of individuals with unknown genotypes and a known pedigree relationship is expressed in terms of probabilities of IBD states. In existing approaches to the inverse problem where genotypes are observed but pedigree relationships are not, dependence between phenotypes is either modeled as Bayesian uncertainty or mapped to an IBD model via inferred relatedness parameters. Neither approach yields a relationship between genotypic similarity and phenotypic similarity with a probabilistic interpretation corresponding to a generative model. We introduce a generative model for diploid allele effect based on the classic infinite allele mutation process. This approach motivates the concept of IBF (Identity by Function). The phenotypic covariance between two individuals given their diploid genotypes is expressed in terms of functional identity states. The IBF parameters define a genetic architecture for a trait without reference to specific alleles or population. Given full genome sequences, we treat a gene-scale functional region, rather than a SNP, as a QTL, modeling patterns of dominance for multiple alleles. Applications demonstrated by simulation include phenotype and effect prediction and association, and estimation of heritability and classical variance components. A simulation case study of the Missing Heritability problem illustrates a decomposition of heritability under the IBF framework into Explained and Unexplained components.

  4. Age-related Infection with Cryptosporidium Species and Genotype in Pigs in China

    Institute of Scientific and Technical Information of China (English)

    YIN Jian Hai; YUAN Zhong Ying; CAI Hui Xia; SHEN Yu Juan; JIANG Yan Yan; ZHANG Jing; WANG Yan Juan; CAO Jian Ping

    2013-01-01

    Objective Pigs, as hosts of zoonotic Cryptosporidium species/genotypes, are domestic animals with public health significance. The present study was to characterize the infection rate and species/genotype of Cryptosporidium in pre-weaned and post-weaned pigs from Shanghai and Shaoxing, China. Methods A total of 208 fecal samples (42 from pre-weaned piglets, and 166 from post-weaned pigs) were examined by nested PCR of the 18S rRNA gene and analyzed by phylogenetic DNA fragment sequencing of secondary PCR products. Results Infection was detected in 79 samples (19/42 pre-weaned piglets, and 60/166 post-weaned pigs). C. suis (14/79) and Cryptosporidium pig genotype II (65/79) were identified; piglets were more susceptible to the former (13/14) and post-weaned pigs to the latter (59/65). Conclusion Infection of Cryptosporidium spp. in pigs was age-specific;piglets were more susceptible to C. suis while pigs were more susceptible to Cryptosporidium pig genotype II. These findings combined with the isolation of the two Cryptosporidium from water suggest that pigs may be a source of zoonotic Cryptosporidium water pollution. Improvements in pig feeding practices, sewage discharge, feces disposal and field worker protection are therefore important to prevent potential public health problems.

  5. The Phenotypic and Genotypic Relation between Working Memory Speed and Capacity

    Science.gov (United States)

    Polderman, Tinca J. C.; Stins, John F.; Posthuma, Danielle; Gosso, M. Florencia; Verhulst, Frank C.; Boomsma, Dorret I.

    2006-01-01

    This study examined the phenotypic and genotypic relationship between working memory speed (WMS) and working memory capacity (WMC) in 12-year-old twins and their siblings (N = 409). To asses WMS all children performed a reaction time task with three memory loads from which a basic mental speed measure and the derived slope were used. WMC was…

  6. High risk human papillomavirus genotyping in clinical samples: evaluation of different commercial tests.

    Science.gov (United States)

    Paolini, F; Rollo, F; Brandi, R; Benevolo, M; Mariani, L; Cercato, M C; Vocaturo, A; Venuti, A

    2011-01-01

    The aim of the present study is to compare the performance of several commercial human papillomavirus (HPV) tests in a cohort of 281 women. The hybrid capture II, the PreTect-HPV-Proofer, the linear array, and DR.HPVTMIVD were utilized to detect and type HPV in parallel with in-house PCR tests followed by direct automated sequencing or by sub-cloning and sequencing. The concordance levels along with other tests were evaluated with a Cohen's K value varying between 0.60 to 0.88, indicating good correlation with nearly perfect agreement between hybrid capture II, (HCII) and the linear array test. High sensitivity was recorded by the linear array and HCII with 100% (95% CI, 0.8021 to 1.0000) detection of cervical intraepithelial neoplasia (CIN) III by both methods. Conversely, the PreTect-HPV-Proofer showed high specificity with 12% (95% CI, 0.7966 to 0.9163) positivity on normal samples. The genotyping analysis showed that agreement among tests was only low to moderate with great differences between different HPV types. Multiple infections were detected with poor concordance and sub-cloning assays revealed the presence of a lower number of HPV in comparison to the other methods. In summary, the use of different HPV tests applied to the same group of cervical smears may possibly lead to incongruent results, suggesting the need to standardize type-specific sensitivity of genotyping methods and the need to evaluate their accuracy in detecting multiple HPV infections. This would be a prerequisite for the use of genotyping assays in cervical cancer screening programs.

  7. Considerations related to housing and seismic risk

    Directory of Open Access Journals (Sweden)

    Oana Luca

    2016-06-01

    Full Text Available The paper aims to present the main problems related to the seismic risk and housing in urban settlements in Romania, with special focus on Bucharest, which is the most exposed city. The paper emphasizes the framework related to evolution of technical regulations and seismic safety of residential buildings, highlighting the main dysfunctions in the National Program for Seismic Retrofitting. At the same time, because the collapse of a single residential building may have major negative effects on the surrounding area (buildings, streets, utilities etc., the paper is proposing a methodology for evaluation of damages which may appear in such a case. The article is also suggesting several solutions for improving the design and expertise process and also for the seismic retrofitting of vulnerable buildings, especially housing.

  8. Organellar Genomes from a ∼5,000-Year-Old Archaeological Maize Sample Are Closely Related to NB Genotype

    Science.gov (United States)

    Pérez-Zamorano, Bernardo; Vallebueno-Estrada, Miguel; Martínez González, Javier; García Cook, Angel; Montiel, Rafael; Vielle-Calzada, Jean-Philippe

    2017-01-01

    The story of how preColumbian civilizations developed goes hand-in-hand with the process of plant domestication by Mesoamerican inhabitants. Here, we present the almost complete sequence of a mitochondrial genome and a partial chloroplast genome from an archaeological maize sample collected at the Valley of Tehuacán, México. Accelerator mass spectrometry dated the maize sample to be 5,040–5,300 years before present (95% probability). Phylogenetic analysis of the mitochondrial genome shows that the archaeological sample branches basal to the other Zea mays genomes, as expected. However, this analysis also indicates that fertile genotype NB is closely related to the archaeological maize sample and evolved before cytoplasmic male sterility genotypes (CMS-S, CMS-T, and CMS-C), thus contradicting previous phylogenetic analysis of mitochondrial genomes from maize. We show that maximum-likelihood infers a tree where CMS genotypes branch at the base of the tree when including sites that have a relative fast rate of evolution thus suggesting long-branch attraction. We also show that Bayesian analysis infer a topology where NB and the archaeological maize sample are at the base of the tree even when including faster sites. We therefore suggest that previous trees suffered from long-branch attraction. We also show that the phylogenetic analysis of the ancient chloroplast is congruent with genotype NB to be more closely related to the archaeological maize sample. As shown here, the inclusion of ancient genomes on phylogenetic trees greatly improves our understanding of the domestication process of maize, one of the most important crops worldwide. PMID:28338960

  9. Hereditary Hemochromatosis (HFE genotypes in heart failure: Relation to etiology and prognosis

    Directory of Open Access Journals (Sweden)

    Torp-Pedersen Christian

    2010-07-01

    Full Text Available Abstract Background It is believed that hereditary hemochromatosis (HH might play a role in cardiac disease (heart failure (HF and ischemia. Mutations within several genes are HH-associated, the most common being the HFE gene. In a large cohort of HF patients, we sought to determine the etiological role and the prognostic significance of HFE genotypes. Methods We studied 667 HF patients (72.7% men with depressed systolic function, enrolled in a multicentre trial with a follow-up period of up to 5 years. All were genotyped for the known HFE variants C282Y, H63D and S65C. Results The genotype and allele frequencies in the HF group were similar to the frequencies determined in the general Danish population. In multivariable analysis mortality was not predicted by C282Y-carrier status (HR 1.2, 95% CI: 0.8-1.7; H63D-carrier status (HR 1.0, 95% CI: 0.7-1.3; nor S65C-carrier status (HR 1.2, 95% CI: 0.7-2.0. We identified 27 (4.1% homozygous or compound heterozygous carriers of HFE variants. None of these carriers had a clinical presentation suggesting hemochromatosis, but hemoglobin and ferritin levels were higher than in the rest of the cohort. Furthermore, a trend towards reduced mortality was seen in this group in univariate analyses (HR 0.4, 95% CI: 0.2-0.9, p = 0.03, but not in multivariate (HR 0.5, 95% CI: 0.2-1.2. Conclusion HFE genotypes do not seem to be a significant contributor to the etiology of heart failure in Denmark. HFE variants do not affect mortality in HF.

  10. Hippocampal Sclerosis of Aging, a Common Alzheimer's Disease 'Mimic': Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe.

    Science.gov (United States)

    Nho, Kwangsik; Saykin, Andrew J; Nelson, Peter T

    2016-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer's disease. Four single-nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN, TMEM106B, ABCC9, and KCNMB2 (minor allele frequency for each is >30%). A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (∼50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer's disease contribution to atrophy outside of the hippocampus in older adults.

  11. The rs2071559 AA VEGFR-2 Genotype Frequency Is Significantly Lower in Neovascular Age-Related Macular Degeneration Patients

    Directory of Open Access Journals (Sweden)

    Stefano Lazzeri

    2012-01-01

    Full Text Available In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377 of VEGF-A receptor-2 (VEGFR-2 gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33% in patients with AMD than in the control subjects (34.62%; P=0.0095, chi-square test; Pcorr=0.038; OR=0.42, 95% CI 0.22 to 0.82. In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs.

  12. The rs2071559 AA VEGFR-2 genotype frequency is significantly lower in neovascular age-related macular degeneration patients.

    Science.gov (United States)

    Lazzeri, Stefano; Orlandi, Paola; Figus, Michele; Fioravanti, Anna; Cascio, Elisa; Di Desidero, Teresa; Agosta, Elisa; Canu, Bastianina; Sartini, Maria Sole; Danesi, Romano; Nardi, Marco; Bocci, Guido

    2012-01-01

    In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD) cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377) of VEGF-A receptor-2 (VEGFR-2) gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33%) in patients with AMD than in the control subjects (34.62%; P = 0.0095, chi-square test; P(corr) = 0.038; OR = 0.42, 95% CI 0.22 to 0.82). In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs.

  13. Increased genetic risk or protection for canine autoimmune lymphocytic thyroiditis in Giant Schnauzers depends on DLA class II genotype.

    Science.gov (United States)

    Wilbe, M; Sundberg, K; Hansen, I R; Strandberg, E; Nachreiner, R F; Hedhammar, A; Kennedy, L J; Andersson, G; Björnerfeldt, S

    2010-06-01

    Dogs represent an excellent comparative model for autoimmune thyroiditis as several dog breeds develop canine lymphocytic thyroiditis (CLT), which is clinically similar to Hashimoto's thyroiditis in human. We obtained evidence that dog leukocyte antigen (DLA) class II genotype function as either genetic risk factor that predisposes for CLT or as protective factor against the disease. Genetic diversity at their DLA-DRB1, -DQA1, and -DQB1 loci were defined and potential association to major histocompatibility complex II haplotypes and alleles was analyzed. Giant Schnauzers carrying the DLA-DRB1*01201/DQA1*00101/DQB1*00201 haplotype showed an increased risk (odds ratio of 6.5) for developing CLT. The same risk haplotype has, to date, been observed in three different breeds affected by this disease, Giant Schnauzer, Dobermann, and Labrador Retriever, indicating that it is a common genetic risk factor in a variety of breeds affected by this disease. Importantly, protection for development of the disease was found in dogs carrying the DLA-DRB1*01301/DQA1*00301/DQB1*00501 haplotype (odds ratio of 0.3).

  14. Major histocompatibility complex harbors widespread genotypic variability of non-additive risk of rheumatoid arthritis including epistasis

    Science.gov (United States)

    Wei, Wen-Hua; Bowes, John; Plant, Darren; Viatte, Sebastien; Yarwood, Annie; Massey, Jonathan; Worthington, Jane; Eyre, Stephen

    2016-01-01

    Genotypic variability based genome-wide association studies (vGWASs) can identify potentially interacting loci without prior knowledge of the interacting factors. We report a two-stage approach to make vGWAS applicable to diseases: firstly using a mixed model approach to partition dichotomous phenotypes into additive risk and non-additive environmental residuals on the liability scale and secondly using the Levene’s (Brown-Forsythe) test to assess equality of the residual variances across genotype groups per marker. We found widespread significant (P < 2.5e-05) vGWAS signals within the major histocompatibility complex (MHC) across all three study cohorts of rheumatoid arthritis. We further identified 10 epistatic interactions between the vGWAS signals independent of the MHC additive effects, each with a weak effect but jointly explained 1.9% of phenotypic variance. PTPN22 was also identified in the discovery cohort but replicated in only one independent cohort. Combining the three cohorts boosted power of vGWAS and additionally identified TYK2 and ANKRD55. Both PTPN22 and TYK2 had evidence of interactions reported elsewhere. We conclude that vGWAS can help discover interacting loci for complex diseases but require large samples to find additional signals. PMID:27109064

  15. Diagnostic accuracy of high-risk HPV genotyping in women with high-grade cervical lesions: evidence for improving the cervical cancer screening strategy in China.

    Science.gov (United States)

    Xu, Huihui; Lin, Aifen; Shao, Xiujuan; Shi, Weiwu; Zhang, Yang; Yan, Weihua

    2016-12-13

    Currently, clinical data for primary HPV screening alone are lacking in China. Here, we evaluate cervical cancer screening with primary HPV genotyping, as well as possible future screening strategy. Overall, high-risk HPV (hrHPV) prevalence was 18.2% among hospital-based population in Taizhou area. For cervical intraepithelial neoplasia 2 or worse (CIN2+), the sensitivity of primary hrHPV genotyping strategy and current cervical cancer screening strategy were 93.5%, and 71.1%, respectively; whereas the specificity was 17.5%, and 62.4%, respectively. Current cervical screening strategy had slightly higher positive predictive values (28.4%) for CIN2+ than hrHPV genotyping strategy (21.9%), whereas primary hrHPV genotyping strategy demonstrated higher negative predictive values (94.7%) than current cervical screening strategy (91.1%). Compared to HPV35/39/45/51/56/59/66/68 genotypes, the odds ratios (OR) for CIN2+ in HPV16/18/31/33/52/58 infection women were 3.2 (95% confidence interval [CI] 2.3-4.1). Primary hrHPV genotyping strategy provides a better predictive value than HPV16/18 genotyping alone in guiding the clinical management of the current cervical cancer screening. HPV testing without adjunctive cytology may be sufficiently sensitive for primary cervical cancer screening.

  16. A toolbox for health risk related decisions

    Energy Technology Data Exchange (ETDEWEB)

    Easterly, C.E.; Jones, T.D.

    1996-10-01

    Development efforts since the late 1970s have resulted in a generalized method for ranking health hazards. This method provides the basis for a wide range of applications where decisions are needed for allocating resources on the basis of health risk considerations. It has been used for more than a decade to solve real problems, and it is supported by 23 publications in the open literature. The diversity of this generalized methodology allows us to provide support in a great number of problem areas. we give four examples in this manuscript: the relative toxicities of petroleum mixtures; a method to derive Emergency Response Planning Guides; an estimate of the possible carcinogenic potency of tungsten, an alternative material to depleted uranium for heavy armor penetrators; and an approach to low dose extrapolation. Our experience suggests that many more applications of the original concept and variations on it can be of utility in military situations. Some potentially fruitful areas may be in the: development of a health-risk-ranking system for alternative solutions to manufacturing, waste management, and remediation; provision of a basis for identifying levels of hazardous agents which are below health concerns, or which should be of concern; development of a framework for evaluating chemicals and radioactive materials on the same basis, and in the development of a battery of in vitro bioassays which could take the place of long-term whole animal tests.

  17. Climate Change and Food-Related Risks

    Directory of Open Access Journals (Sweden)

    Isidro Juan Mirón Pérez

    2017-06-01

    Full Text Available There are two principal concepts to take into account relating food and climate change: food security and food safety. Most papers linking climate change to food risks deal with the first one: the security of the food supply.The increase of the concentration of carbon dioxide in the atmosphere, together with the rise of the temperatures on a global level would theorically lead to greater yields of crops grown for human and animal consumption. Howevwe, most of these studies have shown that, in general, crop yields are decreasing as this global change also brings about an increase in the frequency of extreme weather events. In adition, these weather anomalies would be unevenly spread and affect developing countries, which are less capable of tackling this change, more severely. All these factors would result in greater uncertainty in the supply of food, which consequently would be less predictable and leave it more exposed to market speculation.A rise in average temperatures would be expected to increase the risk of proliferation of foodborne disease-causing microorganisms such as Salmonella or Campylobacter. Nevertheless, a trend of this sort has not been detected yet in developed countries, where information systems allow the temporal evolution of the occurrence of those diseases to be tracked, since means for food preservation and food controls are wide spread.

  18. Naturally occurring precore/core region mutations of hepatitis B virus genotype C related to hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Dong-Won Kim

    Full Text Available Previous studies have proved the presence of several distinct types of mutations in hepatitis B virus (HBV infections, which are related to the progression of liver disease. However, few reports have detailed the mutation frequencies and mutation patterns in the precore/core (preC/C region, which are based on the clinical status and HBeAg serostatus. Our aim in this study is to investigate the relationships between the preC/C mutations and clinical severity or HBeAg serostatus from patients chronically infected with HBV genotype C. A total of 70 Korean chronic patients, including 35 with hepatocellular carcinoma (HCC, participated in this study. HBV genotyping and precore/core mutations were analyzed by direct sequencing. All patients were confirmed to have genotype C infections. Mutations in the C region were distributed in a non-random manner. In particular, mutations in the MHC class II restricted region were found to be significantly related to HCC. Six (preC-W28*, C-P5H/L/T, C-E83D, C-I97F/L, C-L100I and C-Q182K/* and seven types (preC-W28*, preC-G29D, C-D32N/H, C-E43K, C-P50A/H/Y, C-A131G/N/P and C-S181H/P of mutations in the preC/C region were found to be related to HCC and to affect the HBeAg serostatus, respectively. In conclusion, our data indicated that HBV variants in the C region, particularly in the MHC class II restricted region, may contribute to the progress of HCC in chronic patients infected with genotype C. In addition, we found several distinct preC/C mutations in the Korean chronic cohort, which affect the clinical status of HCC and HBeAg serostatus of patients infected with genotype C.

  19. Cathecol-O-methyl transferase Val158Met genotype is not a risk factor for conversion disorder.

    Science.gov (United States)

    Armagan, E; Almacıoglu, M L; Yakut, T; Köse, A; Karkucak, M; Köksal, O; Görükmez, O

    2013-03-19

    Alterations in catechol-O-methyltransferase (COMT) activity are involved in various types of neurological disorders. We examined a possible association between the COMT Val158Met polymorphism and conversion disorder in a study of 48 patients with conversion disorder and 48 control patients. In the conversion disorder group, 31 patients were Val/Met heterozygotes, 15 patients were Val/Val homozygotes and 2 patients were Met/Met homozygotes. In the control group, 32 patients were Val/Met heterozygotes and 16 patients were Val/Val homozygotes. There was no significant difference between the groups. We conclude that the COMT Val158Met genotype is quite common in Turkey and that it is not a risk factor for conversion disorder in the Turkish population.

  20. Joint Effect of Genotypic and Phenotypic Features of Reproductive Factors on Endometrial Cancer Risk

    OpenAIRE

    Zhanwei Wang; Harvey Risch; Lingeng Lu; Irwin, Melinda L.; Susan Mayne; Peter Schwartz; Thomas Rutherford; Immaculata De Vivo; Herbert Yu

    2015-01-01

    Prolonged estrogen exposure is believed to be the major cause of endometrial cancer. As possible markers of estrogen exposure, various menstrual and reproductive features, e.g., ages at menarche and menopause, are found to be associated with endometrial cancer risk. In order to assess their combined effects on endometrial cancer, we created the total number of menstrual cycles (TNMC) that a woman experienced during her life or up to the time of study and two genetic risk scores, GRS1 for age ...

  1. Cystatin C and Risk of Diabetes and the Metabolic Syndrome - Biomarker and Genotype Association Analyses.

    Directory of Open Access Journals (Sweden)

    Martin Magnusson

    .478, respectively.We were able to replicate our previously shown association between high levels of cystatin C and increased risk of future development of MetS. However, a causal involvement of cystatin C in the etiology of MetS or diabetes seems unlikely since genetic elevation of plasma cystatin C was not significantly related to incidence of these diseases.

  2. Morphological and sequence-related amplified polymorphism-based molecular diversity of local and exotic wheat genotypes.

    Science.gov (United States)

    Abdelkhalik, S M; Salem, A K M; Abdelaziz, A R; Ammar, M H

    2016-04-28

    Assessing genetic diversity is a prerequisite for the genetic improvement of wheat. Molecular markers offer accurate and reproducible means for assessing genetic diversity. Field performance and sequence-related amplified polymorphism (SRAP)-based assessment of molecular diversity was carried out on a set of 10 local and introduced bread wheat (Triticum sativum L.) genotypes grown in the middle arid region of Saudi Arabia. The results revealed highly significant differences among the studied phenological traits and revealed a significant amount of genetic diversity across the tested genotypes. The overall performance revealed the superiority of KSU 102 in terms of yield and its components, with a yield potential of 8.7 tons/ha. Highly significant and positive correlations were observed among grain yield and biological yield, and also, spike length and spike weight. Thirteen SRAP primer combinations successfully amplified 954 fragments. The total number of genetic loci analyzed was 312. The overall polymorphism ratio was 99.67%, ranging from 98 to 100%. The polymorphic information content values ranged from 0.67 for ME11 x EM5 to 0.97 for ME9 x EM4 and ME11 x EM6, respectively. The wheat genotypes were clustered based on their genetic constitution and origin. The results demonstrate the power of SRAP primers for detecting molecular diversity and for varietal discrimination. The results show that high levels of genetic diversity exist, and suggest the potential of the tested materials for wheat crop improvement in the arid central region of Saudi Arabia.

  3. Variation in chilling tolerance for photosynthesis and leaf extension growth among genotypes related to the C-4 grass Miscanthus xgiganteus

    Energy Technology Data Exchange (ETDEWEB)

    Glowacka, K; Adhikari, S; Peng, JH; Gifford, J; Juvik, JA; Long, SP; Sacks, EJ

    2014-09-08

    The goal of this study was to identify cold-tolerant genotypes within two species of Miscanthus related to the exceptionally chilling-tolerant C-4 biomass crop accession: M. xgiganteus 'Illinois' (Mxg) as well as in other Mxg genotypes. The ratio of leaf elongation at 10 degrees C/5 degrees C to that at 25 degrees C/25 degrees C was used to identify initially the 13 most promising Miscanthus genotypes out of 51 studied. Net leaf CO2 uptake (A(sat)) and the maximum operating efficiency of photosystem II (Phi(PSII)) were measured in warm conditions (25 degrees C/20 degrees C), and then during and following a chilling treatment of 10 degrees C/5 degrees C for 11 d. Accessions of M. sacchariflorus (Msa) showed the smallest decline in leaf elongation on transfer to chilling conditions and did not differ significantly from Mxg, indicating greater chilling tolerance than diploid M. sinensis (Msi). Msa also showed the smallest reductions in A(sat) and Phi(PSII), and greater chilling-tolerant photosynthesis than Msi, and three other forms of Mxg, including new triploid accessions and a hexaploid Mxg 'Illinois'. Tetraploid Msa 'PF30153' collected in Gifu Prefecture in Honshu, Japan did not differ significantly from Mxg 'Illinois' in leaf elongation and photosynthesis at low temperature, but was significantly superior to all other forms of Mxg tested. The results suggested that the exceptional chilling tolerance of Mxg 'Illinois' cannot be explained simply by the hybrid vigour of this intraspecific allotriploid. Selection of chilling-tolerant accessions from both of Mxg's parental species, Msi and Msa, would be advisable for breeding new highly chilling-tolerant Mxg genotypes.

  4. Mycorrhizal responsiveness of maize (Zea mays L.) genotypes as related to releasing date and available P content in soil.

    Science.gov (United States)

    Chu, Qun; Wang, Xinxin; Yang, Yang; Chen, Fanjun; Zhang, Fusuo; Feng, Gu

    2013-08-01

    The aim of this study was to compare the mycorrhizal responsiveness among old and recent Chinese maize genotypes (released from 1950s to 2008) in low- and high-Olsen-P soils and to identify parameters that would indicate the relationships between the mycorrhizal responsiveness and the functional traits related to P uptake of maize. A greenhouse factorial experiment was conducted. The factors were maize genotype [Huangmaya (HMY), Zhongdan 2 (ZD2), Nongda 108 (ND108), and NE15], inoculation with or without arbuscular mycorrhizal fungi (AMF) (Rhizophagus irregularis), and Olsen-P levels (4, 9, 18, 36, or 60 mg P kg(-1)). Old and recently released genotypes differed in their response to AMF under low- and high-P supply. Three kinds of responses (in terms of shoot growth) were observed: the response was positive if the soil P content was low, but negative if the soil Olsen-P content was high (HMY and ND108); the response was neutral regardless of soil P content (ZD2); and the response was positive regardless of soil P content (NE15). Principle component (PC) analysis showed that the first PC comprised morphological and physiological traits of maize roots, and the second PC comprised mycorrhizal traits. The opposite was the case, however, in high-P soil. It is concluded that maize breeding selection from 1950s to 2000s is not always against the AM association and that AMF play positive roles in promoting the growth of some maize genotypes in high-P soil. The root length colonization by efficient AMF might be a useful parameter for breeding varieties with increased mycorrhizal responsiveness.

  5. Genotypic and environmental variation in barley limit dextrinase activity and its relation to malt quality

    Institute of Scientific and Technical Information of China (English)

    WANG Xu-dong; YANG Juan; ZHANG Guo-ping

    2006-01-01

    Variation in the limit dextrinase activity of barley malt, and the relationships between limit dextrinase activity and malt quality parameters were investigated using eight cultivars grown at seven diverse locations in China for two successive years.Limit dextrinase activity varied with genotype and location, with the levels ranging from 0.245 U/g to 0.980 U/g. The results showed that the variation in limit dextrinase activity was more attributable to the environment (location and year) than to the genotype. The response of limit dextrinase activity to the environment differed markedly among cultivars, and was reflected by large difference in coefficient of variation of cultivars across diverse locations. Regression analysis showed that limit dextrinase activity was negatively correlated with malt viscosity (r=-0.52, P<0.01), positively correlated with Kolbach index (r=0.38,P<0.01) and malt extract (r=0.30, P<0.05), but had no significant correlation with malt protein content and diastatic power.

  6. Energy balance, insulin-related genes and risk of colon and rectal cancer.

    Science.gov (United States)

    Slattery, Martha L; Murtaugh, Maureen; Caan, Bette; Ma, Khe Ni; Neuhausen, Susan; Samowitz, Wade

    2005-05-20

    Energy balance, or the ability to maintain body weight by balancing energy intake with energy expenditure, appears to be important in the etiology of colon cancer. One possible mechanism whereby energy balance may be associated with colorectal cancer is through its association with insulin. In our study, we evaluate the interaction between polymorphisms in 4 genes thought to be involved in insulin-related functions and components of energy balance with risk of colorectal cancer. Data from 2 population-based case-control studies of colon and rectal cancer conducted in Utah and Northern California were used to evaluate associations between body mass index (BMI), physical activity, energy intake and sucrose-to-fiber ratio and a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide -202 of the IGFBP3, the G972R polymorphism of the IRS1 gene and the G1057D polymorphism of the IRS2 gene. A total of 1,346 incident colon cancer cases and 1,544 population-based controls and 952 incident rectal cancer cases and 1,205 controls were available for analysis. Inconsistent associations were identified between BMI, physical activity, energy intake and insulin-related genes. The 192/192 IGF1 genotype was associated with significant reduction in colon cancer risk among those with high physical activity (odds ratio [OR] 0.57; 95% confidence interval [CI] 0.39-0.83; p interaction 0.01). Although there was no significant pattern of interaction between either BMI or energy intake and polymorphisms assessed, specific sources of energy did appear to be more related to colon cancer risk in the presence of specific IRS2 and IGF1 genotypes. A high sucrose-to-fiber ratio increased risk of colon cancer in men who had the IRS2 DD genotype and among men who did not have the 192/192 IGF1 genotype. In summary, these data support the importance of components of energy balance in risk of colorectal cancer. Obesity, physical activity and energy intake appear to alter risk of

  7. [Prevalence of non-vaccinable high risk genotypes of human papillomavirus in the Early Detection of Cervical Cancer Program in Cantabria].

    Science.gov (United States)

    Paz-Zulueta, María; Fernández-Feito, Ana; Amparán Ruiz, Marina; Azofra Olave, Asunción; Martín Seco, Yolanda; Ojugas Zabala, Sonia; Otero García, Aurora; Royano Rasines, Carmen; Sarabia-Lavín, Raquel; Torres Manrique, Blanca; Santibáñez Margüello, Miguel

    2016-01-01

    To estimate the prevalence of infection with non-vaccinable high risk genotypes of human papillomavirus (HPV). Cross-sectional study. Seven randomly selected health centres in Cantabria (Northern Spain). All women with an evaluable vaginal smear (n=3,359) between 2010 and 2011. The variables collected were cytological diagnosis, PCR results, and family planning method. The vaginal smear results were classified with the Bethesda system. The classification by Muñoz et al. was used for typing as oncogenic risk HPV. Proportions and odds ratio (OR) were estimated with corresponding confidence intervals at 95% (95% CI). The prevalence of HPV infection was 2.71% (95% CI: 2.15 to 3.27). The prevalence of high oncogenic risk HPV genotypes was 2.26%; (95% CI: 1.75 to 2.78). The most frequent genotype was 16 (28.89%). More than half of the women were positive for one of the non-vaccinable high risk genotypes: 51 (18.89%) and 58 (13.33%) and 68 (12.22%) or 31 (11.11%). At least two non-vaccinable high-risk genotypes co-existed in 23.33% of women. Younger women (≤30 years) had twice the risk of any HPV infection: OR 2.01 (95% CI: 1.02 to 3.96); and were twice as likely to use condoms compared to hormonal contraceptives, OR 2.09 (95% CI: 1.64 to 2.67). According to the high percentage of non-vaccinable high oncogenic risk HPV types, there should be a re-think of the prevention strategy in the population, who may have a false sense of protection. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  8. The assessment of risk factors for the Central/East African Genotype of chikungunya virus infections in the state of Kelantan: a case control study in Malaysia.

    Science.gov (United States)

    Yusoff, Ahmad Faudzi; Mustafa, Amal Nasir; Husaain, Hani Mat; Hamzah, Wan Mansor; Yusof, Apandi Mohd; Harun, Rozilawati; Abdullah, Faezah Noor

    2013-05-08

    The aims of the study were to assess the risk factors in relation to cross border activities, exposure to mosquito bite and preventive measures taken.An outbreak of chikungunya virus (CHIKV) infection in Malaysia has been reported in Klang, Selangor (1998) and Bagan Panchor, Perak (2006). In 2009, CHIKV infection re-emerged in some states in Malaysia. It raises the possibilities that re-emergence is part of the epidemics in neighbouring countries or the disease is endemic in Malaysia. For this reason, A community-based case control study was carried out in the state of Kelantan. Prospective case finding was performed from June to December 2009. Those who presented with signs and symptoms of CHIKV infection were investigated. We designed a case control study to assess the risk factors. Assessment consisted of answering questions, undergoing a medical examination, and being tested for the presence of IgM antibodies to CHIKV. Descriptive epidemiological studies were conducted by reviewing both the national surveillance and laboratory data. Multivariable logistic regression analysis was performed to determine risk factors contributing to the illness. Cases were determined by positive to RT-PCR or serological for antibodies by IgM. CHIKV specificity was confirmed by DNA sequencing. There were 129 suspected cases and 176 controls. Among suspected cases, 54.4% were diagnosed to have CHIKV infection. Among the controls, 30.1% were found to be positive to serology for antibodies [IgM, 14.2% and IgG, 15.9%]. For analytic study and based on laboratory case definition, 95 were considered as cases and 123 as controls. Those who were positive to IgG were excluded. CHIKV infection affected all ages and mostly between 50-59 years old. Staying together in the same house with infected patients and working as rubber tappers were at a higher risk of infection. The usage of Mosquito coil insecticide had shown to be a significant protective factor. Most cases were treated as outpatient

  9. Glycan Specificity of P[19] Rotavirus and Comparison with Those of Related P Genotypes

    Science.gov (United States)

    Liu, Yang; Ramelot, Theresa A.; Huang, Pengwei; Liu, Yan; Li, Zhen; Feizi, Ten; Zhong, Weiming; Wu, Fang-Tzy; Tan, Ming; Kennedy, Michael A.

    2016-01-01

    ABSTRACT The P[19] genotype belongs to the P[II] genogroup of group A rotaviruses (RVs). However, unlike the other P[II] RVs, which mainly infect humans, P[19] RVs commonly infect animals (pigs), making P[19] unique for the study of RV diversity and host ranges. Through in vitro binding assays and saturation transfer difference (STD) nuclear magnetic resonance (NMR), we found that P[19] could bind mucin cores 2, 4, and 6, as well as type 1 histo-blood group antigens (HBGAs). The common sequences of these glycans serve as minimal binding units, while additional residues, such as the A, B, H, and Lewis epitopes of the type 1 HBGAs, can further define the binding outcomes and therefore likely the host ranges for P[19] RVs. This complex binding property of P[19] is shared with the other three P[II] RVs (P[4], P[6], and P[8]) in that all of them recognized the type 1 HBGA precursor, although P[4] and P[8], but not P[6], also bind to mucin cores. Moreover, while essential for P[4] and P[8] binding, the addition of the Lewis epitope blocked P[6] and P[19] binding to type 1 HBGAs. Chemical-shift NMR of P[19] VP8* identified a ligand binding interface that has shifted away from the known RV P-genotype binding sites but is conserved among all P[II] RVs and two P[I] RVs (P[10] and P[12]), suggesting an evolutionary connection among these human and animal RVs. Taken together, these data are important for hypotheses on potential mechanisms for RV diversity, host ranges, and cross-species transmission. IMPORTANCE In this study, we found that our P[19] strain and other P[II] RVs recognize mucin cores and the type 1 HBGA precursors as the minimal functional units and that additional saccharides adjacent to these units can alter binding outcomes and thereby possibly host ranges. These data may help to explain why some P[II] RVs, such as P[6] and P[19], commonly infect animals but rarely humans, while others, such as the P[4] and P[8] RVs, mainly infect humans and are predominant

  10. Large-scale genotyping identifies 41 new loci associated with breast cancer risk

    DEFF Research Database (Denmark)

    Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna

    2013-01-01

    Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10...

  11. Microsomal epoxide hydrolase genotypes and the risk for head and neck cancer.

    NARCIS (Netherlands)

    Lacko, M.; Roelofs, H.M.J.; Morsche, R.H.M. te; Voogd, A.C.; Ophuis, MB Oude; Peters, W.H.M.; Manni, J.J.

    2008-01-01

    BACKGROUND: Microsomal epoxide hydrolase (mEH) is an enzyme involved in the metabolism of (pre)carcinogens in tobacco smoke. We investigated whether functional genetic polymorphisms in mEH may have a risk-modifying effect on head and neck carcinogenesis. METHODS: Blood from 429 patients with oral, p

  12. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk

    DEFF Research Database (Denmark)

    Holmes, Michael V; Newcombe, Paul; Hubacek, Jaroslav A;

    2011-01-01

    The MTHFR 677C→T polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias wa...

  13. The presence of PAI-1 4G/5G and ACE DD genotypes increases the risk of early-stage AVF thrombosis in hemodialysis patients.

    Science.gov (United States)

    Güngör, Yahya; Kayataş, Mansur; Yıldız, Gürsel; Özdemir, Öztürk; Candan, Ferhan

    2011-01-01

    In this study, we investigated the relationship between early arteriovenous fistula (AVF) thrombosis with angiotensin-converting enzyme (ACE) gene and thrombophilic factor gene polymorphisms. Thirty-five patients who suffered from three or more fistula thrombosis episodes in the early period after AVF operation and 33 control patients with no history of thrombosis for at least 3 years were enrolled in this study. Factor V G1691A Leiden, factor V H1299R (R2), prothrombin G20210A, factor XIIIV34L, β-fibrinogen-455 G-A, glycoprotein IIIa L33P human platelet antigens (HPA-1), methylenetetrahydrofolate reductase C677T, and methylenetetrahydrofolate reductase A1298C gene polymorphisms were similar in both groups (p > 0.05). Plasminogen activator inhibitor 1 (PAI-1) 4G/5G genotype in the study group and 4G/4G genotype in the control group were significantly higher (p = 0.014). No significant difference was detected in terms of the 5G/5G genotype. With regard to the ACE gene polymorphism, the control group showed more ID genotype (19/33, 57.6%), whereas the study group showed more DD genotype (17/35, 48.6%). II genotype was similar in both groups (x(2) = 7.40, p = 0.025). The rate of ACE inhibitor-angiotensin II receptor blockers use was 5/35 in the study group (14.3%) and 5/33 in the control group (15.2%). Individuals with PAI-1 4G/5G genotype showed 5.03 times more risk of thrombosis when compared with 4G/4G and 5G/5G genotypes [p = 0.008, OR = 5.03, 95% confidence interval (1.44:17.64)]. Individuals with ACE DD genotype showed 4.25 times more risk of thrombosis when compared with II and ID [p = 0.008, OR = 4.25, 95% confidence interval (1.404:12.83)]. PAI-1 4G/5G and ACE DD genotypes are associated with increased risk for early AVF thrombosis.

  14. Relation between CYP2C19 phenotype and genotype in a group of Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Rafael Linden

    2009-09-01

    Full Text Available The CYP2C19 gene presents polymorphism affecting the pharmacokinetics of several drugs of clinical importance. The purpose of this study was to investigate the correlation between CYP2C19 genotype and metabolic phenotype in a group of 38 Brazilian volunteers, evaluating the phenotype prediction capacity of the genotyping procedure. For CYP2C19 phenotyping, omeprazole was used as the probe drug, using the hydroxylation metabolic ratio as the phenotypic indicator. Venous blood samples were drawn before and three hours after an oral administration of 20 mg omeprazole. The plasma concentrations of omeprazole and hydroxy-omeprazole were determined by high performance liquid chromatography. The genotyping assay was carried out using a Real-Time-PCR-based assay, identifying the alleles *1 (completely functional, *2, *3 and *4 (null. The phenotyping procedure estimated the presence of 4 poor, 34 extensive and 1 ultra-extensive metabolizer. The genotyping identified 4 poor, 23 extensive and 11 intensive metabolizers. The groups of volunteers classified according to the number of active alleles of CYP2C19 had significant differences in the metabolic ratios of omeprazole hydroxylation. However, volunteers exhibiting the same number of active alleles presented different phenotypes. Therefore, the phenotyping of CYP2C19 is a more promising alternative to dose individualization of CYP2C19 substrate drugs.O gene CYP2C19 apresenta polimorfismo genético, com impacto importante na farmacocinética de diversos fármacos de importância clínica. O objetivo deste estudo foi avaliar a correlação entre genótipo e fenótipo de CYP2C19 em um grupo de 38 voluntários brasileiros, avaliando a capacidade de predição do fenótipo a partir de testes de genotipagem. Para a fenotipagem, utilizou-se omeprazol (OME como fármaco-sonda para CYP2C19, empregando sua razão metabólica de hidroxilação como indicador fenotípico. Amostras de sangue foram coletadas antes e tr

  15. The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil.

    Science.gov (United States)

    Lopes, Carmen Andréa F; Soares, Marcelo A; Falci, Diego R; Sprinz, Eduardo

    2015-01-01

    HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1%) and K130N (40.6%). Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%). There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option.

  16. The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil

    Directory of Open Access Journals (Sweden)

    Carmen Andréa F. Lopes

    2015-01-01

    Full Text Available HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1% and K130N (40.6%. Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%. There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option.

  17. Naturally occurring mutations in large surface genes related to occult infection of hepatitis B virus genotype C.

    Directory of Open Access Journals (Sweden)

    Hong Kim

    Full Text Available Molecular mechanisms related to occult hepatitis B virus (HBV infection, particularly those based on genotype C infection, have rarely been determined thus far in the ongoing efforts to determine infection mechanisms. Therefore, we aim to elucidate the mutation patterns in the surface open reading frame (S ORF underlying occult infections of HBV genotype C in the present study. Nested PCRs were applied to 624 HBV surface antigen (HBsAg negative Korean subjects. Cloning and sequencing of the S ORF gene was applied to 41 occult cases and 40 control chronic carriers. Forty-one (6.6% of the 624 Korean adults with HBsAg-negative serostatus were found to be positive for DNA according to nested PCR tests. Mutation frequencies in the three regions labeled here as preS1, preS2, and S were significantly higher in the occult subjects compared to the carriers in all cases. A total of two types of deletions, preS1 deletions in the start codon and preS2 deletions as well as nine types of point mutations were significantly implicated in the occult infection cases. Mutations within the "a" determinant region in HBsAg were found more frequently in the occult subjects than in the carriers. Mutations leading to premature termination of S ORF were found in 16 occult subjects (39.0% but only in one subject from among the carriers (2.5%. In conclusion, our data suggest that preS deletions, the premature termination of S ORF, and "a" determinant mutations are associated with occult infections of HBV genotype C among a HBsAg-negative population. The novel mutation patterns related to occult infection introduced in the present study can help to broaden our understanding of HBV occult infections.

  18. Combined UGT1A1 and UGT1A6 genotypes together with a stressful life event increase breast cancer risk

    OpenAIRE

    2010-01-01

    Combined UGT1A1 and UGT1A6 genotypes together with a stressful life event increase breast cancer risk phone: +49-711-81015765 (Justenhoven, Christina) (Justenhoven, Christina) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University Tuebingen - Auerbachstrasse 112 - 70376 - Stuttgart - GERMANY (Justenhoven, Christina) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University Tuebingen - Auerbachstrasse 11...

  19. Managing IT-related operational risks

    Directory of Open Access Journals (Sweden)

    Savić Ana

    2008-01-01

    Full Text Available Not so long ago, information technology (IT risk occupied a small corner of operational risk - the opportunity loss from a missed IT development deadline. Today, the success of an entire financial institution may lay on managing a broad landscape of IT risks. IT risk is a potential damage to an organization's value, resulting from inadequate managing of processes and technologies. IT risk includes the failure to respond to security and privacy requirements, as well as many other issues such as: human error, internal fraud through software manipulation, external fraud by intruders, obsolesce in applications and machines, reliability issues or mismanagement. The World Economic Forum provides best information about this problem. They rank a breakdown of critical information infrastructure among the most likely core global risks, with 10-20 % likelihood over the next 10 years and potential worldwide impact of $250 billion. Sustained investment in IT - almost $1.2 trillion or 29% of 2006 private-sector capital investment in the U.S. alone fuels growing exposure to IT risk. Greg Hughes, chief strategy officer in Symantec Corp. recently claimed "IT risk management is more than using technology to solve security problems. With proper planning and broad support, it can give an organization the confidence to innovate, using IT to outdistance competitors".

  20. Prevalence of High-Risk Human Papillomavirus (HR-HPV) Genotypes and Multiple Infections in Cervical Abnormalities from Northern Xinjiang, China.

    Science.gov (United States)

    Wang, Lina; Wang, Pengyan; Ren, Yan; Du, Jingyun; Jiang, Jianjun; Jia, Xuesong; Chen, Chuangfu; Wang, Yuanzhi

    2016-01-01

    Multiple human papillomavirus (HPV) genotypes often coexist within the cervical epithelia and are frequently detected together in various grades of the cervical neoplasia. To date, only a few reports exist on multiple HPV infections of HPV in Xinjiang Uygur Autonomous Region (XUAR). In the present study, we investigated the prevalence of High-Risk HPV (HR-HPV) genotypes and multiple infections. Cervical cytology samples were collected from 428 women who presented cervical abnormalities. Genotyping of HPV was performed by polymerase chain reaction-sequencing based typing (PCR-SBT) using consensus primers and specific primers. Of them, 166 samples were positive for HPV according to PCR results using the consensus primers. These samples contained cervical abnormalities enriched with inflammation (n = 107), cervical intraepithelial neoplasia (CIN) I (n = 19), CINII-III (n = 9) and cervical cancer (n = 31). Of the 166 HPV positive samples as determined by PCR analysis, 151 were further typed by PCR-SBT using 19 pairs of genotype-specific primers. Using this method, 17 different HR-HPV genotypes were identified. The most frequently observed HPV genotypes were HPV16 (44.0%, 73/166), 53 (28.9%, 48/166), 52 (25.3%, 42/166), 58 (22.3%, 37/166) and 35 (17.5%, 29/166). The proportions of single and multiple infections in the HPV-positive specimens were 34.9% and 65.1%, respectively. Multiple HPV types were most prevalent in the inflammatory state (63.0%), followed by cervical cancer (24.1%), CINI (11.1%), and CINII-III (1.9%). The results of our data analyses suggested that i) multiple HPV infection is not necessarily correlated with the severity of cervical abnormalities; and ii) among the multiple HPV infections, double infections combined with HPV16 is the most common. In addition, L1 full-length sequences of the top five high-risk HPV genotypes were amplified and sequenced. According to the L1 sequence of the epidemic genotypes that were amplified, we found that these

  1. Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype.

    Science.gov (United States)

    Malfatti, Edoardo; Lehtokari, Vilma-Lotta; Böhm, Johann; De Winter, Josine M; Schäffer, Ursula; Estournet, Brigitte; Quijano-Roy, Susana; Monges, Soledad; Lubieniecki, Fabiana; Bellance, Remi; Viou, Mai Thao; Madelaine, Angéline; Wu, Bin; Taratuto, Ana Lía; Eymard, Bruno; Pelin, Katarina; Fardeau, Michel; Ottenheijm, Coen A C; Wallgren-Pettersson, Carina; Laporte, Jocelyn; Romero, Norma B

    2014-04-12

    Nemaline myopathy (NM) is a rare congenital myopathy characterised by hypotonia, muscle weakness, and often skeletal muscle deformities with the presence of nemaline bodies (rods) in the muscle biopsy. The nebulin (NEB) gene is the most commonly mutated and is thought to account for approximately 50% of genetically diagnosed cases of NM. We undertook a detailed muscle morphological analysis of 14 NEB-mutated NM patients with different clinical forms to define muscle pathological patterns and correlate them with clinical course and genotype. Three groups were identified according to clinical severity. Group 1 (n = 5) comprises severe/lethal NM and biopsy in the first days of life. Group 2 (n = 4) includes intermediate NM and biopsy in infancy. Group 3 (n = 5) comprises typical/mild NM and biopsy in childhood or early adult life. Biopsies underwent histoenzymological, immunohistochemical and ultrastructural analysis. Fibre type distribution patterns, rod characteristics, distribution and localization were investigated. Contractile performance was studied in muscle fibre preparations isolated from seven muscle biopsies from each of the three groups. G1 showed significant myofibrillar dissociation and smallness with scattered globular rods in one third of fibres; there was no type 1 predominance. G2 presented milder sarcomeric dissociation, dispersed or clustered nemaline bodies, and type 1 predominance/uniformity. In contrast, G3 had well-delimited clusters of subsarcolemmal elongated rods and type 1 uniformity without sarcomeric alterations. In accordance with the clinical and morphological data, functional studies revealed markedly low forces in muscle bundles from G1 and a better contractile performance in muscle bundles from biopsies of patients from G2, and G3.In conclusion NEB-mutated NM patients present a wide spectrum of morphological features. It is difficult to establish firm genotype phenotype correlation. Interestingly, there was a correlation

  2. The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis.

    Directory of Open Access Journals (Sweden)

    Hans Dieter Nischalke

    Full Text Available BACKGROUND: An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409 has recently been identified as a susceptibility factor for liver damage in steatohepatitis. Here, we studied whether the PNPLA3 rs738409 polymorphism also affects predisposition to hepatocellular carcinoma (HCC. METHODS: We compared distributions of PNPLA3 genotypes in 80 and 81 Caucasian patients with alcoholic and hepatitis C virus (HCV-associated HCC to 80 and 81 age- and sex-matched patients with alcohol-related and HCV-related cirrhosis without HCC, respectively. PNPLA3 genotypes in 190 healthy individuals from the same population served as reference. Potential confounders obesity, diabetes, HCV genotype and HBV co-infection were controlled by univariate and multivariate logistic regression with forward variable selection. RESULTS: PNPLA3 genotypes were in Hardy-Weinberg equilibrium for all study groups. The frequency of the 148M allele was significantly (p<0.001 increased in alcoholic cirrhosis with (53.7% and without HCC (36.2% but was not different between healthy controls (22.9% and patients with cirrhosis (25.3%; p = 0.545 and HCC (30.2%; p = 0.071 due to hepatitis C. HCC risk was highest in 148M/M homozygous patients with alcoholic liver disease (odds ratio (OR 16.8 versus healthy controls; 95% confidence interval (CI 6.68-42.43, p<0.001. Finally, multivariate regression confirmed 148M/M homozygosity (OR 2.8; 95%-CI: 1.24-6.42; p = 0.013 as HCC risk factor in alcoholic cirrhosis. In HCV-related cirrhosis only HCV genotype 1 was confirmed as a HCC risk factor (OR 4.2; 95%-CI: 1.50-11.52; p = 0.006. CONCLUSION: The PNPLA3 148M variant is a prominent risk factor for HCC in patients with alcoholic cirrhosis, while its effects are negligible in patients with cirrhosis due to HCV. This polymorphism provides an useful tool to identify individuals with particularly high HCC risk in patients with alcoholic liver disease that

  3. Th1/Th2 cytokines and their genotypes as predictors ofhepatitis B virus related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC), the predominant typeof primary liver cancer, is one of the most serious lifethreateningmalignancies, worldwide. In majority ofthe cases, HCC develops after prolonged and persistentchronic liver disease. hepatitis B virus (HBV) or HCVinfection is prominent etiological factors, attributing to this condition. It has been well documented that HBV,being the inducer of chronic inflammation, is the maincausative agent in causing HCC, particularly in Asiancountries. The HBV infection leads to a wide range ofclinical symptoms from carrier state to malignancy.Cytokines being immune-modulatory molecules, arethe key mediators in the defense mechanism againstviral infection. In this regard, this review will detail thesubstantial role of key Th1: interleukin 1 (IL-1), IL-2,IL-12, tumor necrosis factor-α, interferon-γ; Th2: IL-4,IL-10 and non Th1/Th2: IL-6, transforming growthfactor-β1 cytokines genotypes in analyzing the variabilityin the clinical manifestations in an HBV-afflicted individual,which might finally, culminates into HCC. Since cytokineproduction is regulated genetically, the cytokine promoterregion single-nucleotide polymorphisms induced changes,greatly affects the cytokine production, thus resulting intodifferential outcome of immune balance.

  4. Amylolytic activity and carbohydrate levels in relation to coleoptile anoxic elongation in Oryza sativa genotypes.

    Science.gov (United States)

    Pompeiano, Antonio; Fanucchi, Francesca; Guglielminetti, Lorenzo

    2013-11-01

    Among starchy seeds, rice has the unique capacity to germinate successfully under complete anaerobiosis. In this conditions, starch degradation is supported by a complete set of starch-degrading enzymes that are absent or inactive in cereals except rice. A characterization of carbohydrate metabolism and starch-degrading enzyme activity across twenty-nine genotypes of Oryza sativa L. is presented here. The zymogram of amylolytic activities present in rice embryos and endosperms under anaerobic conditions seven days after sowing (DAS) revealed marked differences among cultivars. Coleoptile elongation was positively correlated with total amylolytic activities and α-amylase activity in embryos, and negatively correlated with α-amylase activity in endosperm. Moreover, carbohydrate content in embryos was found to be positively correlated with total amylolytic activities under anaerobic conditions, while a negative relationship was recorded in the endosperm. Carbohydrate status in rice seedlings has a primary importance in sustaining coleoptile elongation towards the surface. The relationship between carbohydrate level in embryo and anoxic germination, as well as with total amylolytic activities present in rice embryo under anaerobic condition 7 DAS, is consistent with the role of sugar metabolism to support rice germination under oxygen-deprived environment.

  5. Effect of Denture-Related Stomatitis Fluconazole Treatment on Oral Candida albicans Susceptibility Profile and Genotypic Variability.

    Science.gov (United States)

    Figueiral, Maria Helena; Fonseca, Patrícia; Lopes, Maria Manuel; Pinto, Eugénia; Pereira-Leite, Teresa; Sampaio-Maia, Benedita

    2015-01-01

    Denture-related stomatitis (DRS) is the most common condition affecting removable-denture wearers, and Candida albicans the most frequent pathogenic agent. Systemic antifungal treatment is indicated but recurrences are frequent. The aim of this study was to characterize the oral load, fluconazole susceptibility profile and genotypic variability of oral C. albicans isolates from patients with DRS before (T0), immediately after fluconazole treatment (Tat) and after 6-months follow-up (T6m). Eighteen patients presenting DRS and treated with fluconazole were followed at the Faculty of Dentistry of Oporto University. Seventy C. albicans isolates were obtained and identified using standard cultural and biochemical multi-testing. Fluconazole susceptibility was tested by E-test(®). Microsatellite-primed PCR was performed to assess the genotypic variability of C. albicans isolates. The patients' mean age was 58.0±3.2 years, and 55.6%/44.4% had total/partial dentures. Before treatment, 22.2%, 44.4% and 33.3% of the patients presented DRS type I, II or III, respectively. Fluconazole treatment healed or improved DRS in 77.8% of the patients, accompanied by an 83.5% reduction in oral C. albicans load. However, after 6-months, oral C. albicans load increased significantly and DRS severity was similar to the one observed before treatment. Moreover, the prevalence of patients presenting fluconazole resistant isolates of C. albicans increased significantly throughout the study: T0-5.6%, Tat-10.0% and T6m-42.9%. A change in the genotypic variability of C. albicans isolates was also verified, being mostly associated to fluconazole susceptibility profile change. In conclusion, fluconazole presents a good short-term DRS treatment efficiency, but may be associated to a long-term emergence of C. albicans fluconazole resistance.

  6. Prevalence, Genotype Distribution and Risk Factors for Cervical Human Papillomavirus Infection in the Grand Tunis Region, Tunisia.

    Science.gov (United States)

    Ardhaoui, Monia; Ennaifer, Emna; Letaief, Hajer; Salsabil, Rejaibi; Lassili, Thalja; Chahed, Karim; Bougatef, Souha; Bahrini, Asma; El Fehri, Emna; Ouerhani, Kaouther; Paez Jimenez, Adela; Guizani, Ikram; Boubaker, Med Samir; Ben Alaya, Nissaf Bouafif Ép

    2016-01-01

    Implementation of Human Papillomavirus (HPV) vaccination should be considered a key cervical cancer prevention strategy in Tunisia, where Pap smear screening is not efficient. This study aims to estimate the prevalence and to identify risk factors associated with HPV infection among women from Grand Tunis, Tunisia. We conducted a cross-sectional study, between December 2012 and May 2013. Eligible women for this study were those aged 18-65 years, sexually active, who sought medical attention at their primary health care centre or clinic in Grand Tunis, Tunisia and who gave written consent. A liquid-based Pap smear sample was obtained from all women using a cervical brush. Only women with betaglobin positive test were further analysed for HPV detection and typing. A nested-PCR of the L1 region was performed followed by reverse line blot hybridization to facilitate the specific detection of 31 HPV genotypes. Multiple logistic regression modeling was used for the analysis of associations between variables with some considered possible confounders after checking for interactions. A total of 391 women were enrolled in this study and 325 out of the 391 cervical samples were positive for the betaglobin test. Overall HPV prevalence was 13.2% [9.8%-17.5%], with the following most prevalent HPV genotypes: HPV6 (40%), HPV40 (14%), HPV16 (12%), HPV52 (9%), HPV31 and HPV59 (7%), followed by HPV68 (4%). Mean age of HPV positive women was 40.7±0.92 years. Independently associated risk factors of HPV infection were smoking (OR:2.8 [0.8-9.6]), low income (OR:9.6 [1.4-63.4), bad housing type (OR:2.5 [1-6.8]), partner with multiple sexual relationship (OR:4.5 [0.9-22.9]) and single women (widowed, divorced, separated, never married) (OR:6.9 [1.1-42.2]). This study provides the first national-based estimate of HPV prevalence in Tunisia. Our findings contribute to the evidence on the current burden of HPV infection, the critical role of sexual behaviour and socioeconomic status and

  7. A risk-based microbiological criterion that uses the relative risk as the critical limit

    DEFF Research Database (Denmark)

    Andersen, Jens Kirk; Nørrung, Birgit; da Costa Alves Machado, Simone

    2015-01-01

    criteria. The approach requires the availability of a quantitative microbiological risk assessment model to get risk estimates for food products from sampled food lots. By relating these food lot risk estimates to the mean risk estimate associated to a representative baseline data set, a relative risk......A risk-based microbiological criterion is described, that is based on the relative risk associated to the analytical result of a number of samples taken from a food lot. The acceptable limit is a specific level of risk and not a specific number of microorganisms, as in other microbiological...... estimate can be obtained. This relative risk estimate then can be compared with a critical value, defined by the criterion. This microbiological criterion based on a relative risk limit is particularly useful when quantitative enumeration data are available and when the prevalence of the microorganism...

  8. APOE Genotyping, Cardiovascular Disease

    Science.gov (United States)

    ... Home Visit Global Sites Search Help? APOE Genotyping, Cardiovascular Disease Share this page: Was this page helpful? Also ... of choice to decrease the risk of developing cardiovascular disease (CVD) . However, there is a wide variability in ...

  9. Determinants of sleep disturbances in Rett syndrome: Novel findings in relation to genotype.

    Science.gov (United States)

    Boban, Sharolin; Wong, Kingsley; Epstein, Amy; Anderson, Barbara; Murphy, Nada; Downs, Jenny; Leonard, Helen

    2016-09-01

    Rett syndrome is a rare but severe neurological disorder associated with a mutation in the methyl CpG binding protein 2 (MECP2) gene. Sleep problems and epilepsy are two of many comorbidities associated with this disorder. This study investigated the prevalence and determinants of sleep problems in Rett syndrome using an international sample. Families with a child with a confirmed Rett syndrome diagnosis and a MECP2 mutation registered in the International Rett Syndrome Phenotype Database (InterRett) were invited to participate. Questionnaires were returned by 364/461 (78.9%) either in web-based or paper format. Families completed the Sleep Disturbance Scale for Children and provided information on the presence, nature, and frequency of their child's sleep problems. Multivariate multinomial regression was used to investigate the relationships between selected sleep problems, age group, and genotype and linear regression for the relationships between sleep disturbance scales and a range of covariates. Night waking was the most prevalent sleep problem affecting over 80% with nearly half (48.3%) currently waking often at night. Initiating and maintaining sleep was most disturbed for younger children and those with a p.Arg294* mutation. Severe seizure activity was associated with poor sleep after adjusting for age group, mutation type, and mobility. We were surprised to find associations between the p.Arg294* mutation and some sleep disturbances given that other aspects of its phenotype are milder. These findings highlight the complexities of aberrant MECP2 function in Rett syndrome and explain some of the variation in manifestation of sleep disturbances. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Apolipoprotein E genotype modifies the risk of behavior problems after infant cardiac surgery.

    Science.gov (United States)

    Gaynor, J William; Nord, Alex S; Wernovsky, Gil; Bernbaum, Judy; Solot, Cynthia B; Burnham, Nancy; Zackai, Elaine; Heagerty, Patrick J; Clancy, Robert R; Nicolson, Susan C; Jarvik, Gail P; Gerdes, Marsha

    2009-07-01

    The goal was to evaluate polymorphisms of the APOE gene as modifiers of neurobehavioral outcomes for preschool-aged children with congenital heart defects, after cardiac surgery. A prospective observational study with neurodevelopmental evaluation between the fourth and fifth birthdays was performed. Attention and behavioral skills were assessed through parental report. Parents of 380 children completed the neurobehavioral measures. Child Behavior Checklist scores for the pervasive developmental problem scale were in the at-risk or clinically significant range for 15% of the cohort, compared with 9% for the normative data (P Behavior Checklist indices, including somatic complaints (P = .009), pervasive developmental problems (P = .032), and internalizing problems (P = .009). In each case, the epsilon4 allele was associated with a better outcome. APOE epsilon2 carriers had impaired social skills, compared with epsilon4 carriers (P = .009). For preschool-aged children with congenital heart defects requiring surgery, parental rating scales showed an increased prevalence of restricted behavior patterns, inattention, and impaired social interactions. The APOE epsilon2 allele was associated with increased behavior problems, impaired social interactions, and restricted behavior patterns.

  11. Transcriptional profiles of hybrid Eucalyptus genotypes with contrasting lignin content reveal that monolignol biosynthesis-related genes regulate wood composition

    Directory of Open Access Journals (Sweden)

    Tomotaka eShinya

    2016-04-01

    Full Text Available Eucalyptus species constitutes the most widely planted hardwood trees in temperate and subtropical regions. In this study, we compared the transcript levels of genes involved in lignocellulose formation such as cellulose, hemicellulose and lignin biosynthesis in two selected three-year old hybrid Eucalyptus (Eucalyptus urophylla x E. grandis genotypes (AM063 and AM380 that have different lignin content. AM063 and AM380 had 20.2 and 35.5% of Klason lignin content and 59.0% and 48.2%, -cellulose contents, respectively. We investigated the correlation between wood properties and transcript levels of wood formation-related genes using RNA-seq with total RNAs extracted from developing xylem tissues at a breast height. Transcript levels of cell wall construction genes such as cellulose synthase (CesA and sucrose synthase (SUSY were almost the same in both genotypes. However, AM063 exhibited higher transcript levels of UDP-glucose pyrophosphorylase (UGP and xyloglucan endotransglucoxylase (XTH than those in AM380. Most monolignol biosynthesis- related isozyme genes showed higher transcript levels in AM380. These results indicate monolignol biosynthesis-related genes may regulate wood composition in Eucalyptus. Flavonoids contents were also observed at much higher levels in AM380 as a result of the elevated transcript levels of common phenylpropanoid pathway genes, phenylalanine ammonium lyase (PAL, cinnamate-4-hydroxylase (C4H and 4-coumarate-CoA ligase (4CL. Secondary plant cell wall formation is regulated by many transcription factors. We analyzed genes encoding NAC, WRKY, AP2/ERF and KNOX transcription factors and found higher transcript levels of these genes in AM380. We also observed increased transcription of some MYB and LIM domain transcription factors in AM380 compared to AM063. All these results show that genes related to monolignol biosynthesis may regulate the wood composition and help maintain the ratio of cellulose and lignin contents

  12. Genotype adaptability and stability

    Directory of Open Access Journals (Sweden)

    Dimitrijević Miodrag

    2000-01-01

    Full Text Available One of the primary concerns in breeding programs is a small genotype reaction to environmental factor variation for better usage of yield genetic potential. Particularly if one takes in consideration that yield could van greatly because of more and more variable meteorological conditions. Studies conducted to observe genotype and environmental relations relay on numerous mathematical models, but genotype behavior in various ecological conditions is not, still, precisely defined Major sources of variation influencing genotype behavior in different environments are genotype/environment interaction, genetic background and environmental conditions. These factors could play an important role in establishing growth regions for maximal realization of genotype genetic potential, as well as in selection of genotypes having better response to complex requirements of particular growth region. Stability, the genotype ability to perform high, uniform yield no meter of different environmental conditions, and adaptability, genotype ability to give uniform yield in a different environmental conditions, are two common terms used to define genotype reaction in a consequence of environmental changes. Most of the models dealing with stability and adaptability are based on variation sources appearing under the influence of treatment, multivariate effects and residue. No meter which statistical model is used for GE interaction estimation, there is an opinion that no solid proof for the existence of stable genotypes obtained in breeding programs, which make some space for further investigations. There are still questions to answer dealing with definitions, sources of variation, usage value of existent models and interpretation of the results. .

  13. Both paraoxonase-1 genotype and activity do not predict the risk of future coronary artery disease; the EPIC-Norfolk Prospective Population Study.

    Directory of Open Access Journals (Sweden)

    Rakesh S Birjmohun

    Full Text Available BACKGROUND: Paraoxonase-1 (PON1 is an antioxidant enzyme, that resides on high-density lipoprotein (HDL. PON1-activity, is heavily influenced by the PON1-Q192R polymorphism. PON1 is considered to protect against atherosclerosis, but it is unclear whether this relation is independent of its carrier, HDL. In order to evaluate the atheroprotective potential of PON1, we assessed the relationships among PON1-genotype, PON1-activity and risk of future coronary artery disease (CAD, in a large prospective case-control study. METHODOLOGY/PRINCIPAL FINDINGS: Cases (n = 1138 were apparently healthy men and women aged 45-79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n = 2237 were matched by age, sex and enrollment time. PON1-activity was similar in cases and controls (60.7+/-45.3 versus 62.6+/-45.8 U/L, p = 0.3 and correlated with HDL-cholesterol levels (r = 0.16, p<0.0001. The PON1-Q192R polymorphism had a profound impact on PON1-activity, but did not predict CAD risk (Odds Ratio [OR] per R allele 0.98[0.84-1.15], p = 0.8. Using conditional logistic regression, quartiles of PON1-activity showed a modest inverse relation with CAD risk (OR for the highest versus the lowest quartile 0.77[0.63-0.95], p = 0.01; p-trend = 0.06. PON1-activity adjusted for Q192R polymorphism correlated better with HDL-cholesterol (r = 0.26, p<0.0001 and more linearly predicted CAD risk (0.79[0.64-0.98], p = 0.03; p-trend = 0.008. However, these relationships were abolished after adjustment for HDL (particles-cholesterol-size and apolipoproteinA-I (0.94[0.74-1.18], p-trend = 0.3. CONCLUSIONS/SIGNIFICANCE: This study, shows that PON1-activity inversely relates to CAD risk, but not independent of HDL, due to its close association with the HDL-particle. These data strongly suggest that a low PON1-activity is not a causal factor in atherogenesis.

  14. Genotype x environment interaction as it relates to egg production in turkeys (Meleagris gallopavo).

    Science.gov (United States)

    Case, L A; Kelly, M J; Miller, S P; Wood, B J

    2010-06-01

    Genotype x environment (GxE) interactions can reduce the accuracy of a model to predict the performance of an animal and have an undesirable influence if not accounted for when estimating breeding values. Consequently, identification of these GxE is necessary when considering a turkey breeding program. Reranking based on the genetic prediction of turkey egg production, fertility, and hatchability in different seasons was indicative of a potential GxE interaction. Quantification of the GxE interactions was based on the genetic correlation estimated when traits were expressed in different seasons. Egg production was expressed as the percentage of days with an egg produced; fertility represented the proportion of hatched eggs that contained a fertile embryo; and hatchability was defined as the percentage of fertile eggs that produced a live bird. Variance components and heritability for egg production, fertility, and hatchability were estimated using ASReml. The heritability (h(2)) of egg production was calculated to be 0.32 for both lines with the phenotypic and genetic variance, 141.3 and 45.58 (percent days with egg produced)(2) and 118.3 and 38.35 (percent days with egg produced)(2) for female and male lines, respectively. The h(2) estimates for fertility were 0.08 in both lines with and of 293.3%(2) and 24.03%(2), and 576.9%(2) and 48.43%(2) for female and male lines, respectively. The hatchability h(2), and estimates were 0.09, 267.1%(2), and 24.44%(2), respectively, for the female line and 0.15, 582.2%(2), and 90.01%(2) for the male line, respectively. Based on an animal model, the variance components were used to calculate estimated breeding values for each trait. The annual fluctuation in estimated breeding values resulted in the need to evaluate egg number, fertility, and hatchability as 2 traits, summer and winter lay. The correlation between the 2 traits was less than unity (female line: r(egg production) = 0.76, r(fertility) = -0.20, r(hatchability) = 0

  15. Cytokine profile in Egyptian hepatitis C virus genotype-4 in relation to liver disease progression

    Institute of Scientific and Technical Information of China (English)

    Abdel-Rahman N Zekri; Mohammed S El-Din Ashour; Ahmed Hassan; Hanaa M Alam El-Din; Amal MR El-Shehaby; Maha A Abu-Shady

    2005-01-01

    AIM: To observe the imbalance between T helper cell Th1 and Th2 cytokines in several chronic hepatitis disease at different stages of disease progression.METHODS: We measured the cytokine levels of Th1 (IL-2 and IL-2R), Th2 (IL-10) and the pro-inflammatory cytokines (IL-6 and IL-6R and TNF and TNF-RⅠ and Ⅱ)by the ELISA technique in the sera of 33 hepatocellular carcinoma (HCC) patients and 20 chronic liver disease (CLD) patients. In addition, 20 asymptomatic hepatitis C virus carriers and 20 healthy subjects negative for hepatitis C virus(HCV) markers served as controls.RESULTS: Anti-HCV antibodies were found to be positive in 94% of HCC cases and 75% of CLD cases.On the other hand, HCV viremia was detected using RTPCR in 67% of HCC cases and 65% of CLD cases. HBsAg was positive in 9% of HCC cases and 30% of CLD cases.Also bilharzial-Ab was positive in 55% of HCC cases,65% of CLD cases and in 70% of asymptomatic carriers (ASC). HCC patients had significantly higher values of IL-2R, TNF-RⅡ (P<0.001), and TNF-RⅠ (P>0.05), but lower TNFα (P<0.001) and IL-6 (P = 0.032) in comparison to ASC. But, in comparison to non-cancer controls, HCC patients had higher values of IL-2R, IL-6R, TNF-RⅠ and TNF-RⅡ, but lower TNF-α (P<0.001). CLD patients had higher IL-2R, TNF-RⅠ, and TNF-RⅡ (P<0.001) than ASC. But, in comparison to non-cancer controls, CLD patients had higher values of IL-2R, TNF-RⅠ and TNF-RⅡ, but lower TNF-α (P<0.001). IL-10 was higher (though not significantly) in HCC and CLD patients than in symptomatic carriers and non-cancer controls.CONCLUSION: Liver disease progression from CLD to HCC due to HCV genotype-4 infection is associated with an imbalance between Th1 and Th2 cytokines. IL-2R,TNF-RⅠ, and TNF-RⅡ could be used as potential markers.

  16. [Genotyping of Helicobacter pylori virulence factors vacA and cagA in individuals from two regions in Colombia with opposing risk for gastric cancer].

    Science.gov (United States)

    Trujillo, Esperanza; Martínez, Teresa; Bravo, María Mercedes

    2014-01-01

    The overall prevalence of Helicobacter pylori infection is high in Colombia; however, in the country´s Andean region, gastric cancer rates far surpass those in coastal areas. Helicobacter pylori genotypes cagA positive and vacA s1 and m1 are associated with an increased risk of gastric cancer. To compare the distribution of H. pylori genotypes associated with virulence in two regions in Colombia with opposing risk for gastric cancer. Four hundred and one gastric antral biopsies were obtained and analyzed from 401 individuals diagnosed with non-atrophic gastritis, atrophic gastritis and intestinal metaplasia: 256 came from the high-risk area cities of Tunja and Bogotá, and 145 from the low-risk area cities of Barranquilla, Santa Marta and Cartagena. Genotyping of virulence genes vacA and cagA was performed by PCR. No difference was observed in the frequency of H. pylori infection between the two areas (77.3% vs 77.9 %, p=non significant, ns). The presence of cagA was higher in the low-risk area (77.9% vs. 69.2 %, p=ns). The vacA s1 allele was also more prevalent in the low-risk area (61.8 % vs 72.0 %, p=ns). The vacA m1 allele was more prevalent in the high-risk area (57.2 % vs 42.8 %, p=ns). The cagA positive s1m1 combination was also more frequent in the low-risk area (48.9% vs 38.9%, p=ns). The differences in the risk of gastric cancer in these two geographic areas cannot be explained by differences in the prevalence of infection by H. pylori or by differences in the virulence of circulating strains.

  17. Brooding rumination and heart rate variability in women at high and low risk for depression: group differences and moderation by COMT genotype.

    Science.gov (United States)

    Woody, Mary L; McGeary, John E; Gibb, Brandon E

    2014-02-01

    There is growing evidence that rumination, perhaps specifically brooding rumination, is a core feature of depression and that it contributes to the development and maintenance of the disorder. A separate line of research has highlighted the role played by heart rate variability (HRV). Both brooding rumination and HRV appear to be driven by disruption in the same neural circuit, heightened amygdala reactivity combined with decreased prefrontal control, and both are highlighted in different units of analysis as reflecting the Research Domain Criteria (RDoC) construct of Loss. However, little is known about the relation among these variables. In the current study, we predicted that higher levels of brooding rumination would be associated with lower levels of HRV and that women at high risk for future depression (i.e., those with a history of past major depressive disorder [MDD]) would exhibit higher levels of brooding and lower levels of HRV. We also examined genetic influences on the variables in this model. We predicted that COMT Val158Met genotype, which has been linked to heightened amygdala reactivity and deficits in prefrontal functioning, would be associated with brooding rumination and HRV, particularly among women with a history of past MDD. The results largely supported our hypotheses, providing additional support for relations among the different units of analysis for the Loss construct.

  18. Hypoglycemia, S-ACE and ACE genotypes in a Danish nationwide population of children and adolescents with type 1 diabetes

    DEFF Research Database (Denmark)

    Johannesen, Jesper; Svensson, Jannet; Bergholdt, Regine

    2011-01-01

    OBJECTIVE: High S-ACE levels have been shown to predispose to increased risk of hypoglycemia, however; some inconsistency relates to the risk of the ACE genotype. We investigated the association between S-ACE level at diagnosis and ACE genotype to long-term risk of severe hypoglycemia in more than...

  19. Hypoglycemia, S-ACE and ACE genotypes in a Danish nationwide population of children and adolescents with type 1 diabetes

    DEFF Research Database (Denmark)

    Johannesen, Jesper; Svensson, Jannet; Bergholdt, Regine

    2011-01-01

    High S-ACE levels have been shown to predispose to increased risk of hypoglycemia, however; some inconsistency relates to the risk of the ACE genotype. We investigated the association between S-ACE level at diagnosis and ACE genotype to long-term risk of severe hypoglycemia in more than 1000...

  20. Hepatitis B virus genotypes and hepatocellular carcinoma in Thailand

    Institute of Scientific and Technical Information of China (English)

    Pisit Tangkijvanich; Varocha Mahachai; Piyawat Komolmit; Juthatip Fongsaru; Apiradee Theamboonlers; Yong Poovorawan

    2005-01-01

    AIM: The role of hepatitis B virus (HBV) genotypes on the clinical features and prognosis of patients with hepatocellular carcinoma (HCC) is currently unknown. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Thai patients.METHODS: HBV genotypes were determined by PCR-RFLP in stored sera of 93 asymptomatic carriers, 103 patients with chronic hepatitis, 60 patients with cirrhosis and 76patients with HCC. The clinical data were analyzed in relation to the HBV genotype.RESULTS: HBV genotypes C and B were predominant in Thailand, accounting for 73% and 21%, respectively. The distributions of genotypes B and C were similar in HCC patients compared to the other groups. Genotype C was significantly more common in HCC patients who were under 40 years old than genotype B (18% vs 0%, P= 0.03), but was significantly less common in patients older than 60 years (26% vs 56.5%, P= 0.01). The positive rate of hepatitis B e antigen (HBeAg) in patients with genotype C was significantly higher than that in patients with genotype B (71.6% vs 44.4%, P = 0.03 in chronic hepatitis; 56.8% vs 11.1%,P = 0.01 in cirrhosis). There were no differences between HCC patients with genotypes B and C regarding tumor staging by CLIP criteria and the overall median survival. Multivariate analyses showed that HBV genotype was not an independent prognostic factor of survival in HCC patients.CONCLUSION: Patients with genotype C had a higher positive rate of HBeAg and exhibited earlier progression of cirrhosis and HCC than those with genotype B. However,there were no differences in the risk of developing HCC and its prognosis between patients with these genotypes.

  1. Genotype-related effect of crowding stress on blood pressure and vascular function in young female rats.

    Science.gov (United States)

    Slezak, Peter; Puzserova, Angelika; Balis, Peter; Sestakova, Natalia; Majzunova, Miroslava; Dovinova, Ima; Kluknavsky, Michal; Bernatova, Iveta

    2014-01-01

    This study investigated the influence of chronic crowding stress on nitric oxide (NO) production, vascular function and oxidative status in young Wistar-Kyoto (WKY), borderline hypertensive (BHR) and spontaneously hypertensive (SHR) female rats. Five-week old rats were exposed to crowding for two weeks. Crowding elevated plasma corticosterone (PCrowding elevated NO production in all strains investigated but superoxide concentration was increased only in WKY, which resulted in reduced NO-dependent relaxation in WKY. In crowded BHR and SHR, superoxide concentration was either unchanged or reduced, respectively, but NO-dependent relaxation was unchanged in both BHR and SHR versus their respective control group. This study points to genotype-related differences in stress vulnerability in young female rats. The most pronounced negative influence of stress was observed in BHR despite preserved endothelial function.

  2. Cfh genotype interacts with dietary glycemic index to modulate age-related macular degeneration-like features in mice

    Science.gov (United States)

    Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide. Genetics and diet contribute to the relative risk for developing AMD, but their interactions are poorly understood. Genetic variations in Complement Factor H (CFH), and dietary glycemic index (GI) are major ris...

  3. Content of the cyanogenic glucoside amygdalin in almond seeds related to the bitterness genotype

    OpenAIRE

    Arrázola, Guillermo; Sánchez P., Raquel; Dicenta, Federico; Grané, Nuria

    2012-01-01

    Almond kernels can be sweet, slightly bitter or bitter. Bitterness in almond (Prunus dulcis Mill.) and other Prunus species is related to the content of the cyanogenic diglucoside amygdalin. When an almond containing amygdalin is chopped, glucose, benzaldehyde (bitter flavor) and hydrogen cyanide (which is toxic) are released. This two-year-study with 29 different almond cultivars for bitterness was carried out in order to relate the concentration of amygdalin in the kernel with the phenotype...

  4. Content of the cyanogenic glucoside amygdalin in almond seeds related to the bitterness genotype

    OpenAIRE

    Guillermo Arrázola; Raquel Sánchez P; Federico Dicenta; Nuria Grané

    2012-01-01

    Almond kernels can be sweet, slightly bitter or bitter. Bitterness in almond (Prunus dulcis Mill.) and other Prunus species is related to the content of the cyanogenic diglucoside amygdalin. When an almond containing amygdalin is chopped, glucose, benzaldehyde (bitter flavor) and hydrogen cyanide (which is toxic) are released. This two-year-study with 29 different almond cultivars for bitterness was carried out in order to relate the concentration of amygdalin in the kernel with the phenotype...

  5. Gene polymorphisms related to angiogenesis, inflammation and thrombosis that influence risk for oral cancer.

    Science.gov (United States)

    Vairaktaris, E; Serefoglou, Z; Avgoustidis, D; Yapijakis, C; Critselis, E; Vylliotis, A; Spyridonidou, S; Derka, S; Vassiliou, S; Nkenke, E; Patsouris, E

    2009-03-01

    Genetic association studies have implicated functional DNA polymorphisms in genes encoding factors related to angiogenesis, inflammation and thrombosis with increased risk for oral squamous cell carcinoma (OSCC). This study examines possible interactions between nine such genotype polymorphisms and their combinatory effect in assessing the OSCC risk in a European population. OSCC cases (N=162) and healthy controls (N=168) of comparable age, gender, and ethnicity (Greeks and Germans) were studied. Multivariate logistic regression models were constructed in order to assess the contribution of homozygous or heterozygous variant genotypes of polymorphisms MMP-1 (-1607 1G/2G), MMP-3 (-1171 5A/6A), MMP-9 (-1562C/T), TIMP-2 (-418C/G), VEGF (+936C/T), GPI-alpha (+807C/T), PAI-1 (4G/5G), ACE (intron 16D/I) and TAFI (+325C/T) upon overall, early and advanced stages of OSCC. Four out of nine polymorphisms affecting PAI-1, MMP-9, TIMP-2 and ACE expression contributed significantly in OSCC prediction in the various logistic regression models. Based on these findings and previous reports, possible interactions of the implicated factors leading to OSCC development, as well as an algorithm of risk estimation are discussed.

  6. [The different genotypes of MTHFR 1298A>C and PON1 -108C>T polymorphisms confer the increased risk of the abdominal aortic aneurysm in the smoking and nonsmoking persons].

    Science.gov (United States)

    Strauss, Ewa; Waliszewski, Krzysztof; Pawlak, Andrzej L

    2005-01-01

    In abdominal aortic aneurysm (AAA) both the etiology and the pathogenesis are of the multifactorial character. The genetic component in the determination of this disease is proven by its familial occurrence. Smoking represents the best recognized risk factor of the AAA development. Increased concentrations of homocysteine (Hcy) in plasma are the common finding in these patients. It is assumed that the Hcy thiolactone, the most reactive metabolite of Hcy, may participate in the aortic wall destruction in AAA. The polymorphic variants of the methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C) influence tissue concentrations of the Hcy. Paraoxonase (PON1), the enzyme associated in plasma with the HDL fraction, as lactonase detoxicates the Hcy thiolactone. The promotor polymorphism of PON1 - 108C>T gene may determine the lower activity of this enzyme. In the case-control study of 106 patients with AAA and 97 healthy persons, the effects of selected genetic and nongenetic risk factors on development of AAA were assessed, considering the possibilities of interaction between them. It was found, that the arterial hypertension, cigarette smoking and the lower HDL fraction are independent risk factors of AAA. The arterial hypertension was a risk factor both in the smoking and the nonsmoking males, whereas the lower HDL fraction has been the risk factor only for the smoking men. By the multivariate analysis in the nonsmoking males the MTHFR 1298 AC and CC genotypes increased the risk of AAA development 4,8-fold in relation to the MTHFR 1298 AA nonsmoking males. In reference to the genotypes of the expected high impact on the metabolism of Hcy and of Hcy thiolactone, the genotypes of MTHFR 677TT and PON1 -108CT and TT were more frequent in smoking ones, but the difference was not significant. This observation fits with the assumption that the influence of smoking on the occurrence of AAA prevails over that of genetic variability. When the patients age was considered

  7. Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.

    Science.gov (United States)

    Machiela, Mitchell J; Hofmann, Jonathan N; Carreras-Torres, Robert; Brown, Kevin M; Johansson, Mattias; Wang, Zhaoming; Foll, Matthieu; Li, Peng; Rothman, Nathaniel; Savage, Sharon A; Gaborieau, Valerie; McKay, James D; Ye, Yuanqing; Henrion, Marc; Bruinsma, Fiona; Jordan, Susan; Severi, Gianluca; Hveem, Kristian; Vatten, Lars J; Fletcher, Tony; Koppova, Kvetoslava; Larsson, Susanna C; Wolk, Alicja; Banks, Rosamonde E; Selby, Peter J; Easton, Douglas F; Pharoah, Paul; Andreotti, Gabriella; Freeman, Laura E Beane; Koutros, Stella; Albanes, Demetrius; Mannisto, Satu; Weinstein, Stephanie; Clark, Peter E; Edwards, Todd E; Lipworth, Loren; Gapstur, Susan M; Stevens, Victoria L; Carol, Hallie; Freedman, Matthew L; Pomerantz, Mark M; Cho, Eunyoung; Kraft, Peter; Preston, Mark A; Wilson, Kathryn M; Gaziano, J Michael; Sesso, Howard S; Black, Amanda; Freedman, Neal D; Huang, Wen-Yi; Anema, John G; Kahnoski, Richard J; Lane, Brian R; Noyes, Sabrina L; Petillo, David; Colli, Leandro M; Sampson, Joshua N; Besse, Celine; Blanche, Helene; Boland, Anne; Burdette, Laurie; Prokhortchouk, Egor; Skryabin, Konstantin G; Yeager, Meredith; Mijuskovic, Mirjana; Ognjanovic, Miodrag; Foretova, Lenka; Holcatova, Ivana; Janout, Vladimir; Mates, Dana; Mukeriya, Anush; Rascu, Stefan; Zaridze, David; Bencko, Vladimir; Cybulski, Cezary; Fabianova, Eleonora; Jinga, Viorel; Lissowska, Jolanta; Lubinski, Jan; Navratilova, Marie; Rudnai, Peter; Szeszenia-Dabrowska, Neonila; Benhamou, Simone; Cancel-Tassin, Geraldine; Cussenot, Olivier; Bueno-de-Mesquita, H Bas; Canzian, Federico; Duell, Eric J; Ljungberg, Börje; Sitaram, Raviprakash T; Peters, Ulrike; White, Emily; Anderson, Garnet L; Johnson, Lisa; Luo, Juhua; Buring, Julie; Lee, I-Min; Chow, Wong-Ho; Moore, Lee E; Wood, Christopher; Eisen, Timothy; Larkin, James; Choueiri, Toni K; Lathrop, G Mark; Teh, Bin Tean; Deleuze, Jean-Francois; Wu, Xifeng; Houlston, Richard S; Brennan, Paul; Chanock, Stephen J; Scelo, Ghislaine; Purdue, Mark P

    2017-08-07

    Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, pbody of evidence indicating some aspect of longer telomere length is important for RCC risk. Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma. Published by Elsevier B.V.

  8. The relation of risk assessment and health impact assessment

    DEFF Research Database (Denmark)

    Ádám, Balázs; Gulis, Gabriel

    2013-01-01

    their relationship. The experiences accumulated during the preparation of several case studies in a large scale international project (RAPID) are used for argumentation and formulation of recommendations on how risk assessment can be systematically integrated into the HIA process. Risk assessment uses well...... than assessing a present situation. As part of this process, however, methods applied in risk assessment are used. Risk assessment typically characterises relation of a well-defined risk factor to a well-defined health outcome. Within HIA usually several individual risk assessments are needed...... in the risk appraisal phase to describe effects of various factors on different health outcomes. Consequently, HIA is typically led by a large, preferably intersectoral steering group with representatives of communities at risk. Risk assessment, in contrary, is mainly a licensed scientific process completed...

  9. Genotype-Property Patient-Phenotype Relations Suggest that Proteome Exhaustion Can Cause Amyotrophic Lateral Sclerosis

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2015-01-01

    number, expressed as an exponential function of the experimental stabilities (R-2 = 0.31, p = 0.002), and this phenotype is further aggravated by charge (R-2 = 0.51, p = 1.8 x 10-5). This finding suggests that disease relates to the copy number of misfolded proteins. Exhaustion of motor neurons due...

  10. CONCEPTS AND RISKS RELATED TO TRADEMARKS

    OpenAIRE

    Mihaela-Daciana BOLOS; Bradut-Vasile BOLOS

    2011-01-01

    We explore issues related to trademarks, from accounting recognition perspective. The research is a conceptual exploration emphasizing some issues on intellectual property interferences with accounting and some aspects that should be considered in auditpractice

  11. Power and related statistical properties of conditional likelihood score tests for association studies in nuclear families with parental genotypes.

    Science.gov (United States)

    Li, Z; Gastwirth, J L; Gail, M H

    2005-05-01

    Both population based and family based case control studies are used to test whether particular genotypes are associated with disease. While population based studies have more power, cryptic population stratification can produce false-positive results. Family-based methods have been introduced to control for this problem. This paper presents the full likelihood function for family-based association studies for nuclear families ascertained on the basis of their number of affected and unaffected children. The likelihood of a family factors into the probability of parental mating type, conditional on offspring phenotypes, times the probability of offspring genotypes given their phenotypes and the parental mating type. The first factor can be influenced by population stratification, whereas the latter factor, called the conditional likelihood, is not. The conditional likelihood is used to obtain score tests with proper size in the presence of population stratification (see also Clayton (1999) and Whittemore & Tu (2000)). Under either the additive or multiplicative model, the TDT is known to be the optimal score test when the family has only one affected child. Thus, the class of score tests explored can be considered as a general family of TDT-like procedures. The relative informativeness of the various mating types is assessed using the Fisher information, which depends on the number of affected and unaffected offspring and the penetrances. When the additive model is true, families with parental mating type Aa x Aa are most informative. Under the dominant (recessive) model, however, a family with mating type Aa x aa(AA x Aa) is more informative than a family with doubly heterozygous (Aa x Aa) parents. Because we derive explicit formulae for all components of the likelihood, we are able to present tables giving required sample sizes for dominant, additive and recessive inheritance models.

  12. Variations in Concentration and Distribution of Health-Related Elements Affected by Environmental and Genotypic Differences in Rice Grains

    Institute of Scientific and Technical Information of China (English)

    REN Xue-liang; LIU Qing-long; WU Dian-xing; SHU Qing-yao

    2006-01-01

    A research work was conducted to investigate the variations in concentration and distribution of health-related elements affected by environmental and genotypic differences in rice grains. The grain of Xieqingzao B (indica rice variety) and Xiushui 110 (japonica rice variety) were divided into: hull, bran and milled rice, based on the conventional rice consumption and process. Xieqingzao B was grown at four different locations, and at one location, it was planted in the same field and season as Xiushui 110. In addition, another four indica and four japonica varieties were cultivated in the same field and time to analyze the elements in milled rice. The average concentrations of total P and phytic acid P were the highest in the bran, followed by milled rice and hull; Zn, K, Mg, and As concentrations were the highest in bran, followed by hull and milled rice, while Fe, Ca, and Cu concentrations were the highest in the hull, but similar in bran and milled rice. The result indicated that genotype and environment significantly affected the concentrations of all the tested elements, while the distribution of the above elements in grains was not in the same order as concentration. Moreover, all the elements except 97.7% of Cu and 93.2% of Fe was deposited in the hull on average, were mostly distributed either in the bran (37.3% and 57.7% for K and phytic acid P) or in milled rice (41.7%, 42.6%, 40.3%, 49.8% for Zn, Mg, As, total P, respectively).

  13. Prevalence of HPV Infection and High Risk HPV Genotypes (16, 18, among Monogamous and Polygamous Women, In Zabol, Iran

    Directory of Open Access Journals (Sweden)

    I Shahramian

    2011-09-01

    Full Text Available Background: This study was performed to compare the prevalence of HPV infection and high risk HPV genotypes [16, 18] between monogamous and polygamous women, in Zabol, Iran.Methods: This cross sectional study was conducted in Zabol in 2006 - 2007. Two hundred sixty five married women attend­ing the Gynecology Clinic for Cervical Disease Screening entered to this study. One hundred sixty two cases had mo­nogamous, and 103 had polygamous husbands. HPV PCR samples were obtained from scrape of papsmear speci­mens. The biotinylated primers MY09/MY11, GP5+/GP6+, were utilized to enable amplification and detection of posi­tive PCR products. Confirmation of HPV-16 and -18 were done by type-specific PCR primers HPV-16/F, HPV-16/R and HPV-18/F, HPV-18/R.Results: Prevalence of HPV infection in monogamous and polygamous groups was 29% and 37.9%, respectively. The most HPV infection was found in 15-25 years group. The most prevalence of infection in monogamous group was HPV-18 and HPV- non16, 18 in 15-25 years, and HPV-16 in 26-35 years group. In polygamous group the most preva­lent type was HPV-16, 18 in 15-25 years group. The most prevalent HPV-16 was seen in sever inflammation and dys­plasia cytology in both groups.Conclusion: Prevalence of HPV infection in Zabol is high, and in women with polygamous husbands group is slightly more than monogamous. Screening for this infection must be recommended in this region of Iran.

  14. Human Papillomavirus (HPV) Infection: Molecular Epidemiology, Genotyping, Seroprevalence and Associated Risk Factors among Arab Women in Qatar

    Science.gov (United States)

    Acharya, Anushree; Skariah, Sini; Dargham, Soha R.; Abu-Raddad, Laith J.; Mohamed-Nady, Nady; Amuna, Paul; Al-Thani, Asma A. J.; Sultan, Ali A.

    2017-01-01

    Human Papillomavirus (HPV) infections are known to cause cervical cancer worldwide, however, limited information is currently available on prevalence, types distribution and risk factors for HPV infection in the Arab countries. We conducted a cross-sectional observational study exclusively of women of Arabic origin residing in Qatar (n = 406) who were selected from the Women’s Hospital at Hamad Medical Corporation (HMC) and Health Centers of the Primary Health Care Corporation in Doha, Qatar over the period March 2013 to August 2014. Socio-demographic, behavioral and clinical data were collected. Four hundred and six cervical smears and 292 blood samples were included in the study. HPV typing was done using HPV type-specific primers-based real-time PCR, and Sanger sequencing. HPV-IgG and IgM were quantified using ELISA assays. The prevalence of HPV infection amongst Qatari and non-Qatari Arab women were 9.8% and 6.1%, respectively and 7.6% and 16.7% in women with normal and abnormal cytology, respectively. HPV 81 was the most commonly found genotype in women with normal cytology (34.5%), whereas HPV 81, 16 and 59 in women with abnormal cytology (25.0% each). All the HPV DNA positive women were seronegative and HPV-IgG prevalence was higher in Qatari women than in non-Qatari Arab women. None of the studied factors had any significant association with HPV-DNA positivity or HPV-IgG seropositivity. The overall identified HPV DNA prevalence and HPV seroprevalence among Arab women in Qatar were on the low side compared to global levels. PMID:28046025

  15. Brain tumour risk in relation to mobile telephone use

    DEFF Research Database (Denmark)

    Johansen, Christoffer

    2010-01-01

    The rapid increase in mobile telephone use has generated concern about possible health risks related to radiofrequency electromagnetic fields from this technology.......The rapid increase in mobile telephone use has generated concern about possible health risks related to radiofrequency electromagnetic fields from this technology....

  16. Dense genotyping of immune-related loci identifies variants associated with clearance of HPV among HIV-positive women in the HIV epidemiology research study (HERS.

    Directory of Open Access Journals (Sweden)

    Staci L Sudenga

    Full Text Available Persistent high-risk human papillomavirus (HR-HPV is a necessary and causal factor of cervical cancer. Most women naturally clear HPV infections; however, the biological mechanisms related to HPV pathogenesis have not been clearly elucidated. Host genetic factors that specifically regulate immune response could play an important role. All HIV-positive women in the HIV Epidemiology Research Study (HERS with a HR-HPV infection and at least one follow-up biannual visit were included in the study. Cervicovaginal lavage samples were tested for HPV using type-specific HPV hybridization assays. Type-specific HPV clearance was defined as two consecutive HPV-negative tests after a positive test. DNA from participants was genotyped for 196,524 variants within 186 known immune related loci using the custom ImmunoChip microarray. To assess the influence of each single-nucleotide polymorphism (SNP with HR-HPV clearance, the Cox proportional hazards model with the Wei-Lin-Weissfeld approach was used, adjusting for CD4+ count, low risk HPV (LR-HPV co-infection, and relevant confounders. Three analytical models were performed: race-specific (African Americans (n = 258, European Americans (n = 87, Hispanics (n = 55, race-adjusted combined analysis, and meta-analysis of pooled independent race-specific analyses. Women were followed for a median time of 1,617 days. Overall, three SNPs (rs1112085, rs11102637, and rs12030900 in the MAGI-3 gene and one SNP (rs8031627 in the SMAD3 gene were associated with HR-HPV clearance (p<10(-6. A variant (rs1633038 in HLA-G were also significantly associated in African American. Results from this study support associations of immune-related genes, having potential biological mechanism, with differential cervical HR-HPV infection outcomes.

  17. Cervical human papillomavirus infection among young women engaged in sex work in Phnom Penh, Cambodia: prevalence, genotypes, risk factors and association with HIV infection

    Science.gov (United States)

    2012-01-01

    Background Although cervical cancer is the leading cancer in Cambodia, most women receive no routine screening for cervical cancer and few treatment options exist. Moreover, nothing is known regarding the prevalence of cervical HPV or the genotypes present among women in the country. Young sexually active women, especially those with multiple sex partners are at highest risk of HPV infection. We examine the prevalence and genotypes of cervical HPV, as well as the associated risk factors among young women engaged in sex work in Phnom Penh, Cambodia. Methods We conducted a cross-sectional study among 220 young women (15–29 years) engaged in sex work in different venues including brothels or entertainment establishments, and on a freelance basis in streets, parks and private apartments. Cervical specimens were collected using standard cytobrush technique. HPV DNA was tested for by polymerase chain reaction (PCR) and genotyping using type-specific probes for 29 individual HPV types, as well as for a mixture of 10 less common HPV types. All participants were also screened for HIV status using blood samples. Multivariate logistic regression analyses were conducted to assess risk factors for any or multiple HPV infection. Results The prevalence of cervical HPV 41.1%. HPV 51 and 70 were the most common (5.0%), followed by 16 (4.6%), 71 (4.1%) and 81 (3.7%). Thirty-six women (16.4%) were infected with multiple genotypes and 23.3% were infected with at least one oncogenic HPV type. In multivariate analyses, having HIV infection and a higher number of sexual partners were associated with cervical HPV infection. Risk factors for infection with multiple genotypes included working as freelance female sex workers (FSW) or in brothels, recent binge use of drugs, high number of sexual partners, and HIV infection. Conclusions This is the first Cambodian study on cervical HPV prevalence and genotypes. We found that HPV infection was common among young FSW, especially among women

  18. Pro-Inflammatory Interleukin-1 Genotypes Potentiate the Risk of Coronary Artery Disease and Cardiovascular Events Mediated by Oxidized Phospholipids and Lipoprotein (a)

    Science.gov (United States)

    Tsimikas, Sotirios; Duff, Gordon W.; Berger, Peter B.; Rogus, John; Huttner, Kenneth; Clopton, Paul; Brilakis, Emmanuel; Kornman, Kenneth S; Witztum, Joseph L

    2014-01-01

    Objective To assess the influence of pro-inflammatory IL-1 genotype status on the risk of CAD, defined as >50% diameter stenosis, and cardiovascular events mediated by OxPL and Lp(a). Background Oxidized phospholipids (OxPL) are pro-inflammatory, circulate on lipoprotein (a) [Lp(a)] and mediate coronary artery disease (CAD). Genetic variations in the interleukin-1 (IL-1) region are associated with increased inflammatory mediators. Methods IL-1 genotypes, OxPL on apolipoprotein B-100 (OxPL/apoB) and Lp(a) levels were measured in 499 patients undergoing coronary angiography. The composite genotype termed IL-1(+) was defined by three single nucleotide polymorphisms (SNPs) in the IL-1 gene cluster associated with higher levels of pro-inflammatory cytokines. All other IL-1 genotypes were termed IL-1(−). Results Among IL-1(+) patients, the highest quartile of OxPL/apoB was significantly associated with a higher risk of CAD compared to the lowest quartile (OR 2.84, P=0.001). This effect was accentuated in patients ≤60 years old (OR 7.03, P60 years old. In IL-1(+) patients ≤60 years old, after adjusting for established risk factors, high sensitivity C-reactive protein and Lp(a), OxPL/apoB remained an independent predictor of CAD. IL-1(+) patients above the median OxPL/apoB presented to the cardiac catheterization laboratory a mean of 3.9 years earlier (P=0.002) and had worse 4-year event-free survival (death, MI, stroke, and revascularization) compared to other groups (P=0.006). Conclusion Our study suggests that IL-1 genotype status can stratify population risk for CAD and cardiovascular events mediated by OxPL. These data suggest a clinically-relevant biological link between pro-inflammatory IL-1 genotypes, oxidation of phospholipids, Lp(a) and genetic predisposition to CAD and cardiovascular events. PMID:24530664

  19. Cervical human papillomavirus infection among young women engaged in sex work in Phnom Penh, Cambodia: prevalence, genotypes, risk factors and association with HIV infection

    Directory of Open Access Journals (Sweden)

    Couture Marie-Claude

    2012-07-01

    Full Text Available Abstract Background Although cervical cancer is the leading cancer in Cambodia, most women receive no routine screening for cervical cancer and few treatment options exist. Moreover, nothing is known regarding the prevalence of cervical HPV or the genotypes present among women in the country. Young sexually active women, especially those with multiple sex partners are at highest risk of HPV infection. We examine the prevalence and genotypes of cervical HPV, as well as the associated risk factors among young women engaged in sex work in Phnom Penh, Cambodia. Methods We conducted a cross-sectional study among 220 young women (15–29 years engaged in sex work in different venues including brothels or entertainment establishments, and on a freelance basis in streets, parks and private apartments. Cervical specimens were collected using standard cytobrush technique. HPV DNA was tested for by polymerase chain reaction (PCR and genotyping using type-specific probes for 29 individual HPV types, as well as for a mixture of 10 less common HPV types. All participants were also screened for HIV status using blood samples. Multivariate logistic regression analyses were conducted to assess risk factors for any or multiple HPV infection. Results The prevalence of cervical HPV 41.1%. HPV 51 and 70 were the most common (5.0%, followed by 16 (4.6%, 71 (4.1% and 81 (3.7%. Thirty-six women (16.4% were infected with multiple genotypes and 23.3% were infected with at least one oncogenic HPV type. In multivariate analyses, having HIV infection and a higher number of sexual partners were associated with cervical HPV infection. Risk factors for infection with multiple genotypes included working as freelance female sex workers (FSW or in brothels, recent binge use of drugs, high number of sexual partners, and HIV infection. Conclusions This is the first Cambodian study on cervical HPV prevalence and genotypes. We found that HPV infection was common among young FSW

  20. Does hepatitis C viremia or genotype predict the risk of mortality in individuals co-infected with HIV?

    DEFF Research Database (Denmark)

    Rockstroh, Jürgen K; Peters, Lars; Grint, Daniel

    2013-01-01

    The influence of HCV-RNA levels and genotype on HCV disease progression is not well studied. The prognostic value of these markers was investigated in HIV/HCV co-infected individuals from the EuroSIDA cohort.......The influence of HCV-RNA levels and genotype on HCV disease progression is not well studied. The prognostic value of these markers was investigated in HIV/HCV co-infected individuals from the EuroSIDA cohort....

  1. Prevalence of High-Risk Genotypes of Human Papillomavirus: Women Diagnosed with Premalignant and Malignant Pap Smear Tests in Southern Ecuador

    Science.gov (United States)

    Loján González, Cisne; Córdova Rodríguez, Ana; Acurio Páez, Katherine; Arévalo, Ana Paulina; Bobokova, Jana

    2017-01-01

    Human papillomavirus (HPV) is the primary infectious agent for the development of cervical cancer, although the presence of the virus alone is insufficient for viral development and proliferation; this can be attributed to the increase in potential oncogenic risk, along with other risk factors. In the present investigation, the prevalence of high-risk HPV was determined from samples of premalignant or malignant cervical cytology in women from the southern region of Ecuador. The kit we used was able to detect genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. In addition, 64.5% of the analyzed samples were positive for HPV, with genotypes 16 and 18 being the most prevalent (16 was detected in 148 samples and 18 in 108). Genotypes 58 and 51 were the third most frequent simple and multiple infections, respectively. The data are very similar to those obtained worldwide, suggesting that the strategy of sex education, and the use of vaccines as primary prevention agents, could significantly decrease the incidence and mortality rate of cervical cancer in the southern region of Ecuador. PMID:28717342

  2. Prevalence of High-Risk Genotypes of Human Papillomavirus: Women Diagnosed with Premalignant and Malignant Pap Smear Tests in Southern Ecuador

    Directory of Open Access Journals (Sweden)

    Paola Dalgo Aguilar

    2017-01-01

    Full Text Available Human papillomavirus (HPV is the primary infectious agent for the development of cervical cancer, although the presence of the virus alone is insufficient for viral development and proliferation; this can be attributed to the increase in potential oncogenic risk, along with other risk factors. In the present investigation, the prevalence of high-risk HPV was determined from samples of premalignant or malignant cervical cytology in women from the southern region of Ecuador. The kit we used was able to detect genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. In addition, 64.5% of the analyzed samples were positive for HPV, with genotypes 16 and 18 being the most prevalent (16 was detected in 148 samples and 18 in 108. Genotypes 58 and 51 were the third most frequent simple and multiple infections, respectively. The data are very similar to those obtained worldwide, suggesting that the strategy of sex education, and the use of vaccines as primary prevention agents, could significantly decrease the incidence and mortality rate of cervical cancer in the southern region of Ecuador.

  3. THE RISK OF EARLY LIVER ALLOGRAFT DYSFUNCTION IS ASSOCIATED WITH THE TLR-4 GENE GENOTYPE IN THE RS913930 SEQUENCE AND IS IMPLEMENTED VIA HMGB1 NUCLEAR PROTEIN, KUPFFER CELLS AND IL-23 ACTIVATION

    Directory of Open Access Journals (Sweden)

    A. E. Shcherba

    2016-01-01

    Full Text Available Aim. To evaluate the associations of genotypes of clinically relevant nucleotides rs11536865, rs913930 and rs5030717 of the TLR-4 gene with the risk of development and severity of early allograft dysfunction after liver transplantation. Materials and methods. A case-control study enrolling 71 patients was organized. Inclusion criteria: DBD liver transplantation. Exclusion criteria: living related liver transplantation, reduced graft transplantation, recipient’s age fewer than 18. Results. Within rs5030717 there were identifi ed three genotypes: AA (81.6% and two genotypes with the minor G-allele: AG (12.6% and GG (5.6%. Within rs913930 there identi- fi ed three genotypes: TT (59.1% and two genotypes with the minor C-allele: C/T (29.5% and CC (11.2%. The rs11536865 studying revealed no polymorphism (GG genotype. The early allograft liver dysfunction (EAD developed in 19.7% of patients, the severe EAD in 11.2% of patients, septic complications in 14%, acute cellular rejection in 23.9% of cases. The C/T genotype of the TLR-4 gene in the SNP rs913930 sequence was closely associated with the EAD development (OR 4.8 to 1; p = 0.047; 95% CI 1–23.4. Рatients with the donor’s liver C/T genotype had a reliably higher proportion (% of the HMGB1 positive hepatocytes in the donor’s bioptate, 21 (17–29% vs the СС+TT genotypes, 16 (10–19% (Mann–Whitney test, p = 0.01. The CD68 expression in the liver bioptate at the donor’s stage was reliably higher in the carriers of heterozygotes in the SNP rs913930 (C/T genotype and in the SNP rs5030717 (AG genotype, (Mann–Whitney test, p = 0.03. Signifi cant positive correlation between the CD68 expression in the donor’s liver bioptates and the IL-23 level in the hepatic vein has been determined in an hour after the portal reperfusion (ρ = 0.62; p = 0.04 as well as between the HMGB1 expression in the donor’s liver bioptates and the АSТ level in 24 hours after the reperfusion (r = 0.4; p = 0

  4. Tissue distribution, gender- and genotype-dependent expression of autophagy-related genes in avian species.

    Directory of Open Access Journals (Sweden)

    Alissa Piekarski

    Full Text Available As a result of the genetic selection of broiler (meat-type breeders chickens for enhanced growth rate and lower feed conversion ratio, it has become necessary to restrict feed intake. When broilers are fed ad libitum, they would become obese and suffer from several health-related problems. A vital adaptation to starvation is autophagy, a self-eating mechanism for recycling cellular constituents. The autophagy pathway has witnessed dramatic growth in the last few years and extensively studied in yeast and mammals however, there is a paucity of information in avian (non-mammalian species. Here we characterized several genes involved in autophagosome initiation and elongation in Red Jungle fowl (Gallus gallus and Japanese quail (coturnix coturnix Japonica. Both complexes are ubiquitously expressed in chicken and quail tissues (liver, leg and breast muscle, brain, gizzard, intestine, heart, lung, kidney, adipose tissue, ovary and testis. Alignment analysis showed high similarity (50.7 to 91.5% between chicken autophagy-related genes and their mammalian orthologs. Phylogenetic analysis demonstrated that the evolutionary relationship between autophagy genes is consistent with the consensus view of vertebrate evolution. Interestingly, the expression of autophagy-related genes is tissue- and gender-dependent. Furthermore, using two experimental male quail lines divergently selected over 40 generations for low (resistant, R or high (sensitive, S stress response, we found that the expression of most studied genes are higher in R compared to S line. Together our results indicate that the autophagy pathway is a key molecular signature exhibited gender specific differences and likely plays an important role in response to stress in avian species.

  5. Cultivar Differences in Plant Transpiration Rate at High Relative Air Humidity Are Not Related to Genotypic Variation in Stomatal Responsiveness

    DEFF Research Database (Denmark)

    Gebraegziabher, Habtamu Giday; Kjær, Katrine Heinsvig; Ottosen, Carl-Otto;

    2015-01-01

    Plants grown at high relative air humidity (RH) often show disturbed water relations due to less responsive stomata. The attenuation of stomatal responsiveness as a result of high RH during leaf expansion depends on the cultivar. We hypothesized that tolerant cultivars to high RH experience a lower...... a given cultivar, Tleaf was generally higher, (1.5-3.7°C) at high as compared to moderate RH. Following desiccation, leaf weight loss was differentially enhanced (8-66%) in high RH-grown plants, indicating a wide variation in high RH tolerance. High RH mainly decreased plant water loss during the light...

  6. Association between Variants in Atopy-Related Immunologic Candidate Genes and Pancreatic Cancer Risk.

    Directory of Open Access Journals (Sweden)

    Michelle Cotterchio

    Full Text Available Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk.A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry, and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls. Following an exhaustive literature review, SNPs in 180 candidate genes were pre-screened using dbGaP pancreas cancer GWAS data; 147 SNPs in 56 allergy-related immunologic genes were retained and genotyped. Logistic regression was used to estimate age-adjusted odd ratio (AOR for each variant and false discovery rate was used to adjust Wald p-values for multiple testing. Subsequently, a risk allele score was derived based on statistically significant variants.18 SNPs in 14 candidate genes (CSF2, DENND1B, DPP10, FLG, IL13, IL13RA2, LRP1B, NOD1, NPSR1, ORMDL3, RORA, STAT4, TLR6, TRA were significantly associated with pancreas cancer risk. After adjustment for multiple comparisons, two LRP1B SNPs remained statistically significant; for example, LRP1B rs1449477 (AA vs. CC: AOR=0.37, 95% CI: 0.22-0.62; p (adjusted=0.04. Furthermore, the risk allele score was associated with a significant reduction in pancreas cancer risk (p=0.0007.Preliminary findings suggest certain atopy-related variants may be associated with pancreas cancer risk. Further studies are needed to replicate this, and to elucidate the biology behind the growing body of epidemiologic evidence suggesting allergies may reduce pancreatic cancer risk.

  7. Risk related behaviour under different ambient scent conditions

    Directory of Open Access Journals (Sweden)

    Alina Gagarina

    2016-09-01

    Full Text Available Abstract The article analyses the effect of two ambient scents (peppermint and vanilla and their intensiveness on risk related behaviour that is expressed through selected decision making heuristics. Purpose of the article: The purpose of this article is to identify the relationship of ambient scent type and intensiveness with risk related behaviour that is expressed through selected decision making heuristics. Methodology/methods: 2x2 factorial experiment with control group was run. Ambient scent type (vanilla vs. peppermint and intensiveness (8 (1mg vs. 16 sprays (2mg of scent concentrate in the same room were manipulated as between subject variables. Risk aversion, effect of anchoring heuristic on bidding, and affect (risk and benefit heuristics were tracked as dependent variables. Scientific aim: To identify whether ambient scent type and intensiveness have effect on risk related behaviour. Findings: Evidence suggests that there are effects of ambient scent on risk related behaviour, thus fulfilling the missing gap to relate ambient environment to decision making heuristics when risks are involved. However, not all heuristics were affected by experimental conditions. Subjects were bidding significantly higher amounts under low anchor conditions, when peppermint scent was around (if compared to vanilla group. Affect risk was perceived as lower in peppermint ambient scent conditions, if compared to the control group. Intensity of ambient scent also had influence on affect risk: subjects perceived less risk under high scent intensity conditions. Conclusions: By manipulating ambient scent, marketers may reduce or increase consumers risk perception and behaviour and as a consequence influence their purchase decisions. Marketers could use peppermint scent in high intensiveness in the situations where they want consumers to undertake higher risks (expensive purchases, gambling, insurance, since stakes were higher under peppermint ambient scent

  8. Hepatitis C Virus Genotypes

    Directory of Open Access Journals (Sweden)

    Kayhan Azadmanesh

    2005-09-01

    the ultimate source of the virus's genetic diversity. HCV circulates as a heterogeneous population of genetically different but closely related genomes known as the quasispecies(15.As only 30-35% of nucleotides actually differ, there is obviously considerable heterogeneity in evolutionary rates among nucleotide sites in the genome. This heterogeneity is the result of variable evolutionary constraints. The 5'-UTR contains extensive secondary RNA structure and is correspondingly the slowest evolving genomic region(16. The next slowest region is the C (Core gene, which evolves three times faster than the 5'- UTR. The envelope genes E1 and E2 constitute the most diverse genome region and evolve about nine times faster than the 5'-UTR(16, probably as a result of their presumed role in evading the host immune response. Genomic Heterogeneity and ClassificationSystemsShortly after its discovery in 1989, it became clear that HCV had substantial nucleotide sequence diversity, with only 66 to 80% overall sequencesimilarity among strains belonging to different genotypes or subtypes(17. HCV isolates show four levels of genomic variations: types, subtypes, isolates, andquasispecies. The overall sequence similarities over complete genomic sequences are at least 91% within quasispecies, approximately 79% (range, 77 to 80% between subtypes, and about 68% (range, 66 to 69% between different types. This quasispecies is composed of a group of heterogeneous RNA sequences centered around a dominant nucleotide sequence that changes, throughout the course of the infection, under the selective pressure of the host immune system(18. More than one genotype can be found in the circulations of some HCV-infected patients, particularly in individuals who have received multiple transfusions and intravenous drug users. These are referred to as mixed-genotype infections(19, 20.The lack of a routinely available cell culture system and an easily available animal model has rendered classification of HCV

  9. A Toolbox for Health Risk Related Decisions

    Science.gov (United States)

    1996-05-01

    context of this paradiagm in order to estimate "toxic equivalency factors" for the class of materials known as dioxins . The many dioxin congeners are...the toxic equivalent factor (our relative potency) concept as promulgated by the EPA for congeners of PCBs, dioxins and furans represents a...these ideas. In the conceptual approach, the biomarkers in the table are used to "translate" the data fiom higher dose animal and human data to the

  10. Cultivar Differences in Plant Transpiration Rate at High Relative Air Humidity Are Not Related to Genotypic Variation in Stomatal Responsiveness

    DEFF Research Database (Denmark)

    Gebraegziabher, Habtamu Giday; Kjær, Katrine Heinsvig; Ottosen, Carl-Otto

    2015-01-01

    a given cultivar, Tleaf was generally higher, (1.5-3.7°C) at high as compared to moderate RH. Following desiccation, leaf weight loss was differentially enhanced (8-66%) in high RH-grown plants, indicating a wide variation in high RH tolerance. High RH mainly decreased plant water loss during the light......Plants grown at high relative air humidity (RH) often show disturbed water relations due to less responsive stomata. The attenuation of stomatal responsiveness as a result of high RH during leaf expansion depends on the cultivar. We hypothesized that tolerant cultivars to high RH experience a lower...... decline in plant transpiration by high RH, and that the variation in plant transpiration rate can be reflected by differences in leaf temperature (Tleaf). Plant leaf area, stomatal responsiveness to desiccation, together with plant transpiration and leaf temperature at growth conditions were analyzed...

  11. Interferon-γ activates expression of p15 and p16 regardless of 9p21.3 coronary artery disease risk genotype.

    Science.gov (United States)

    Almontashiri, Naif A M; Fan, Meng; Cheng, Brian L M; Chen, Hsiao-Huei; Roberts, Robert; Stewart, Alexandre F R

    2013-01-15

    Because post-transcriptional mechanisms modulate levels of p16 (encoded by CDKN2A) and p15 (encoded by CDKN2B), we tested whether interferon-γ regulates the expression of these proteins and the effect of the 9p21 genotype. The mechanism whereby the common variant at chromosome 9p21.3 confers risk for coronary artery disease (CAD) remains uncertain. A recent report proposed that 9p21.3 confers differential activation of adjacent genes in response to interferon-γ, and reported that mRNA levels of CDKN2B are reduced in response to interferon-γ. Human umbilical vein endothelial cells (HUVECs), aortic smooth muscle cells, HeLa cells, HEK293 cells, and 16 human lymphoblastoid cell lines, all genotyped for the 9p21.3 locus, were treated with interferon-γ and analyzed by immunoblot. In all cells tested--except HUVECs where expression was not modulated by interferon-γ--regardless of 9p21.3 genotype, interferon-γ increased the expression of p16 and p15. Northern blot analysis confirmed that interferon-γ has little effect on mRNA levels of CDKN2A and CDKN2B. The 9p21.3 risk genotype does not affect the activation of cyclin-dependent kinase inhibitors p15 and p16 by interferon-γ. Thus, another mechanism is likely to account for the CAD risk associated with this locus. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  12. Impact of Genetic Polymorphisms on the Smoking-related Risk of Periodontal Disease: the Population-based Study SHIP

    Directory of Open Access Journals (Sweden)

    Meisel P

    2003-09-01

    Full Text Available Abstract Periodontitis is a bacterial inflammatory disease leading to attachment loss with the consequence of tooth loss. There exists a multifactorial risk pattern including bacterial challenge, smoking, age, sex, diabetes, socio-economic and genetic factors. Smoking has the highest impact on the course of the disease modulated by all the other factors. Here, we report the relationship between smoking and the polymorphisms of genetic polymorphisms inflicted in the pathogenesis. In a randomly selected population-based study, 1083 subjects were typed for the polymorphisms of the IL-1 genotype, Fcγ RIIIb receptor gene, myeloperoxidase and N-acetyltransferase (NAT2 and related to their periodontal state. Smoking behavior was assessed including present and past quality and quantity of smoking. There is a significant dose-effect relationship between the exposure to tobacco smoke and the extent of periodontal disease assessed as attachment loss and tooth loss. Moreover, there are gene-environmental interactions as subjects bearing variant genotypes show an enhanced smoking-associated risk of the disease modulated by these genotypes. In non-smokers, the impact of these genetic polymorphisms is mostly negligible. This study provides support for the hypothesis that subjects bearing genetic variants of polymorphically expressed phenotypes are at an increased risk of periodontitis when smoking. Mostly, this may be accomplished via the influence of smoking-related impairment on defense mechanisms rather than on the pathogenic pathways.

  13. Impact of Genetic Polymorphisms on the Smoking-related Risk of Periodontal Disease: the Population-based Study SHIP

    Directory of Open Access Journals (Sweden)

    Schwahn C

    2003-09-01

    Full Text Available Abstract Periodontitis is a bacterial inflammatory disease leading to attachment loss with the consequence of tooth loss. There exists a multifactorial risk pattern including bacterial challenge, smoking, age, sex, diabetes, socio-economic and genetic factors. Smoking has the highest impact on the course of the disease modulated by all the other factors. Here, we report the relationship between smoking and the polymorphisms of genetic polymorphisms inflicted in the pathogenesis. In a randomly selected population-based study, 1083 subjects were typed for the polymorphisms of the IL-1 genotype, Fcγ RIIIb receptor gene, myeloperoxidase and N-acetyltransferase (NAT2 and related to their periodontal state. Smoking behavior was assessed including present and past quality and quantity of smoking. There is a significant dose-effect relationship between the exposure to tobacco smoke and the extent of periodontal disease assessed as attachment loss and tooth loss. Moreover, there are gene-environmental interactions as subjects bearing variant genotypes show an enhanced smoking-associated risk of the disease modulated by these genotypes. In non-smokers, the impact of these genetic polymorphisms is mostly negligible. This study provides support for the hypothesis that subjects bearing genetic variants of polymorphically expressed phenotypes are at an increased risk of periodontitis when smoking. Mostly, this may be accomplished via the influence of smoking-related impairment on defense mechanisms rather than on the pathogenic pathways.

  14. Genotypic diversity and phenotypic traits of Streptococcus mutans isolates and their relation to severity of early childhood caries.

    Science.gov (United States)

    Valdez, Remberto Marcelo Argandoña; Duque, Cristiane; Caiaffa, Karina Sampaio; Dos Santos, Vanessa Rodrigues; Loesch, Maria Luiza de Aguiar; Colombo, Natalia Helena; Arthur, Rodrigo Alex; Negrini, Thais de Cássia; Boriollo, Marcelo Fabiano Gomes; Delbem, Alberto Carlos Botazzo

    2017-07-14

    Early childhood caries (ECC) is an aggressive condition that can affect teeth of young children. This study aimed to evaluate genotypic diversity and phenotypic traits of S. mutans isolated from dental biofilms of children with different caries status in comparison with caries free (CF) children. Streptococcus mutans strains were isolated from supragingival biofilm samples of CF, ECC and severe-ECC (S-ECC) children and genotyped by arbitrary-primer polymerase chain reaction - AP-PCR. S. mutans genotypes were tested for their ability to reduce the suspension pH through glycolysis, to tolerate extreme acid challenge and by their ability to form biofilm. Response variables were analyzed by ANOVA/Tukey or Kruskal-Wallis/Mann-Whitney tests at a 5% of significance. There was an increase in the prevalence of Streptococcus mutans in biofilms with the severity of dental caries. No differences in genotypic diversity and in acidogenicity of genotypes were found among CF, ECC and S-ECC children. S mutans strains with genotypes more characteristic for ECC and S-ECC children formed more biofilms than those identified in CF children. The strains isolated from S-ECC children were highly acid tolerant. Although S. mutans genotypic diversity was similar among the groups of children, phenotypic traits of S. mutans, especially the acid tolerance response, could explain the severity of early childhood caries.

  15. Evaluation of energy related risk acceptance (APHA energy task force)

    Energy Technology Data Exchange (ETDEWEB)

    Hull, A.P.

    1977-01-01

    Living in a technological society with large energy requirements involves a number of related actities with attendant health risks, both to the working and to the general public. Therefore, the formulation of some general principles for risk acceptance is necessary. In addition to maximizing benefits and minimizing risk, relevant considerations must be made about the perception of risk as voluntary or involuntary, the number of persons collectively at risk at any one occasion, and the extent to which a risk is a familiar one. With regard to a given benefit, such as a given amount of energy, comparisons of the risks of alternate modes of production may be utilized. However, cost-benefit consideration is essential to the amelioration of current or prospective risks. This is unusual, since it is based on some estimate of the monetary value per premature death averted. It is proposed that increased longevity would be a more satisfactory measure. On a societal basis, large expenditures for additional energy-related pollution control do not appear justifiable since much larger, nonenergy-related health risks are relatively underaddressed. Knowledgeable health professionals could benefit the public by imparting authoritative information in this area.

  16. Polysaccharide biosynthesis-related genes explain phenotype-genotype correlation of Microcystis colonies in Meiliang Bay of Lake Taihu, China

    Science.gov (United States)

    Xu, Shutu; Sun, Qianqian; Zhou, Xiaohua; Tan, Xiao; Xiao, Man; Zhu, Wei; Li, Ming

    2016-01-01

    The 16S rDNA, 16S-23S rDNA-ITS, cpcBA-IGS, mcy gene and several polysaccharide biosynthesis-related genes (epsL and TagH) were analyzed along with the identification of the morphology of Microcystis colonies collected in Lake Taihu in 2014. M. wesenbergii colonies could be distinguished directly from other colonies using espL. TagH divided all of the samples into two clusters but failed to distinguish different phenotypes. Our results indicated that neither morphology nor molecular tools including 16S rDNA, 16S-23S ITS and cpcBA-IGS could distinguish toxic and non-toxic species among the identified Microcystis species. No obvious relationship was detected between the phenotypes of Microcystis and their genotypes using 16S, 16S-23S and cpcBA-IGS, but polysaccharide biosynthesis-related genes may distinguish the Microcystis phenotypes. Furthermore, the sequences of the polysaccharide biosynthesis-related genes (espL and TagH) extracted from Microcystis scums collected throughout 2015 was analyzed. Samples dominated by M. ichthyoblabe (60–100%) and M. wesenbergii (60–100%) were divided into different clade by both espL and TagH, respectively. Therefore, it was confirmed that M. wesenbergii and M. ichthyoblabe could be distinguished by the polysaccharide biosynthesis-related genes (espL and TagH). This study is of great significance in filling the gap between classification of molecular biology and the morphological taxonomy of Microcystis. PMID:27752091

  17. Varied definitions of risk related to sensation seeking trait

    Energy Technology Data Exchange (ETDEWEB)

    Daastoel, P.Oe.U.; Drottz-Sjoeberg, B.M. [Norwegian Univ. of Science and Technology, Trondheim (Norway). Dept. of Psychology

    1999-12-01

    This pilot study is based on the assumption and the knowledge that previous results show that the normal use of the word risk varies across subjects. The risk definitions the subjects use have also been shown to be related to various educational interests. A related field of research has developed measures for Sensation Seeking personality trait, with four facets. Three independent groups of first year psychology students reported their normal definition of the word risk using one of three measurement formats. The results showed, e.g. that the typical open-ended response to the personal definition of risk was danger. Subjects who defined risk as the combination of probability and consequences tended to score higher on the total Sensation Seeking Scale, as compared to those defining risk as the probability of an event.

  18. High-risk HPV genotypes and P16INK4a expression in a cohort of head and neck squamous cell carcinoma patients in Singapore.

    Science.gov (United States)

    Tan, Louise Soo Yee; Fredrik, Petersson; Ker, Liang; Yu, Feng Gang; Wang, De Yun; Goh, Boon Cher; Loh, Kwok Seng; Lim, Chwee Ming

    2016-12-27

    Human papillomavirus (HPV), especially HPV16 genotype, is associated with oropharyngeal squamous cell carcinoma (OPSCC). We aim to determine the prevalence and characterize the high-risk (HR)-HPV genotypes in head and neck SCC (HNSCC) in a South-East Asian multi-ethnic society in Singapore and examine its prognostic significance.159 HNSCC archival tissue samples were retrieved and tumour DNA was screened for 18 HR-HPV genotypes using a PCR-based assay (Qiagen, digene HPV genotyping RH test). P16 protein overexpression was identified using immunohistochemistry (IHC). Statistical correlation between clinical outcomes were performed between HPV-positive and negative HNSCC patients.Six HR-HPVs (HPV16, 18, 31, 45, 56, 68) were detected in 90.6% of HNSCC; and 79.9% had multiple HPV genotypes detected. HPV31 and HPV45 were the most prevalent (79.2% and 87.4%, respectively); and HPV16 was predominantly found in OPSCC (p HPV-DNA PCR assay yielded a high sensitivity (96%) but low specificity (11%) when compared to p16 immunohistochemistry as the reference standard.P16-positive HNSCC was predominantly observed in OPSCC (73.7%; p = 0.005); and p16-positive OPSCC exhibited improved overall survival compared to p16-negative OPSCC (p = 0.022). Similarly, smoking and alcohol consumption were poor prognostic factors of overall survival (p = 0.007; p = 0.01) in OPSCC patients.HR-HPVs were identified in 90.6% of HNSCC patients using the HPV-DNA PCR assay. This test had a poor specificity when compared to p16 IHC; making it an unreliable detection technique in selecting patients for radiation dose de-escalation treatment protocol. P16-positive tumor was predominantly found in the oropharynx these patients demonstrated better overall survival than those with p16-negative OPSCC.

  19. Simultaneous genotyping of single-nucleotide polymorphisms in alcoholism-related genes using duplex and triplex allele-specific PCR with two-step thermal cycles.

    Science.gov (United States)

    Shirasu, Naoto; Kuroki, Masahide

    2014-01-01

    We developed a time- and cost-effective multiplex allele-specific polymerase chain reaction (AS-PCR) method based on the two-step PCR thermal cycles for genotyping single-nucleotide polymorphisms in three alcoholism-related genes: alcohol dehydrogenase 1B, aldehyde dehydrogenase 2 and μ-opioid receptor. Applying MightyAmp(®) DNA polymerase with optimized AS-primers and PCR conditions enabled us to achieve effective and selective amplification of the target alleles from alkaline lysates of a human hair root, and simultaneously to determine the genotypes within less than 1.5 h using minimal lab equipment.

  20. The low-template-DNA (stochastic) threshold--its determination relative to risk analysis for national DNA databases.

    Science.gov (United States)

    Gill, Peter; Puch-Solis, Roberto; Curran, James

    2009-03-01

    Although the low-template or stochastic threshold is in widespread use and is typically set to 150-200 rfu peak height, there has been no consideration on its determination and meaning. In this paper we propose a definition that is based upon the specific risk of wrongful designation of a heterozygous genotype as a homozygote which could lead to a false exclusion. Conversely, it is possible that a homozygote {a,a} could be designated as {a,F} where 'F' is a 'wild card', and this could lead to increased risk of false inclusion. To determine these risk levels, we analysed an experimental dataset that exhibited extreme drop-out using logistic regression. The derived probabilities are employed in a graphical model to determine the relative risks of wrongful designations that may cause false inclusions and exclusions. The methods described in this paper provide a preliminary solution of risk evaluation for any DNA process that employs a stochastic threshold.

  1. Genotype status of the dopamine-related catechol-O-methyltransferase (COMT) gene corresponds with desirability of “unhealthy” foods

    NARCIS (Netherlands)

    Wallace, D.L.; Aarts, E.; d'Oleire Uquillas, F.; Dang, L.C.; Greer, S.M.; Jagust, W.J.; D'Esposito, M.

    2015-01-01

    The role of dopamine is extensively documented in weight regulation and food intake in both animal models and humans. Yet the role of dopamine has not been well studied in individual differences for food desirability. Genotype status of the dopamine-related catechol-O-methyltransferase (COMT) gene h

  2. Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7)

    DEFF Research Database (Denmark)

    Husemoen, L L N; Thomsen, T F; Fenger, M;

    2004-01-01

    OBJECTIVE: To examine the associations between various lifestyle factors--smoking habits, physical activity, dietary habits, coffee, tea, and alcohol consumption--and homocysteine (tHcy) in relation to MTHFR(C677T) genotype. DESIGN: Cross-sectional population-based study. SETTING: Residents...

  3. Personality, risk cognitions and motivation related to demand of risk mitigation in transport among Norwegians

    OpenAIRE

    Nordfjærn, Trond; Rundmo, Torbjørn

    2014-01-01

    There is insufficient knowledge regarding the role of personality traits, transport-related risk cognitions and safety motivation for demand for transport risk mitigation. The aim of this study is to test a model aimed to predict public demand for transport risk mitigation by these psychological risk constructs. A mailed self-completion questionnaire survey was conducted in a random sample of the Norwegian population aged 18–65 years obtained from the Norwegian population registry (n...

  4. Genotype by environment interaction for activity-based estrus traits in relation to production level for Danish Holstein.

    Science.gov (United States)

    Ismael, Ahmed; Strandberg, Erling; Berglund, Britt; Kargo, Morten; Fogh, Anders; Løvendahl, Peter

    2016-12-01

    , the same trend was observed when the data were analyzed using MT where the genetic correlation between CFHA and ECM70 in the low production environment was 0.29 compared with -0.13 in the high production environment, but these estimates had large standard errors. In conclusion, regardless of the trait used, in relation to average herd ECM70 production, the results indicated no clear evidence of strong genotype by environment interaction that would cause significant re-ranking of sires between low and high production environments. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7)

    DEFF Research Database (Denmark)

    Husemoen, L L N; Thomsen, T F; Fenger, M

    2004-01-01

    a Fluorescent Polarization Immuno Assay. MTHFR-genotype was determined by PCR and RFLP analysis. Information about lifestyle factors was obtained from a self-administered questionnaire. RESULTS: Daily smoking, less healthy dietary habits, and coffee drinking were associated with elevated tHcy concentrations......OBJECTIVE: To examine the associations between various lifestyle factors--smoking habits, physical activity, dietary habits, coffee, tea, and alcohol consumption--and homocysteine (tHcy) in relation to MTHFR(C677T) genotype. DESIGN: Cross-sectional population-based study. SETTING: Residents....... The effect of smoking was more pronounced in persons with the TT genotype and in women. The effect of beer consumption was more pronounced at younger than at older ages. CONCLUSIONS: Smoking status, dietary habits, coffee intake, wine, and beer consumption were major lifestyle determinants of tHcy. Changes...

  6. Effect of Se application on photosynthesis, osmolytes and water relations in two durum wheat (Triticum durum L. genotypes under drought stress

    Directory of Open Access Journals (Sweden)

    Roghieh HAJIBOLAND

    2015-12-01

    Full Text Available Effect of Se (as Na2SeO4 at final concentration of 10 µg l-1 was studied in two durum wheat (Triticum durum L. genotypes in perlite under drought conditions. Se treatment increased slightly biomass of both genotypes under drought but not under control conditions. Photosynthetic rate was depressed by drought while increased by Se treatments in both genotypes up to 2.3 fold. However, transpirational water loss was also enhanced in Se-treated plants under both well-watered and drought conditions. Se application resulted in higher concentrations of soluble proteins and free α-amino acids under drought conditions, but not proline. Our results indicated that Se application improves some physiological parameters such as photosynthesis, accumulation of osmolyes and water use efficiency but did not change significantly plants biomass or water relation parameters.

  7. Assessment of the photosynthesis-related traits and high temperature resistance in tetraploid wheat (Triticum L. genotypes

    Directory of Open Access Journals (Sweden)

    Katarina OLSOVSKA

    2013-06-01

    Full Text Available The collection of 10 parental lines of tetraploid wheat genotypes with various origin was cultivated in growth chamber. Leaf and growth traits such as assimilation pigments content, dry mass and leaf area of plants were measured. The genotype differences were recognized by chlorophyll a fluorescence fast kinetics method applied on penultimate young wheat leaves. Consequently, heat stress susceptibility based on the exposure of whole plants in pots to air temperature of 42oC for 6 hours was measured, too. Rapid chlorophyll a fluorescence kinetics method gave us better knowledge about differences among tetraploid wheat genotypes collection comparing to classic assimilation pigments analyse. Genotypes with higher content of pigments did not always exhibit good resistance against heat stress. Using the chlorophyll fluorescence parameters, the rating of genotypes based on photosynthetic performance as well as photosystem II (PSII thermostability was done. We identified the genotypes TRG7 (Triticum turgidum subsp. turgidum, PI 384230, Ethiopia and RONCAL (Triticum turgidum subsp. dicoccon, TRI 17700, Spain as the perspective donors of genes for better thermostability of photosynthetic apparatus in changed climate conditions and material into wheat efficiency breeding programs.

  8. Sequencing of Gag/Env association with HIV genotyping resolution and HIV-related epidemiologic studies of HIV in China.

    Science.gov (United States)

    Ren, L; Wang, H W; Xu, Y; Feng, Y; Zhang, H F; Wang, K H

    2016-10-24

    HIV genotyping has led to conflicting results between laboratories. Therefore, identifying the most accurate gene combinations to sequence remains a priority. Datasets of Chinese HIV subtypes based on several markers and deposited in PubMed, Metstr, CNKI, and VIP databases between 2000 and 2015 were studied. In total, 9177 cases of amplification-positive samples from 26 provinces of China were collected and used to classify HIV subtypes based on eight individual genes or a combination thereof. CRF01_AE, CRF07_BC, CRF08_BC and B were the prevalent HIV subtypes in China, accounting for 84.07% of all genotypes. Gag/Env sequencing classified a greater number of HIV subtypes compared to other genes or combination of gene fragments. The geographical distribution of Gag and Gag/Env genotypes was similar to that observed with all genetic markers. Further principal component analysis showed a significantly different geographical distribution pattern of HIV in China for HIV genotypes detected with Gag/Env, which was in line with the distribution of all HIV genotypes in China. Gag/Env sequences had the highest diversity of the eight markers studied, followed by Gag and Gag/Pol/Env; Pol/Env polymorphisms were the least divergent. Gag/Env can serve as a high-resolution marker for HIV genotyping.

  9. Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study.

    Science.gov (United States)

    Cadenas-Benitez, N M; Yanes-Sosa, F; Gonzalez-Meneses, A; Cerrillos, L; Acosta, D; Praena-Fernandez, J M; Neth, O; Gomez de Terreros, I; Ybot-González, P

    2014-03-26

    Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

  10. Risk of bleeding related to antithrombotic treatment in cardiovascular disease

    DEFF Research Database (Denmark)

    Sørensen, Rikke; Olesen, Jonas B; Charlot, Mette;

    2012-01-01

    Antithrombotic therapy is a cornerstone of treatment in patients with cardiovascular disease with bleeding being the most feared complication. This review describes the risk of bleeding related to different combinations of antithrombotic drugs used for cardiovascular disease: acute coronary...

  11. CKD Increases the Risk of Age-Related Macular Degeneration

    OpenAIRE

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-01-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerul...

  12. MTHFR C677T genotype and cardiovascular risk in a general population without mandatory folic acid fortification

    DEFF Research Database (Denmark)

    Husemoen, Lise Lotte N; Skaaby, Tea; Jørgensen, Torben

    2014-01-01

    Meta-analyses have suggested an effect of MTHFR C677T genotype (rs1801133), a proxy for blood total homocysteine, on cardiovascular disease (CVD) in populations with low population dietary folate. The aim was to examine the association and effect modification by serum folate and vitamin B12 level...

  13. Risk assessment and communication tools for genotype associations with multifactorial phenotypes: the concept of "edge effect" and cultivating an ethical bridge between omics innovations and society.

    Science.gov (United States)

    Ozdemir, Vural; Suarez-Kurtz, Guilherme; Stenne, Raphaëlle; Somogyi, Andrew A; Someya, Toshiyuki; Kayaalp, S Oğuz; Kolker, Eugene

    2009-02-01

    Applications of omics technologies in the postgenomics era swiftly expanded from rare monogenic disorders to multifactorial common complex diseases, pharmacogenomics, and personalized medicine. Already, there are signposts indicative of further omics technology investment in nutritional sciences (nutrigenomics), environmental health/ecology (ecogenomics), and agriculture (agrigenomics). Genotype-phenotype association studies are a centerpiece of translational research in omics science. Yet scientific and ethical standards and ways to assess and communicate risk information obtained from association studies have been neglected to date. This is a significant gap because association studies decisively influence which genetic loci become genetic tests in the clinic or products in the genetic test marketplace. A growing challenge concerns the interpretation of large overlap typically observed in distribution of quantitative traits in a genetic association study with a polygenic/multifactorial phenotype. To remedy the shortage of risk assessment and communication tools for association studies, this paper presents the concept of edge effect. That is, the shift in population edges of a multifactorial quantitative phenotype is a more sensitive measure (than population averages) to gauge the population level impact and by extension, policy significance of an omics marker. Empirical application of the edge effect concept is illustrated using an original analysis of warfarin pharmacogenomics and the VKORC1 genetic variation in a Brazilian population sample. These edge effect analyses are examined in relation to regulatory guidance development for association studies. We explain that omics science transcends the conventional laboratory bench space and includes a highly heterogeneous cast of stakeholders in society who have a plurality of interests that are often in conflict. Hence, communication of risk information in diagnostic medicine also demands attention to processes

  14. Risk communication related to animal products derived from biotechnology.

    Science.gov (United States)

    McCrea, D

    2005-04-01

    Previous chapters of this review have dealt with the key considerations related to the application of biotechnology in veterinary science and animal production. This article explores the theory and practice of risk communication and sets out the basic principles for good risk communication when dealing with new technologies, uncertainty, and cautious and sceptical consumers. After failure to communicate with consumers and stakeholders about the risk to human health from bovine spongiform encephalopathy (BSE) in the 1990s, Government Agencies in the United Kingdom have made significant improvements in risk communication. The official inquiry that followed the BSE crisis concluded that a policy of openness was the correct approach, and this article emphasises the importance of consultation, consistency and transparency. There are, however, many different factors that affect public perception of risk (religious, political, social, cultural, etc.) and developing effective risk communication strategies must take all of these complex issues into consideration.

  15. Newly identified genetic risk variants for celiac disease related to the immune response

    NARCIS (Netherlands)

    Hunt, Karen A.; Zhernakova, Alexandra; Turner, Graham; Heap, Graham A. R.; Franke, Lude; Bruinenberg, Marcel; Romanos, Jihane; Dinesen, Lotte C.; Ryan, Anthony W.; Panesar, Davinder; Gwilliam, Rhian; Takeuchi, Fumihiko; McLaren, William M.; Holmes, Geoffrey K. T.; Howdle, Peter D.; Walters, Julian R. F.; Sanders, David S.; Playford, Raymond J.; Trynka, Gosia; Mulder, Chris J. J.; Mearin, M. Luisa; Verbeek, Wieke H. M.; Trimble, Valerie; Stevens, Fiona M.; O'Morain, Colm; Kennedy, Nicholas P.; Kelleher, Dermot; Pennington, Daniel J.; Strachan, David P.; McArdle, Wendy L.; Mein, Charles A.; Wapenaar, Martin C.; Deloukas, Panos; McGinnis, Ralph; McManus, Ross; Wijmenga, Cisca; van Heel, David A.

    2008-01-01

    Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including t

  16. Cryptosporidium and Giardia in Danish organic pig farms: Seasonal and age-related variation in prevalence, infection intensity and species/genotypes.

    Science.gov (United States)

    Petersen, Heidi H; Jianmin, Wang; Katakam, Kiran K; Mejer, Helena; Thamsborg, Stig M; Dalsgaard, Anders; Olsen, Annette; Enemark, Heidi L

    2015-11-30

    Although pigs are commonly infected with Cryptosporidium spp. and Giardia duodenalis, including potentially zoonotic species or genotypes, little is known about age-related infection levels, seasonal differences and genetic variation in naturally infected pigs raised in organic management systems. Therefore, the current study was conducted to assess seasonal and age-related variations in prevalence and infection intensity of Cryptosporidium and Giardia, evaluate zoonotic potential and uncover correlations between species/genotypes, infection intensity and faecal consistency. Shedding of oocysts and cysts ((oo-)cysts) was monitored at quarterly intervals (September 2011-June 2012) in piglets (n = 152), starter pigs (n = 234), fatteners (n = 230) and sows (n = 240) from three organic farms in Denmark. (oo-)Cysts were quantified by immunofluorescence microscopy; and 56/75 subsamples from Cryptosporidium infected pigs were successfully analysed by PCR amplification and partial sequencing of the small subunit (SSU) 18S rRNA and hsp70genes, while 13/67 Giardia subsamples were successfully analysed by amplification and partial sequencing of the 18S rRNA and the gdh genes. Altogether, Cryptosporidium or Giardia infections were observed in 40.9% (350/856) and 14.0% (120/856) of the pigs, respectively, including 8.2% (70/856) infected with both parasites. Prevalence, intensity of infections and presence of Cryptosporidium species varied significantly between age-groups; 53.3% piglets, 72.2% starter pigs, 40.4% fatteners and 2.9% sows were infected with Cryptosporidium, whereas 2.0% piglets, 27.4% starter pigs, 17.8% fatteners and 5.0% sows were infected with Giardia. The overall prevalence was stable throughout the year, except for dual-infections that were more prevalent in September and December (p parasites, and dual-infected pigs tended to excrete lower levels of oocysts compared to pigs harbouring only Cryptosporidium. Likewise, pigs infected with Cryptosporidium

  17. Serum glucose and fructosamine in relation to risk of cancer.

    Directory of Open Access Journals (Sweden)

    Wahyu Wulaningsih

    Full Text Available BACKGROUND: Impaired glucose metabolism has been linked with increased cancer risk, but the association between serum glucose and cancer risk remains unclear. We used repeated measurements of glucose and fructosamine to get more insight into the association between the glucose metabolism and risk of cancer. METHODS: We selected 11,998 persons (>20 years old with four prospectively collected serum glucose and fructosamine measurements from the Apolipoprotein Mortality Risk (AMORIS study. Multivariate Cox proportional hazards regression was used to assess standardized log of overall mean glucose and fructosamine in relation to cancer risk. Similar analyses were performed for tertiles of glucose and fructosamine and for different types of cancer. RESULTS: A positive trend was observed between standardized log overall mean glucose and overall cancer risk (HR= 1.08; 95% CI: 1.02-1.14. Including standardized log fructosamine in the model resulted in a stronger association between glucose and cancer risk and aninverse association between fructosamine and cancer risk (HR = 1.17; 95% CI: 1.08-1.26 and HR: 0.89; 95% CI: 0.82-0.96, respectively. Cancer risks were highest among those in the highest tertile of glucose and lowest tertile of fructosamine. Similar findings were observed for prostate, lung, and colorectal cancer while none observed for breast cancer. CONCLUSION: The contrasting effect between glucose, fructosamine, and cancer risk suggests the existence of distinct groups among those with impaired glucose metabolism, resulting in different cancer risks based on individual metabolic profiles. Further studies are needed to clarify whether glucose is a proxy of other lifestyle-related or metabolic factors.

  18. Serum glucose and fructosamine in relation to risk of cancer.

    Science.gov (United States)

    Wulaningsih, Wahyu; Holmberg, Lars; Garmo, Hans; Zethelius, Björn; Wigertz, Annette; Carroll, Paul; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Jungner, Ingmar; Van Hemelrijck, Mieke

    2013-01-01

    Impaired glucose metabolism has been linked with increased cancer risk, but the association between serum glucose and cancer risk remains unclear. We used repeated measurements of glucose and fructosamine to get more insight into the association between the glucose metabolism and risk of cancer. We selected 11,998 persons (>20 years old) with four prospectively collected serum glucose and fructosamine measurements from the Apolipoprotein Mortality Risk (AMORIS) study. Multivariate Cox proportional hazards regression was used to assess standardized log of overall mean glucose and fructosamine in relation to cancer risk. Similar analyses were performed for tertiles of glucose and fructosamine and for different types of cancer. A positive trend was observed between standardized log overall mean glucose and overall cancer risk (HR= 1.08; 95% CI: 1.02-1.14). Including standardized log fructosamine in the model resulted in a stronger association between glucose and cancer risk and aninverse association between fructosamine and cancer risk (HR = 1.17; 95% CI: 1.08-1.26 and HR: 0.89; 95% CI: 0.82-0.96, respectively). Cancer risks were highest among those in the highest tertile of glucose and lowest tertile of fructosamine. Similar findings were observed for prostate, lung, and colorectal cancer while none observed for breast cancer. The contrasting effect between glucose, fructosamine, and cancer risk suggests the existence of distinct groups among those with impaired glucose metabolism, resulting in different cancer risks based on individual metabolic profiles. Further studies are needed to clarify whether glucose is a proxy of other lifestyle-related or metabolic factors.

  19. APOE genotype-function relationship: evidence of -491 A/T promoter polymorphism modifying transcription control but not type 2 diabetes risk.

    Directory of Open Access Journals (Sweden)

    Hua Geng

    Full Text Available BACKGROUND: The apolipoprotein E gene (APOE coding polymorphism modifies the risks of Alzheimer's disease, type 2 diabetes, and coronary heart disease. Aside from the coding variants, single nucleotide polymorphism (SNP of the APOE promoter has also been shown to modify the risk of Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigate the genotype-function relationship of APOE promoter polymorphism at molecular level and at physiological level: i.e., in transcription control of the gene and in the risk of type 2 diabetes. In molecular studies, the effect of the APOE -491A/T (rs449647 polymorphism on gene transcription was accessed by dual-luciferase reporter gene assays. The -491 A to T substitution decreased the activity (p<0.05 of the cloned APOE promoter (-1017 to +406. Using the -501 to -481 nucleotide sequence of the APOE promoter as a 'bait' to screen the human brain cDNA library by yeast one-hybrid system yielded ATF4, an endoplasmic reticulum stress response gene, as one of the interacting factors. Electrophoretic-mobility-shift assays (EMSA and chromatin immuno-precipitation (ChIP analyses further substantiated the physical interaction between ATF4 and the APOE promoter. Over-expression of ATF4 stimulated APOE expression whereas siRNA against ATF4 suppressed the expression of the gene. However, interaction between APOE promoter and ATF4 was not -491A/T-specific. At physiological level, the genotype-function relationship of APOE promoter polymorphism was studied in type 2 diabetes. In 630 cases and 595 controls, three APOE promoter SNPs -491A/T, -219G/T (rs405509, and +113G/C (rs440446 were genotyped and tested for association with type 2 diabetes in Hong Kong Chinese. No SNP or haplotype association with type 2 diabetes was detected. CONCLUSIONS/SIGNIFICANCE: At molecular level, polymorphism -491A/T and ATF4 elicit independent control of APOE gene expression. At physiological level, no genotype-risk

  20. Level of muscle regeneration in limb-girdle muscular dystrophy type 2I relates to genotype and clinical severity

    Directory of Open Access Journals (Sweden)

    Krag Thomas O

    2011-10-01

    Full Text Available Abstract Background The balance between muscle regeneration and ongoing degeneration is a relationship that greatly influences the progression of muscular dystrophy. Numerous factors may influence the muscle regeneration, but more information about the relationship between genotype, clinical severity and the ability to regenerate is needed. Methods Muscle biopsies were obtained from the tibialis anterior muscle, and frozen sections were stained for general histopathological and immunohistological evaluation. Differences between groups were considered statistical significant at P t-test. Results We found that all patients with limb-girdle muscular dystrophy type 2I (LGMD2I had a large number of internally nucleated fibers, a sign of previous regeneration. The level of expression of muscle-specific developmental proteins, such as neonatal myosin heavy chain (nMHC and myogenin, was related to the clinical severity. Additionally, we found that the majority of nMHC-positive fibers did not stain positively for utrophin in patients who were compound heterozygous for the L276I mutation, suggesting that the predominant form of regeneration in these patients is fiber repair rather than formation of new fibers. Double staining showed that many smaller nMHC-positive fibers were positive for antibodies against the glycosylation on α-dystroglycan, suggesting that such glycosylation may be a result of muscle regeneration. Conclusion Severely affected patients with LGMD2I have a high level of muscle degeneration, which leads to a high rate of regeneration, but this is insufficient to change the imbalance between degeneration and regeneration, ultimately leading to progressive muscle wasting. Detailed information regarding the level and rate of muscle regeneration and potential obstructions of the regenerative pathway should be of use for future therapies involving satellite-cell activation.

  1. Prevalence of at-risk genotypes for genotoxic effects decreases with age in a randomly selected population in Flanders: a cross sectional study

    Directory of Open Access Journals (Sweden)

    van Delft Joost HM

    2011-10-01

    Full Text Available Abstract Background We hypothesized that in Flanders (Belgium, the prevalence of at-risk genotypes for genotoxic effects decreases with age due to morbidity and mortality resulting from chronic diseases. Rather than polymorphisms in single genes, the interaction of multiple genetic polymorphisms in low penetrance genes involved in genotoxic effects might be of relevance. Methods Genotyping was performed on 399 randomly selected adults (aged 50-65 and on 442 randomly selected adolescents. Based on their involvement in processes relevant to genotoxicity, 28 low penetrance polymorphisms affecting the phenotype in 19 genes were selected (xenobiotic metabolism, oxidative stress defense and DNA repair, respectively 13, 6 and 9 polymorphisms. Polymorphisms which, based on available literature, could not clearly be categorized a priori as leading to an 'increased risk' or a 'protective effect' were excluded. Results The mean number of risk alleles for all investigated polymorphisms was found to be lower in the 'elderly' (17.0 ± 2.9 than the 'adolescent' (17.6 ± 3.1 subpopulation (P = 0.002. These results were not affected by gender nor smoking. The prevalence of a high (> 17 = median number of risk alleles was less frequent in the 'elderly' (40.6% than the 'adolescent' (51.4% subpopulation (P = 0.002. In particular for phase II enzymes, the mean number of risk alleles was lower in the 'elderly' (4.3 ± 1.6 than the 'adolescent' age group (4.8 ± 1.9 P 4 = median number of risk alleles was less frequent in the 'elderly' (41.3% than the adolescent subpopulation (56.3%, P 8 = median number of risk alleles for DNA repair enzyme-coding genes was lower in the 'elderly' (37,3% than the 'adolescent' subpopulation (45.6%, P = 0.017. Conclusions These observations are consistent with the hypothesis that, in Flanders, the prevalence of at-risk alleles in genes involved in genotoxic effects decreases with age, suggesting that persons carrying a higher number of

  2. Methylenetetrahydrofolate Reductase Genotypes, Dietary Habits and Susceptibility to Stomach Cancer

    Institute of Scientific and Technical Information of China (English)

    ChangmingGao; TakezakiToshiro; JianzhongWu; JianhuoDing; YantingLiu; SupingLi; PingSu; XuHu; TianliongXu; HamajimaNobuyuki; TajimaKazuo

    2004-01-01

    OBJECTIVE To study the relation among methylenetetrahydrofolate reductase (MTHFR) C677T genotypes, dietary habits and the risk of stomach cancer (SC).METHODS A case-control study was conducted with 107 cases of SC and 200 population-based controls in Chuzhou district, Huaian, Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects..MTHFR genotypes were detected by PCR-RFLP. RESULTS (1) The prevalence of the MTHFR C/T or T/T genotypes was found to be significantly different between controls (68.5%) and SC cases (79.4%,P=0.0416), the increased risk had an adjusted OR of 1.79 (95%C1:1.01-3.19). (2) Among subjects who had a low intake of garlic or Chinese onion, MTHFR C/T or T/T genotypes significantly increased the risk of developing SC. Among non-tea drinkers or among subjects who had a frequent intakeof meat, the carriers of the MTHFR C/T or T/T genotypes had a higher risk of SC than individuals with the C/C type MTHFR. CONCLUSION The polymorphism of MTHFR C677T was associated with increased risk of developing SC, and that individuals with differing genotypes may have different susceptibilities to SC, based on their exposure level to environmental factors.

  3. Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy

    Directory of Open Access Journals (Sweden)

    Aleeca F. Bell

    2015-07-01

    Full Text Available Postpartum depression (PPD affects up to 19% of women, negatively impacting maternal and infant health. Reductions in plasma oxytocin levels have been associated with PPD and heritability studies have established a genetic contribution. Epigenetic regulation of the oxytocin receptor gene (OXTR has been demonstrated and we hypothesized that individual epigenetic variability at OXTR may impact the development of PPD and that such variability may be central to predicting risk. This case-control study is nested within the Avon Longitudinal Study of Parents and Children and included 269 cases with PPD and 276 controls matched on age group, parity, and presence or absence of depressive symptoms in pregnancy as assessed by the Edinburgh Postnatal Depression Scale. OXTR DNA methylation (CpG site -934 and genotype (rs53576 and rs2254298 were assayed from DNA extracted from blood collected during pregnancy. Conditional logistic regression was used to estimate odds ratios (OR and 95% confidence intervals (CI for the association of elevated symptoms of PPD with genotype, methylation, and their interaction adjusted for psychosocial factors (n=500. There was evidence of an interaction between rs53576 and methylation in the OXTR gene amongst women who did not have depression prenatally but developed PPD (p interaction=0.026, adjusted for covariates, n=257. Those women with GG genotype showed 2.63 greater odds of PPD for every 10% increase in methylation level (95% CI: 1.37, 5.03, whereas methylation was unrelated to PPD amongst A carriers (OR=1.00, 95%CI: 0.58, 1.73. There was no such interaction among women with PPD and prenatal depression. These data indicate that epigenetic variation that decreases expression of OXTR in a susceptible genotype may play a contributory role in the etiology of postpartum depression.

  4. Clinical features of sarcoidosis in relation to HLA distribution and HLA-DRB3 genotyping by PCR-RFLP.

    OpenAIRE

    Ishihara, M; Ishida, T.; Mizuki, N; Inoko, H.; Ando, H; Ohno, S

    1995-01-01

    BACKGROUND--Susceptibility to the development of sarcoidosis has been demonstrated to be associated with HLA-DR5, -DR6, and -DR8 encoded by the DRB1 gene. However, involvement of the DRB3 (HLA-DR52) gene in the development of sarcoidosis remains unclear. METHODS--HLA-DRB3 genotyping was performed using the PCR-RFLP method and the clinical features of the patients with and without the DR3, 5, 6, 8 group antigens were compared. RESULTS--HLA-DRB3 genotyping indicated an association between DRB3*...

  5. Methylenetetrahydrofolate Reductase 677TT Genotype may be Associated with an Increased Lung Cancer Risk in North China: An Updated Meta

    Science.gov (United States)

    Liu, Nan-Bo; Li, Jun; Qi, Jia-Feng; Zhang, Zhen-Zhong; Wu, Xu; Zhang, Jun-Hua

    2014-01-01

    Background Although many epidemiology studies have investigated the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and their associations with lung cancer (LC), definite conclusions cannot be drawn. To clarify the effects of MTHFR polymorphisms on the risk of LC, we performed a meta-analysis in Chinese populations. Material/Methods Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) until 16 February 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. Results A total of 11 studies with 2487 LC cases and 3228 controls were included in this meta-analysis. Overall, no significant association was found between MTHFR C677T polymorphism and LC risk when all studies in Chinese populations were pooled into this meta-analysis. In subgroup analyses stratified by geographical location and source of controls, significantly increased risk was found in North China (T vs. C: OR=1.28, 95% CI: 1.14–1.44; TT vs. CC: OR=1.67, 95% CI: 1.33–2.10; TT + CT vs. CC, OR=1.39, 95% CI=1.15–1.69; TT vs. CC + CT: OR=1.46, 95% CI: 1.03–2.06) and in population-based studies (TT vs. CC: OR=1.37, 95% CI: 1.14–1.65; TT vs. CC + CT: OR=1.25, 95% CI: 1.07–1.45). Conclusions This meta-analysis provides evidence that MTHFR C677T polymorphism may contribute to LC development in North China. Studies with larger sample sizes and wider spectrum of populations are warranted to verify this finding. PMID:25544260

  6. Cryptosporidium and Giardia in Danish organic pig farms: seasonal and age-related variation in prevalence, infection intensity and species/genotypes

    DEFF Research Database (Denmark)

    Petersen, Heidi Huus; Jianmin, Wang; Katakam, Kiran K.

    2015-01-01

    intensity was age-related for both parasites, and dual-infected pigs tended to excrete lower levels of oocysts compared to pigs harbouring only Cryptosporidium. Likewise, pigs infected with C. scrofarum excreted fewer oocysts (mean CPG: 54,848±194,508CI: 9085–118,781) compared......Although pigs are commonly infected with Cryptosporidium spp. and Giardia duodenalis, including potentially zoonotic species or genotypes, little is known about age-related infection levels, seasonal differences and genetic variation in naturally infected pigs raised in organic management systems....... Therefore, the current study was conducted to assess seasonal and age-related variations in prevalence and infection intensity of Cryptosporidium and Giardia, evaluate zoonotic potential and uncover correlations between species/genotypes, infection intensity and faecal consistency. Shedding of oocysts...

  7. Genetic dyslexia risk variant is related to neural connectivity patterns underlying phonological awareness in children.

    Science.gov (United States)

    Skeide, Michael A; Kirsten, Holger; Kraft, Indra; Schaadt, Gesa; Müller, Bent; Neef, Nicole; Brauer, Jens; Wilcke, Arndt; Emmrich, Frank; Boltze, Johannes; Friederici, Angela D

    2015-09-01

    Phonological awareness is the best-validated predictor of reading and spelling skill and therefore highly relevant for developmental dyslexia. Prior imaging genetics studies link several dyslexia risk genes to either brain-functional or brain-structural factors of phonological deficits. However, coherent evidence for genetic associations with both functional and structural neural phenotypes underlying variation in phonological awareness has not yet been provided. Here we demonstrate that rs11100040, a reported modifier of SLC2A3, is related to the functional connectivity of left fronto-temporal phonological processing areas at resting state in a sample of 9- to 12-year-old children. Furthermore, we provide evidence that rs11100040 is related to the fractional anisotropy of the arcuate fasciculus, which forms the structural connection between these areas. This structural connectivity phenotype is associated with phonological awareness, which is in turn associated with the individual retrospective risk scores in an early dyslexia screening as well as to spelling. These results suggest a link between a dyslexia risk genotype and a functional as well as a structural neural phenotype, which is associated with a phonological awareness phenotype. The present study goes beyond previous work by integrating genetic, brain-functional and brain-structural aspects of phonological awareness within a single approach. These combined findings might be another step towards a multimodal biomarker for developmental dyslexia.

  8. [Science, technique, and culture: relations between risk and health practices].

    Science.gov (United States)

    Czeresnia, Dina

    2004-01-01

    This article discusses the cultural consequences of discourses and practices aimed at training subjects for a rational, informed choice in relation to risks, calculated on the basis of scientific knowledge. The epidemiological risk concept is a central element in this process, especially in the context of health practices. The article begins by briefly characterizing the epidemiological risk concept, emphasizing that as an abstract model, it reduces the complexity of the phenomena it studies. Grasping reality through this abstraction generates values and meanings. Canguilhem's reflection on the relations between science, technique, and life is further discussed from the perspective of deepening an understanding of the cultural consequences of this process, contributing to the transformation of classical concepts of individuality, autonomy, and sociability. Such vital themes as individuality, alterity, and the relationship with death are present (albeit disguised) in issues that involve the central nature of risk in the contemporary world.

  9. IGF1 genotype, mean plasma level and breast cancer risk in the Hawaii/Los Angeles multiethnic cohort.

    Science.gov (United States)

    DeLellis, K; Ingles, S; Kolonel, L; McKean-Cowdin, R; Henderson, B; Stanczyk, F; Probst-Hensch, N M

    2003-01-27

    The insulin-like growth factor 1 gene (IGF1) is a strong candidate gene for a breast cancer susceptibility model. We investigated a dinucleotide repeat 969 bp upstream from the transcription start site of the IGF1 gene for possible associations with plasma IGF1 levels and breast cancer risk in a multiethnic group of postmenopausal women. Furthermore, we investigated the relation between race/ethnicity, mean plasma IGF1 levels and breast cancer rates in the Hawaii/Los Angeles Multiethnic Cohort. The mean age-adjusted IGF1 level among Latino-American women, 116 ng ml(-1), was statistically significantly lower than the mean age-adjusted IGF1 levels for each of the three other racial/ethnic groups, African-American, Japanese-American and Non-Latino White women (146, 144 and 145 ng ml(-1), respectively) (PLatino-American women have the lowest breast cancer rates of any racial/ethnic group in the cohort. These results support the investigation of an expansion of the hypothesis for an important role of IGF1 in breast cancer tumorigenesis to different racial/ethnic groups and to postmenopausal women. It is unlikely that any involvement of IGF1 in breast cancer aetiology is mediated by the IGF1 dinucleotide repeat polymorphism, which was not significantly associated with circulating IGF1 levels nor breast cancer risk in this study. Research into relevant determinants of IGF1 levels in the blood must continue.

  10. Vitamin D receptor gene polymorphisms in relation to the risk of colorectal cancer in the Polish population.

    Science.gov (United States)

    Laczmanska, Izabela; Laczmanski, Lukasz; Bebenek, Marek; Karpinski, Pawel; Czemarmazowicz, Halina; Ramsey, David; Milewicz, Andrzej; Sasiadek, Maria M

    2014-12-01

    The protective effect of vitamin D against several cancers including colorectal cancer is modulated by the vitamin D receptor (VDR) and its ligand, the active form of vitamin D. VDR response has been found to play a role in various genes encoding proteins involved in crucial cellular pathways. Single nucleotide polymorphisms (SNPs) of the VDR gene that modulate its activity are located in the promoter region, exons 2-9, and their vicinity and also in the 3'UTR region. Some of them have been previously studied in relation to cancer susceptibility and prognosis. The aim of our study was to investigate four polymorphisms, BsmI, ApaI, TaqI, and FokI, of the VDR gene in Polish patients with sporadic colorectal cancer and to evaluate their association with susceptibility to cancer. We found a significant association between the BsmI genotype and cancer (individuals with the bb genotype are more susceptible to cancer compared to those with other genotypes, p = 0.025, Fisher's exact test for 2 × 2 table). Also, the TT genotype at TaqI and the AA genotype at ApaI are correlated with a higher risk of cancer (p = 0.00071 and p = 1.0 × 10(-5), respectively). We found relatively strong linkage disequilibrium between the TaqI and ApaI loci (T with A and t with a, respectively). Both of these loci are associated with cancer. We do not observe any such association for the FokI polymorphism. In conclusion, a small modification in VDR expression may play a role in such a multipathway process as tumorigenesis.

  11. Nighttime parenting strategies and sleep-related risks to infants.

    Science.gov (United States)

    Volpe, Lane E; Ball, Helen L; McKenna, James J

    2013-02-01

    A large social science and public health literature addresses infant sleep safety, with implications for infant mortality in the context of accidental deaths and Sudden Infant Death Syndrome (SIDS). As part of risk reduction campaigns in the USA, parents are encouraged to place infants supine and to alter infant bedding and elements of the sleep environment, and are discouraged from allowing infants to sleep unsupervised, from bed-sharing either at all or under specific circumstances, or from sofa-sharing. These recommendations are based on findings from large-scale epidemiological studies that generate odds ratios or relative risk statistics for various practices; however, detailed behavioural data on nighttime parenting and infant sleep environments are limited. To address this issue, this paper presents and discusses the implications of four case studies based on overnight observations conducted with first-time mothers and their four-month old infants. These case studies were collected at the Mother-Baby Behavioral Sleep Lab at the University of Notre Dame USA between September 2002 and June 2004. Each case study provides a detailed description based on video analysis of sleep-related risks observed while mother-infant dyads spent the night in a sleep lab. The case studies provide examples of mothers engaged in the strategic management of nighttime parenting for whom sleep-related risks to infants arose as a result of these strategies. Although risk reduction guidelines focus on eliminating potentially risky infant sleep practices as if the probability of death from each were equal, the majority of instances in which these occur are unlikely to result in infant mortality. Therefore, we hypothesise that mothers assess potential costs and benefits within margins of risk which are not acknowledged by risk-reduction campaigns. Exploring why mothers might choose to manage sleep and nighttime parenting in ways that appear to increase potential risks to infants may

  12. An Obesity-Related FTO Variant and the Risk of Preeclampsia in a Finnish Study Population

    Directory of Open Access Journals (Sweden)

    Miira Klemetti

    2011-01-01

    Full Text Available Previous studies have demonstrated a common variant of the obesity and fat mass-related FTO gene, rs9939609, to be associated with obesity, type 2 diabetes, and elevated blood pressure. We investigated whether the FTO SNP rs9939609 is associated with the risk of preeclampsia (PE in a Finnish study population. 485 women with prior PE and 449 women who had given birth after a normotensive pregnancy were genotyped (TaqMan for the SNP rs9939609. The prevalences of genotypes AA, AT, and TT were 15%, 53%, and 32%, respectively, among the PE cases, and 16%, 47%, and 37%, respectively, among the controls (P=0.199. We found no evidence of an association between the FTO SNP rs9939609 and PE. However, our cases were dominated by severe, early-onset PE. Thus, we are unable to exclude an association with the milder, later-onset form of the disease in which the role of maternal metabolic predisposition could be more significant.

  13. Gain of virulence by Soybean mosaic virus on Rsv4-genotype soybeans is associated with a relative fitness loss in a susceptible host.

    Science.gov (United States)

    Wang, Y; Hajimorad, M R

    2016-09-01

    'Gene-for-gene' theory predicts that gain of virulence by an avirulent pathogen on plants expressing resistance (R) genes is associated with fitness loss in susceptible hosts. However, the validity of this prediction has been studied in only a few plant viral pathosystems. In this study, the Soybean mosaic virus (SMV)-Rsv4 pathosystem was exploited to test this prediction. In Rsv4-genotype soybeans, P3 of avirulent SMV strains provokes an as yet uncharacterized resistance mechanism that restricts the invading virus to the inoculated leaves. A single amino acid substitution in P3 functionally converts an avirulent to a virulent strain, suggesting that the genetic composition of P3 plays a crucial role in virulence on Rsv4-genotype soybeans. In this study, we examined the impact of gain of virulence mutation(s) on the fitness of virulent variants derived from three avirulent SMV strains in a soybean genotype lacking the Rsv4 gene. Our data demonstrate that gain of virulence mutation(s) by all avirulent viruses on Rsv4-genotype soybean is associated with a relative fitness loss in a susceptible host. The implications of this finding on the durable deployment of the Rsv4 gene in soybean are discussed.

  14. Interaction between β-hexachlorocyclohexane and ADIPOQ genotypes contributes to the risk of type 2 diabetes mellitus in East Chinese adults

    Science.gov (United States)

    Li, Shushu; Wang, Xichen; Yang, Lu; Yao, Shen; Zhang, Ruyang; Xiao, Xue; Zhang, Zhan; Wang, Li; Xu, Qiujin; Wang, Shou-Lin

    2016-11-01

    Growing evidence links environmental exposure to hexachlorocyclohexanes (HCHs) to the risk of type 2 diabetes mellitus (T2DM), and ADIPOQ that encodes adiponectin is considered as an important gene for T2DM. However, the role of ADIPOQ-HCH interaction on T2DM risk remains unclear. Thus, a paired case-control study was conducted in an East Chinese community. A total of 1446 subjects, including 723 cases and 723 controls matched on age, gender and residence, were enrolled, and 4 types of HCH isomers were measured in serum samples using GC-MS/MS. Additionally, 4 candidate ADIPOQ SNPs (rs182052, rs266729, rs6810075, and rs16861194) were genotyped by TaqMan assay, and plasma adiponectin was measured using ELISA. No associations between 4 SNPs and T2DM risk were found, but T2DM risk significantly increased with serum levels of β-HCH (P < 0.001). Furthermore, the synergistic interaction between β-HCH and rs182052 significantly increased T2DM risk (OR I-additive model = 2.20, OR I-recessive model = 2.13). Additionally, individuals carrying only rs182052 (A allele) with high levels of β-HCH had significant reduction in adiponectin levels (P = 0.016). These results indicate that the interaction between rs182052 and β-HCH might increase the risk of T2DM by jointly decreasing the adiponectin level and potentially trigger T2DM development.

  15. Changes in lifestyle and total homocysteine in relation to MTHFR (C677T) genotype: the Inter99 study

    DEFF Research Database (Denmark)

    Husemoen, LL; Thomsen, TF; Fenger, M;

    2006-01-01

    intervention and re-examination after one year. RESULTS: None of the studied lifestyle changes-- smoking, physical activity, dietary habits, and coffee, tea, and alcohol consumption-- was significantly associated with changes in tHcy, either overall, or in any of the MTHFR genotype subgroups. In addition...

  16. The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers

    DEFF Research Database (Denmark)

    Stage, Claus; Jürgens, Gesche; Guski, Louise Schow

    2017-01-01

    The present study investigated the influence of variations in the carboxylesterase 1 gene (CES1) on the pharmacokinetics of enalapril. Forty-three healthy, Danish, Caucasian volunteers representing different pre-defined genotypes each received 10 mg of enalapril. At specified time points, plasma...

  17. Distribution of HPV Genotypes and Involvement of Risk Factors in Cervical Lesions and Invasive Cervical Cancer: A Study in an Indian Population

    Science.gov (United States)

    Srivastava, Shikha; Shahi, U P; Dibya, Arti; Gupta, Sadhana; Roy, Jagat K

    2014-01-01

    Human papilloma virus (HPV) is considered as the main sexually transmitted etiological agent for the cause and progression of preneoplastic cervical lesions to cervical cancer. This study is discussing the prevalence of HPV and its genotypes in cervical lesions and invasive cervical cancer tissues and their association with various risk factors in women from Varanasi and its adjoining areas in India. A total of 122 cervical biopsy samples were collected from SS Hospital and Indian Railways Cancer Institute and Research Centre, Varanasi and were screened for HPV infection by PCR using primers from L1 consensus region of the viral genome. HPV positive samples were genotyped by type-specific PCR and sequencing. The association of different risk factors with HPV infection in various grades of cervical lesion was evaluated by chi-square test. A total of 10 different HPV genotypes were observed in women with cervicitis, CIN, invasive squamous cell cervical carcinoma and adenocarcinoma. Increased frequency of HPV infection with increasing lesion grade (p=0.002) was observed. HPV16 being the predominant type was found significantly associated with severity of the disease (p=0.03). Various socio- demographic factors other than HPV including high parity (p<0.0001), rural residential area (p<0.0001), elder age (p<0.0001), low socio-economic status (p<0.0001) and women in postmenopausal group (p<0.0001) were also observed to be associated with cervical cancer.These findings show HPV as a direct cause of cervical cancer suggesting urgent need of screening programs and HPV vaccination in women with low socio-economic status and those residing in rural areas. PMID:25035855

  18. Time perspective and perceived risk as related to mammography screening.

    Science.gov (United States)

    Griva, Fay; Anagnostopoulos, Fotios; Potamianos, Gregory

    2013-01-01

    The present study explored the relation of time perspective to perceived risk for breast cancer and mammography screening. Women free from breast cancer (N = 194), eligible for mammography screening in terms of age, completed the Zimbardo Time Perspective Inventory (Zimbardo & Boyd, 1999) and measures of perceived risk, attitude toward performing mammography screening, intention to get a mammogram, and mammography screening behavior. Hierarchical multiple regression analysis revealed that perceived risk of breast cancer (β= .18, p < .01) and intention to be screened (β = .35, p < .01) were significantly associated with mammography screening, after controlling for the effects of sociodemographic (e.g., age, education, and economic level) and health-related variables (e.g., family history of breast cancer and previous benign breast disease). Path analyses including the main psychological variables indicated that perceived risk was indirectly related to intention via attitude (β = .17, p < .01), and to mammography screening through attitude and intention (β = .06, p < .01). Attitude was indirectly related to mammography screening via intention (β = .20, p < .01). Also, a significant indirect association was observed between future orientation and mammography screening, via perceived risk (β = .10, p < .01). Theoretical implications of study findings and suggestions for future research on use of mammography are presented.

  19. Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density

    Directory of Open Access Journals (Sweden)

    Chanock Stephen J

    2010-03-01

    Full Text Available Abstract Background Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here. Methods Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromsø Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI. The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS™ (SAS 9.1.3. Results The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis. Conclusion Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women.

  20. Are all risks equal? Early experiences of poverty-related risk and children's functioning.

    Science.gov (United States)

    Roy, Amanda L; Raver, C Cybele

    2014-06-01

    Using cumulative risk and latent class analysis (LCA) models, we examined how exposure to deep poverty (income-to-needs ratio poverty-related risks (i.e., single-parent household, residential crowding, caregiver depression, and multiple life stressors) in preschool is related to children's future difficulty in school in a longitudinal sample of 602 Head Start-enrolled, low-income families. Results from the LCA revealed 4 risk profiles: low risk, deep poverty and single, single and stressed, and deep poverty and crowded household. Tests of measurement invariance across racial/ethnic groups established that, although patterns of risk are similar across groups (i.e., risks covary in the same way), the prevalence of risk profiles differs. African American families were overrepresented in the "deep poverty and single" profile while Latino and White families were overrepresented in the "deep poverty and crowded" profile. Finally, children's third grade functioning in 3 domains (i.e., academic performance, behavior problems, and self-regulatory skills) was predicted using a cumulative risk index and LCA-identified risk profiles. Both approaches demonstrated that children who experienced higher levels of risk in preschool had worse school performance than children with low levels of risk. However, LCA also revealed that children who experienced "single and stressed" family settings had more behavior problems than low-risk children while children who experienced "deep poverty and crowded" family settings had worse academic performance. The results indicate that all risks are not equal for children's development and highlight the utility of LCA for tailoring intervention efforts to best meet the needs of target populations.

  1. Data on plasma levels of apolipoprotein E, correlations with lipids and lipoproteins stratified by APOE genotype, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Rasmussen, Katrine L.; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2016-01-01

    Data on correlations of plasma apoE with levels of lipids and lipoproteins stratified by APOE genotypes as well as data exploring the association between plasma levels of apoE and risk of ischemic heart disease (IHD) are wanted. The present data on 91,695 individuals from the general population...... provides correlations between plasma levels of apoE and lipids and lipoproteins for the three APOE genotypes ε33, ε44 and ε22, representing each of the three apoE isoforms. Further, data on extreme groups of plasma apoE (highest 5%) versus lower levels of apoE at enrollment explores risk of IHD...... and myocardial infarction (MI) and is given as hazard ratios. In addition, IHD and MI as a function of apoE/high-density lipoprotein (HDL) cholesterol ratio, as well as data on lipids, lipoproteins and apolipoproteins are given as hazard ratios. Data is stratified by gender and presented for the Copenhagen...

  2. Low density lipoprotein receptor related protein 1 and 6 gene variants and ischaemic stroke risk.

    Science.gov (United States)

    Harriott, A M; Heckman, M G; Rayaprolu, S; Soto-Ortolaza, A I; Diehl, N N; Kanekiyo, T; Liu, C-C; Bu, G; Malik, R; Cole, J W; Meschia, J F; Ross, O A

    2015-08-01

    Low density lipoprotein receptor related proteins (LRPs) 1 and 6 have been implicated in cerebral ischaemia. In addition, genetic variation in LRP1 and LRP6 has been linked with various factors that are related to risk of ischaemic stroke. The aim of this study was to examine the association of LRP1 and LRP6 gene variants with risk of ischaemic stroke as part of the Ischemic Stroke Genetics Study (ISGS). A Caucasian series (434 stroke patients, 319 controls) and an African American series (161 stroke patients, 116 controls) were included. Fourteen LRP6 variants and three LRP1 variants were genotyped and assessed for association with ischaemic stroke. In the Caucasian series, significant associations with ischaemic stroke were observed for LRP6 rs2075241 [odds ratio (OR) 0.42, P = 0.023], rs2302685 (OR 0.44, P = 0.049), rs7975614 (OR 0.07, P = 0.017), rs10492120 (OR 0.62, P = 0.036) and rs10743980 (OR 0.66, P = 0.037). Risk of ischaemic stroke was significantly lower for carriers of any of these five protective LRP6 variants (24.0% of subjects) compared to non-carriers (OR 0.57, P = 0.003). The protective association for LRP6 rs2075241 was observed at a similar magnitude across ischaemic stroke subtypes, whilst the effects of rs23022685, rs10492120 and rs10743980 were most apparent for cardioembolic and large vessel stroke. In the African American series, LRP1 rs11172113 was associated with an increased risk of stroke (OR 1.89, P = 0.006). The results of our preliminary study provide evidence that LRP6 and LRP1 variants may be associated with risk of ischaemic stroke. Validation in larger studies is warranted. © 2015 EAN.

  3. Effects of pig genotype (Iberian v. Landrace × Large White) on nutrient digestibility, relative organ weight and small intestine structure at two stages of growth.

    Science.gov (United States)

    Barea, R; Nieto, R; Vitari, F; Domeneghini, C; Aguilera, J F

    2011-02-01

    Although the effects of pig genotype on total-tract apparent digestibility (TTAD) have been widely reported in the literature, there is controversial information on the digestive capacity of indigenous breeds compared with lean-type pigs. The strategy of this study was to test the effects of pig genotype and crude protein (CP) supply on performance, digestive utilization of nutrients, relative organ weight and morphometric analysis of the small intestine. Thirty-eight Iberian (IB) and Landrace × Large White (LD) pigs were used. Three pigs per genotype were slaughtered at approximately 15 kg BW. The remaining pigs were fed one of two diets differing in CP content (13% or 17% as fed) using a pair-fed procedure. Feeding level was restricted at 0.8 × ad libitum of IB pigs. Nutrient digestibility and nitrogen (N) balance trials were performed at 30 and 80 kg BW. Four pigs per dietary treatment and genotype were slaughtered at approximately 50 and 115 kg BW. The gastrointestinal tract and the rest of the visceral organs were weighed and samples of the small intestine were taken to carry out histological and histometrical studies. Daily gain and gain-to-feed ratio were higher in LD than in IB pigs during the fattening and growing-fattening periods (P small intestine was greater in LD than in IB pigs at 50 and 115 kg BW. Histometry showed that IB presented a lower muscle layer thickness than LD pigs in ileum, irrespective of the BW (P small intestine, the main differences between the two genotypes should be attributed to a larger extent to protein and energy utilization in tissues with consequences for the overall efficiency of energy use.

  4. Risk Factors for SARS-Related Deaths in 2003, Beijing

    Institute of Scientific and Technical Information of China (English)

    MIN LIU; WAN-NIAN LIANG; QI CHEN; XUE-QIN XIE; JIANG WU; XIONG HE; ZE-JUN LIU

    2006-01-01

    Objective To study the potential risk factors for severe acute respiratory syndromes (SARS)-related deaths in Beijing. Methods Epidemiological data were collected among the confirmed SARS patients officially reported by Beijing Centers for Disease Control and Prevention (BCDC), and information was also supplemented by a follow-up case survey. Chi-square test and multivariate stepwise logistic regression analysis were performed. Results Old age (over 60 years) was found to be significantly associated with SARS-related deaths in the univariate analysis. Also, history of contacting SARS patients within 2 weeks prior to the onset of illness, health occupation, and inferior hospital ranking as well as longer interval of clinic consulting (longer than 1 day) were the risk factors for SARS-related deaths. Multivariate stepwise logistic regression analysis found four risk factors for SARS-related deaths. Conclusion Old age (over 60 years) is the major risk factor for SARS-related deaths.Moreover, hospital health workers, the designated hospitals for SARS clinical services and the interval of consulting doctors (less than 1 day) are protective factors for surviving from SARS.

  5. Presence of histopathological premalignant lesions and infection caused by high-risk genotypes of human papillomavirus in patients with suspicious cytological and colposcopy results: A prospective study

    Directory of Open Access Journals (Sweden)

    Golubović Mileta

    2017-01-01

    Full Text Available Background/Aim. In patients with premalignant cervical lesions, human papillomavirus (HPV infection, at any moment, may be spontaneously eliminated, or may persist or transform cervical epithelium from a lower to a higher degree. Due to that, it is necessary to wisely select the patients who are at high risk of cancer development. The aim of the study was to establish the interdependence between a suspicious Papanicolaou (Pap test and colposcopy with the infection caused by high-risk genotypes of human papillomavirus and the presence of premalignant cervical lesions. Methods. This prospective study used cytological, colposcopy, real-time polymerase chain reaction (PCR of high-risk genotypes of human papillomavirus and histopathological analysis of cervical biopsy specimen. Out of 2,578 female patients sent to cytological analyses in Clinical Center of Montenegro, during 2012, 2013 and 2014, the study included 80 women who had to submit their biopsy specimens due to a suspicious Pap test and atypical colposcopy results. Results. In the group of 80 (3.1%; n = 80/2,578 of the selected female patients with suspicious Pap test and colposcopy, 2/3 or 56 (70% of them had cervicitis, and 1/3 or 24 (30% had cervical intraepithelial neoplasia. The most common type in cervical intraepithelial neoplasia was HPV16 in 8 female patients, ie 61.53% out of the number of infected, or 33.33% out of the total number of premalignant lesions. Conclusion. Patients with suspicious Papanicolaou test, colposcopy results and infection which is caused by high-risk HPV infection (HPV 16 in particular often have premalignant cervical lesions. In these cases, histopathological confirmation of lesions is mandatory, since it serves as a definitive diagnostic procedure.

  6. Coffee and tea consumption, genotype-based CYP1A2 and NAT2 activity and colorectal cancer risk-results from the EPIC cohort study.

    Science.gov (United States)

    Dik, Vincent K; Bueno-de-Mesquita, H B As; Van Oijen, Martijn G H; Siersema, Peter D; Uiterwaal, Cuno S P M; Van Gils, Carla H; Van Duijnhoven, Fränzel J B; Cauchi, Stéphane; Yengo, Loic; Froguel, Philippe; Overvad, Kim; Bech, Bodil H; Tjønneland, Anne; Olsen, Anja; Boutron-Ruault, Marie-Christine; Racine, Antoine; Fagherazzi, Guy; Kühn, Tilman; Campa, Daniele; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Peppa, Eleni; Oikonomou, Eleni; Palli, Domenico; Grioni, Sara; Vineis, Paolo; Tumino, Rosaria; Panico, Salvatore; Peeters, Petra H M; Weiderpass, Elisabete; Engeset, Dagrun; Braaten, Tonje; Dorronsoro, Miren; Chirlaque, María-Dolores; Sánchez, María-José; Barricarte, Aurelio; Zamora-Ros, Raul; Argüelles, Marcial; Jirström, Karin; Wallström, Peter; Nilsson, Lena M; Ljuslinder, Ingrid; Travis, Ruth C; Khaw, Kay-Tee; Wareham, Nick; Freisling, Heinz; Licaj, Idlir; Jenab, Mazda; Gunter, Marc J; Murphy, Neil; Romaguera-Bosch, Dora; Riboli, Elio

    2014-07-15

    Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7 ± 8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC. © 2013 UICC.

  7. Elite Athletes experiences with risk related to Cardiac Screening

    DEFF Research Database (Denmark)

    Christensen, Jonas Schmidt; Thing, Lone Friis

    Elite Athletes experiences with risks related to Cardiac Screening Jonas Schmidt Christensen1, Lone Friis Thing1 1University of Copenhagen - Department of Nutrition, Exercise and Sports (NEXS), Cardiac screening of elite athletes are recommended by both the American Heart Association & the European...... is dominated by studies with a clinical medical focus and studies of athlete’s perspectives on cardiac screening are consequently an absence. By using an interpretive sociological perspective (Denzin 2001) and qualitative research done with elite athletes of both gender this paper seeks to explore how elite...... athletes experience risks associated with cardiac screening. To make possible an analysis of how elite athletes come to an understanding of and position themselves in relation to the risk discourse (Lupton 2013) they are met by, the focus is on Foucault’s technologies of the self and a subjectivity...

  8. Association between HLA-G genotype and risk of pre-eclampsia: a case-control study using family triads

    DEFF Research Database (Denmark)

    Hylenius, Sine; Andersen, Anne-Marie Nybo; Melbye, Mads;

    2004-01-01

    that it is caused by immune- maladaptation. The MHC class Ib gene, HLA-G, is expressed in the placenta and seems to have immunomodulatory functions. Aberrant HLA-G mRNA and protein expression in pre-eclamptic placentas have been reported. Here, we have investigated detailed HLA-G genotypes in a case-control study...... of 155 family triads of mother, father and newborn. Among primiparas, an overrepresentation of a homozygous HLA-G genotype was detected in the 40 pre-eclamptic offspring compared to the 70 controls [P = 0.002, Fisher's exact test; odds ratio 5.57 (95% CI 1.79-17.31)]. Further analyses suggested...... that the differences between pre-eclamptic cases and controls primarily were accomplished by a different transmission from the father of a 14 bp deletion/insertion polymorphism in exon 8 (P = 0.006, Fisher's exact test), which previously has been linked to differences in the levels of HLA-G expression and in HLA-G m...

  9. Financial Constraints and the Risk-Return Relation

    OpenAIRE

    Tao Wang

    2007-01-01

    Stock return volatilities are related to firms' financial status. Financially constrained firms are more volatile. Their stock return volatilities react more negatively to lagged return changes than financially unconstrained firms. This strong negative relation between volatilities and lagged returns for financially constrained firms are not affected by industry differences or firm leverage. Moreover, the debt-equity ratio is not as important as financial constraints for the firm-level risk-r...

  10. CKD increases the risk of age-related macular degeneration.

    Science.gov (United States)

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-04-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerular filtration rate macular degeneration was 3.9% in participants with no/mild chronic kidney disease (35 of 897) and 17.5% in those with moderate chronic kidney disease (50 of 286). After adjusting for age, sex, cigarette smoking, hypertension, complement factor H polymorphism, and other risk factors, persons with moderate chronic kidney disease were 3 times more likely to develop early age-related macular degeneration than persons with no/mild chronic kidney disease (odds ratio = 3.2; 95% confidence interval, 1.8 to 5.7, P macular degeneration (odds ratio = 2.0; 95% confidence interval, 1.5 to 2.8, P chronic kidney disease have a higher risk of early age-related macular degeneration, suggesting the possibility of shared pathophysiologic mechanisms between the two conditions.

  11. Diversity in the carotenoid profiles and the expression of genes related to carotenoid accumulation among citrus genotypes

    OpenAIRE

    Ikoma, Yoshinori; Matsumoto, Hikaru; Kato, Masaya

    2016-01-01

    Carotenoids are not only important to the plants themselves but also are beneficial to human health. Since citrus fruit is a good source of carotenoids for the human diet, it is important to study carotenoid profiles and the accumulation mechanism in citrus fruit. Thus, in the present paper, we describe the diversity in the carotenoid profiles of fruit among citrus genotypes. In regard to carotenoids, such as β-cryptoxanthin, violaxanthin, lycopene, and β-citraurin, the relationship between t...

  12. Multi-allele genotyping platform for the simultaneous detection of mutations in the Wilson disease related ATP7B gene.

    Science.gov (United States)

    Amvrosiadou, Maria; Petropoulou, Margarita; Poulou, Myrto; Tzetis, Maria; Kanavakis, Emmanuel; Christopoulos, Theodore K; Ioannou, Penelope C

    2015-12-01

    Wilson's disease is an inherited disorder of copper transport in the hepatocytes with a wide range of genotype and phenotype characteristics. Mutations in the ATP7B gene are responsible for the disease. Approximately, over 500 mutations in the ATP7B gene have been described to date. We report a method for the simultaneous detection of the ten most common ATP7B gene mutations in Greek patients. The method comprises 3 simple steps: (i) multiplex PCR amplification of fragments in the ATP7B gene flanking the mutations (ii) multiplex primer extension reaction of the unpurified amplification products using allele-specific primers and (iii) visual detection of the primer extension reaction products within minutes by means of dry-reagent multi-allele dipstick assay using anti-biotin conjugated gold nanoparticles. Optimization studies on the efficiency and specificity of the PEXT reaction were performed. The method was evaluated by genotyping 46 DNA samples of known genotype and 34 blind samples. The results were fully concordant with those obtained by reference methods. The method is simple, rapid, cost-effective and it does not require specialized instrumentation or highly qualified personnel.

  13. Signaling Pathways Related to Protein Synthesis and Amino Acid Concentration in Pig Skeletal Muscles Depend on the Dietary Protein Level, Genotype and Developmental Stages.

    Science.gov (United States)

    Liu, Yingying; Li, Fengna; Kong, Xiangfeng; Tan, Bie; Li, Yinghui; Duan, Yehui; Blachier, François; Hu, Chien-An A; Yin, Yulong

    2015-01-01

    Muscle growth is regulated by the homeostatic balance of the biosynthesis and degradation of muscle proteins. To elucidate the molecular interactions among diet, pig genotype, and physiological stage, we examined the effect of dietary protein concentration, pig genotype, and physiological stages on amino acid (AA) pools, protein deposition, and related signaling pathways in different types of skeletal muscles. The study used 48 Landrace pigs and 48 pure-bred Bama mini-pigs assigned to each of 2 dietary treatments: lower/GB (Chinese conventional diet)- or higher/NRC (National Research Council)-protein diet. Diets were fed from 5 weeks of age to respective market weights of each genotype. Samples of biceps femoris muscle (BFM, type I) and longissimus dorsi muscle (LDM, type II) were collected at nursery, growing, and finishing phases according to the physiological stage of each genotype, to determine the AA concentrations, mRNA levels for growth-related genes in muscles, and protein abundances of mechanistic target of rapamycin (mTOR) signaling pathway. Our data showed that the concentrations of most AAs in LDM and BFM of pigs increased (Ppigs had generally higher (Ppigs. The mRNA levels for myogenic determining factor, myogenin, myocyte-specific enhancer binding factor 2 A, and myostatin of Bama mini-pigs were higher (Ppigs, while total and phosphorylated protein levels for protein kinase B, mTOR, and p70 ribosomal protein S6 kinases (p70S6K), and ratios of p-mTOR/mTOR, p-AKT/AKT, and p-p70S6K/p70S6K were lower (Ppig genotype-dependent effect of dietary protein on the levels for mTOR and p70S6K. When compared with the higher protein-NRC diet, the lower protein-GB diet increased (Ppigs, but repressed (Ppigs. The higher protein-NRC diet increased ratio of p-mTOR/mTOR in Landrace pigs. These findings indicated that the dynamic consequences of AA profile and protein deposition in muscle tissues are the concerted effort of distinctive genotype, nutrient status, age, and

  14. Explanatory risk factors in the relations between schizotypy and indicators of suicide risk.

    Science.gov (United States)

    Jahn, Danielle R; DeVylder, Jordan E; Hilimire, Matthew R

    2016-04-30

    Schizotypy has been linked to suicide risk, but it is not known whether established suicide-related risk factors mediate this relation. The aim of this study was to assess the mediating effects of depressive symptoms, social anxiety, self-esteem, and intimate disclosure in peer relationships in the relation between interpersonal schizotypy and suicide ideation or lifetime suicide attempts. This aim was tested in 590 young adults using a nonparametric bootstrapping procedure. After inclusion of the mediators, interpersonal schizotypy was no longer directly associated with either suicide ideation or lifetime suicide attempts. Depression and self-esteem mediated the relation between interpersonal schizotypy and suicide ideation. No variables mediated the relation between interpersonal schizotypy and lifetime suicide attempts, and there were no significant direct relations when mediators were included. Schizotypy appears to be a distal risk factor for suicidal behavior; assessing depressive symptoms and self-esteem may provide more proximal information about suicide risk, and may be targets for mitigating suicide risk in individuals with schizotypy.

  15. Practical approaches to the assessment of work-related risks.

    Science.gov (United States)

    Kogi, K

    1993-01-01

    The control of work-related risks calls for practical improvements in job content and the working environment. For assessment of risks, it is essential to resort to the most practical methods in the local context. Important common methods are examination of the process, equipment and organisation of work, walk-through surveys, evaluation of risk factors in the working environment, inquiries and questionnaires as well as monitoring of various health indicators. Biological tests and other health indicators can thus only be regarded as components of overall occupational health-risk assessment strategy, with their advantages, disadvantages and limitations. Important are the validity of biological tests and the ethical aspects related to their use, such as confidentiality of data and the individual worker's informed consent, preference being given to noninvasive-methods. Occupational health services should thus play a positive role by providing practical advice, training and information for participatory risk assessment keeping in view such an overall strategy that facilitates immediate preventive action. Biological monitoring should be applied when the additional guidance it provides on preventive action is essential. Proposals to use biological monitoring must emphasise this justification aspect.

  16. Spontaneous ipsilateral subconjunctival hemorrhage and the related risk factors

    Directory of Open Access Journals (Sweden)

    Nikolas Ziakas

    2011-06-01

    Full Text Available The aim of the report is to assess the risk factors among patients with spontaneous ipsilateral subconjunctival hemorrhage (SCH who presented to the outpatients’ department in General Hospital of Veria, Veria, Greece. Thirty-five patients with SCH participated in the study. A thorough case history was taken and a full ophthalmic examination was performed to identify the risk factors related to the clinical finding. The common hematological parameters associated with the coagulation profile of each patient were evaluated. With the exception of SCH, the ophthalmic examination was normal in all patients. Identified risk factors include history of systemic hypertension (21 patients [60%], mean systolic value: 170 mmHg±15 mmHg, strenuous exercise [19 patients (54%] and minor ocular trauma [5 patients (14%]. Other risk factors [each in 2 patients (6%] included: diabetes mellitus, smoking, severe cough, straining at stool, and weight lifting. Seven patients (20% were under medication related to bleeding diathesis. The values of the blood coagulation parameters were within the normal limits in all patients. Twenty-nine patients (83% had elevated blood pressure during the ophthalmological examination. Our study provides documentation regarding the potential risk factors associated with SCH. It is interesting to observe the high incidence of hypertension among the patients with SCH. Therefore, it is highly recommended that the blood pressure be checked in all patients with SCH and that the patients be referred to a general practitioner for further management if indicated.

  17. Pregnancy-related characteristics and breast cancer risk.

    Science.gov (United States)

    Brasky, Theodore M; Li, Yanli; Jaworowicz, David J; Potischman, Nancy; Ambrosone, Christine B; Hutson, Alan D; Nie, Jing; Shields, Peter G; Trevisan, Maurizio; Rudra, Carole B; Edge, Stephen B; Freudenheim, Jo L

    2013-09-01

    Breast tissues undergo extensive physiologic changes during pregnancy, which may affect breast carcinogenesis. Gestational hypertension, preeclampsia/eclampsia, gestational diabetes, pregnancy weight gain, and nausea and vomiting (N&V) during pregnancy may be indicative of altered hormonal and metabolic profiles and could impact breast cancer risk. Here, we examined associations between these characteristics of a woman's pregnancy and her subsequent breast cancer risk. Participants were parous women that were recruited to a population-based case-control study (Western New York Exposures and Breast Cancer Study). Cases (n = 960), aged 35-79 years, had incident, primary, histologically confirmed breast cancer. Controls (n = 1,852) were randomly selected from motor vehicle records (pregnancy experiences. Multivariable-adjusted logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). N&V during pregnancy was inversely associated with breast cancer risk. Relative to those who never experienced N&V, ever experiencing N&V was associated with decreased risk (OR 0.69, 95% CI 0.56-0.84) as were increased N&V severity (p trend pregnancies (p trend pregnancies. Associations were stronger for more recent pregnancies (breast cancer subtype including estrogen receptor and HER2 expression status. Other pregnancy characteristics examined were not associated with risk. We observed strong inverse associations between pregnancy N&V and breast cancer risk. Replication of these findings and exploration of underlying mechanisms could provide important insight into breast cancer etiology and prevention.

  18. Risk Factors Associated with Peritoneal-Dialysis-Related Peritonitis

    Directory of Open Access Journals (Sweden)

    Julia Kerschbaum

    2012-01-01

    Full Text Available Background. Peritonitis represents a major complication of peritoneal dialysis (PD. The aim of this paper was to systematically collect data on patient-related risk factors for PD-associated peritonitis, to analyze the methodological quality of these studies, and to summarize published evidence on the particular risk factors. Methods. Studies were identified by searches of Pubmed (1990–2012 and assessed for methodological quality by using a modified form of the STROBE criteria. Results. Thirty-five methodologically acceptable studies were identified. The following nonmodifiable risk factors were considered valid and were associated with an increased risk of peritonitis: ethnicity, female gender, chronic lung disease, coronary artery disease, congestive heart failure, cardiovascular disease, hypertension, antihepatitis C virus antibody positivity, diabetes mellitus, lupus nephritis or glomerulonephritis as underlying renal disease, and no residual renal function. We also identified the following modifiable, valid risk factors for peritonitis: malnutrition, overweight, smoking, immunosuppression, no use of oral active vitamin D, psychosocial factors, low socioeconomic status, PD against patient’s choice, and haemodialysis as former modality. Discussion. Modifiable and nonmodifiable risk factors analyzed in this paper might serve as a basis to improve patient care in peritoneal dialysis.

  19. Comparison of the performance in detection of HPV infections between the high-risk HPV genotyping real time PCR and the PCR-reverse dot blot assays.

    Science.gov (United States)

    Zhang, Lahong; Dai, Yibei; Chen, Jiahuan; Hong, Liquan; Liu, Yuhua; Ke, Qiang; Chen, Yiwen; Cai, Chengsong; Liu, Xia; Chen, Zhaojun

    2017-08-29

    A new multiplex real-time PCR assay, the high-risk HPV genotyping real time PCR assay (HR HPV RT-PCR), has been developed to detect 15 high-risk HPV types with respective viral loads. In this report, a total of 684 cervical specimens from women diagnosed with vaginitis were assessed by the HR HPV RT-PCR and the PCR reaction and reverse dot blot (PCR-RDB) assays, using a PCR-sequencing method as a reference standard. A total coincidence of 97.7% between the HR HPV RT PCR and the PCR-RDB assays was determined with a Kappa value of 0.953. The HR HPV RT PCR assay had sensitivity, specificity, and concordance rates (accuracy) of 99.7%, 99.7%, and 99.7%, respectively, as confirmed by PCR-sequencing, while the PCR-RDB assay had respective rates of 98.8%, 97.1%, and 98.0%. The overall rate of HPV infection, determined by PCR-sequencing, in women diagnosed with vaginitis was 49.85%, including 36.26% of single infection and 13.6% of multiple infections. The most common infections among the 15 high-risk HPV types in women diagnosed with vaginitis were HPV-52, HPV-16, and HPV-58, with a total detection rate of 10.23%, 7.75%, and 5.85%, respectively. We conclude that the HR HPV RT PCR assay exhibits better clinical performance than the PCR-RDB assay, and is an ideal alternative method for HPV genotyping. In addition, the HR HPV RT PCR assay provides HPV DNA viral loads, and could serve as a quantitative marker in the diagnosis and treatment of single and multiple HPV infections. © 2017 Wiley Periodicals, Inc.

  20. Relative risks of low birthweight in Scotland 1980-2.

    OpenAIRE

    Pickering, R.M.

    1987-01-01

    Routinely collected data for 187,000 Scottish singleton livebirths in 1980-2 were used to relate the risk of birthweight below 2500 g, 2000 g, 1500 g, and 1000 g to sex of infant and nine maternal factors. Maternal height was a major predictor of birthweight below 2500g but was less important in predicting birthweight in the lower intervals. A history of prenatal death and spontaneous abortion was important for all four intervals and was associated with most extreme risks for birthweight belo...

  1. Risk Estimates and Risk Factors Related to Psychiatric Inpatient Suicide—An Overview

    Science.gov (United States)

    Madsen, Trine; Erlangsen, Annette; Nordentoft, Merete

    2017-01-01

    People with mental illness have an increased risk of suicide. The aim of this paper is to provide an overview of suicide risk estimates among psychiatric inpatients based on the body of evidence found in scientific peer-reviewed literature; primarily focusing on the relative risks, rates, time trends, and socio-demographic and clinical risk factors of suicide in psychiatric inpatients. Psychiatric inpatients have a very high risk of suicide relative to the background population, but it remains challenging for clinicians to identify those patients that are most likely to die from suicide during admission. Most studies are based on low power, thus compromising quality and generalisability. The few studies with sufficient statistical power mainly identified non-modifiable risk predictors such as male gender, diagnosis, or recent deliberate self-harm. Also, the predictive value of these predictors is low. It would be of great benefit if future studies would be based on large samples while focusing on modifiable predictors over the course of an admission, such as hopelessness, depressive symptoms, and family/social situations. This would improve our chances of developing better risk assessment tools. PMID:28257103

  2. Risk Estimates and Risk Factors Related to Psychiatric Inpatient Suicide-An Overview.

    Science.gov (United States)

    Madsen, Trine; Erlangsen, Annette; Nordentoft, Merete

    2017-03-02

    People with mental illness have an increased risk of suicide. The aim of this paper is to provide an overview of suicide risk estimates among psychiatric inpatients based on the body of evidence found in scientific peer-reviewed literature; primarily focusing on the relative risks, rates, time trends, and socio-demographic and clinical risk factors of suicide in psychiatric inpatients. Psychiatric inpatients have a very high risk of suicide relative to the background population, but it remains challenging for clinicians to identify those patients that are most likely to die from suicide during admission. Most studies are based on low power, thus compromising quality and generalisability. The few studies with sufficient statistical power mainly identified non-modifiable risk predictors such as male gender, diagnosis, or recent deliberate self-harm. Also, the predictive value of these predictors is low. It would be of great benefit if future studies would be based on large samples while focusing on modifiable predictors over the course of an admission, such as hopelessness, depressive symptoms, and family/social situations. This would improve our chances of developing better risk assessment tools.

  3. Risk Estimates and Risk Factors Related to Psychiatric Inpatient Suicide—An Overview

    Directory of Open Access Journals (Sweden)

    Trine Madsen

    2017-03-01

    Full Text Available People with mental illness have an increased risk of suicide. The aim of this paper is to provide an overview of suicide risk estimates among psychiatric inpatients based on the body of evidence found in scientific peer-reviewed literature; primarily focusing on the relative risks, rates, time trends, and socio-demographic and clinical risk factors of suicide in psychiatric inpatients. Psychiatric inpatients have a very high risk of suicide relative to the background population, but it remains challenging for clinicians to identify those patients that are most likely to die from suicide during admission. Most studies are based on low power, thus compromising quality and generalisability. The few studies with sufficient statistical power mainly identified non-modifiable risk predictors such as male gender, diagnosis, or recent deliberate self-harm. Also, the predictive value of these predictors is low. It would be of great benefit if future studies would be based on large samples while focusing on modifiable predictors over the course of an admission, such as hopelessness, depressive symptoms, and family/social situations. This would improve our chances of developing better risk assessment tools.

  4. Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

    DEFF Research Database (Denmark)

    Hoeft, B.; Linseisen, J.; Beckmann, L.

    2010-01-01

    a generalized linear model framework. On the genotype level, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), phospholipase A2 group VI (PLA2G6) and transient receptor potential vanilloid 3 were associated with higher risk for CRC, whereas prostaglandin E receptor 2 (PTGER2) was associated with lower CRC...

  5. The relation of risk assessment and health impact assessment

    DEFF Research Database (Denmark)

    Ádám, Balázs; Gulis, Gabriel

    2013-01-01

    as a powerful tool for the evaluation of potential health consequences of planned measures. It is often discussed whether HIA is not just another term or form of risk assessment and what is their relation. Our aim is to discuss similarities and differences between the two methods so as to clarify......The level and distribution of health risks in a society is substantially influenced by measures of various policies, programmes or projects. Risk assessment can evaluate the nature, likelihood and severity of an adverse effect. Health impact assessment (HIA) provides similar function when used...... standardised scientific methods to characterise the probability and magnitude of harm caused by a hazard, preferably in a quantitative manner. In turn, HIA is a process to assess future impacts of recent proposals and is dominated by qualitative evaluation. It makes a projection for a future scenario rather...

  6. Expression of Hepatitis B virus surface antigen (HBsAg from genotypes A, D and F and influence of amino acid variations related or not to genotypes on HBsAg detection

    Directory of Open Access Journals (Sweden)

    Natalia M. Araujo

    Full Text Available The impact of hepatitis B virus (HBV genotypes on the sensitivity of surface antigen (HBsAg detection assays has been poorly investigated. Here, plasmids carrying consensus or variant coding sequences for HBV surface proteins from genotypes A, D and F, were constructed. HBsAg levels were evaluated in medium and extracts of transfected CHO cells by a commercial polyclonal-based assay. We show that HBsAg detection values of consensus forms from genotypes D and F were, respectively, 37% and 30% lower than those obtained by genotype A. However, the presence of two single variations, T143M in genotype A, and T125M in genotype D, produced a decrease of 44% and an increase of 34%, respectively, on HBsAg mean values in comparison with their consensus forms. In conclusion, HBsAg detection levels varied among HBV genotypes. However, unique amino acid substitutions not linked to genotypes, such as T125M and T143M described here, should have more implications in HBV immunological diagnostics than the set of variations characteristic of each HBV genotype.

  7. Expression of Hepatitis B virus surface antigen (HBsAg from genotypes A, D and F and influence of amino acid variations related or not to genotypes on HBsAg detection

    Directory of Open Access Journals (Sweden)

    Natalia M. Araujo

    2009-08-01

    Full Text Available The impact of hepatitis B virus (HBV genotypes on the sensitivity of surface antigen (HBsAg detection assays has been poorly investigated. Here, plasmids carrying consensus or variant coding sequences for HBV surface proteins from genotypes A, D and F, were constructed. HBsAg levels were evaluated in medium and extracts of transfected CHO cells by a commercial polyclonal-based assay. We show that HBsAg detection values of consensus forms from genotypes D and F were, respectively, 37% and 30% lower than those obtained by genotype A. However, the presence of two single variations, T143M in genotype A, and T125M in genotype D, produced a decrease of 44% and an increase of 34%, respectively, on HBsAg mean values in comparison with their consensus forms. In conclusion, HBsAg detection levels varied among HBV genotypes. However, unique amino acid substitutions not linked to genotypes, such as T125M and T143M described here, should have more implications in HBV immunological diagnostics than the set of variations characteristic of each HBV genotype.

  8. PSA and androgen-related gene (AR, CYP17, and CYP19) polymorphisms and the risk of adenocarcinoma at prostate biopsy

    DEFF Research Database (Denmark)

    dos Santos, Rodrigo Mattos; de Jesus, Carlos Márcio Nóbrega; Trindade Filho, José Carlos Souza;

    2008-01-01

    The aim of the present study was to examine the impact of polymorphisms in prostate-specific antigen (PSA) and androgen-related genes (AR, CYP17, and CYP19) on prostate cancer (PCa) risk in selected high-risk patients who underwent prostate biopsy. Blood samples and prostate tissues were obtained...... for DNA analysis. Single-nucleotide polymorphisms in the 50-untranslated regions (UTRs) of the PSA (substitution A>G at position-158) and CYP17 (substitution T>C at 50-UTR) genes were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism assays. The CAG and TTTA repeats...... in the AR and CYP19 genes, respectively, were genotyped by PCR-based GeneScan analysis. Patients with the GG genotype of the PSA gene had a higher risk of PCa than those with the AG or AA genotype (OR=3.79, p=0.00138). The AA genotype was associated with lower PSA levels (6.44 +/- 1.64 ng=mL) compared...

  9. Desmanthus GENOTYPES

    Directory of Open Access Journals (Sweden)

    JOSÉ HENRIQUE DE ALBUQUERQUE RANGEL

    2015-01-01

    Full Text Available Desmanthus is a genus of forage legumes with potential to improve pastures and livestock produc-tion on clay soils of dry tropical and subtropical regions such as the existing in Brazil and Australia. Despite this patterns of natural or enforced after-ripening of Desmanthus seeds have not been well established. Four year old seed banks of nine Desmanthus genotypes at James Cook University were accessed for their patterns of seed softe-ning in response to a range of temperatures. Persistent seed banks were found to exist under all of the studied ge-notypes. The largest seeds banks were found in the genotypes CPI 78373 and CPI 78382 and the smallest in the genotypes CPI’s 37143, 67643, and 83563. An increase in the percentage of softened seeds was correlated with higher temperatures, in two patterns of response: in some accessions seeds were not significantly affected by tempe-ratures below 80º C; and in others, seeds become soft when temperature rose to as little as 60 ºC. At 80 °C the heat started to depress germination. High seed production of Desmanthus associated with dependence of seeds on eleva-ted temperatures to softening can be a very important strategy for plants to survive in dry tropical regions.

  10. Relative Risk Appraisal, the September 11 Attacks, and Terrorism-Related Fears

    Science.gov (United States)

    Marshall, Randall D.; Bryant, Richard A.; Amsel, Lawrence; Suh, Eun Jung; Cook, Joan M.; Neria, Yuval

    2013-01-01

    There are now replicated findings that posttraumatic stress disorder (PTSD) symptoms related to the September 11, 2001, attacks occurred in large numbers of persons who did not fit the traditional definition of exposure to a traumatic event. These data are not explained by traditional epidemiologic “bull’s eye” disaster models, which assume the psychological effects are narrowly, geographically circumscribed, or by existing models of PTSD onset. In this article, the authors develop a researchable model to explain these and other terrorism-related phenomena by synthesizing research and concepts from the cognitive science, risk appraisal, traumatic stress, and anxiety disorders literatures. They propose the new term relative risk appraisal to capture the psychological function that is the missing link between the event and subjective response in these and other terrorism-related studies to date. Relative risk appraisal highlights the core notion from cognitive science that human perception is an active, multidimensional process, such that for unpredictable societal threats, proximity to the event is only one of several factors that influence behavioral responses. Addressing distortions in relative risk appraisal effectively could reduce individual and societal vulnerability to a wide range of adverse economic and ethnopolitical consequences to terrorist attacks. The authors present ways in which these concepts and related techniques can be helpful in treating persons with September 11– or terrorism-related distress or psychopathology. PMID:17516775

  11. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  12. Building-related risk factors and work-related lower respiratory symptoms in 80 office buildings

    Energy Technology Data Exchange (ETDEWEB)

    Mendell, M.J.; Naco, G.M.; Wilcox, T.G.; Sieber, W.K.

    2002-01-01

    We assessed building-related risk factors for lower respiratory symptoms in office workers. The National Institute for Occupational Safety and Health in 1993 collected data during indoor environmental health investigations of workplaces. We used multivariate logistic regression analyses to assess relationships between lower respiratory symptoms in office workers and risk factors plausibly related to microbiologic contamination. Among 2,435 occupants in 80 office buildings, frequent, work-related multiple lower respiratory symptoms were strongly associated, in multivariate models, with two risk factors for microbiologic contamination: poor pan drainage under cooling coils and debris in outside air intake. Associations tended to be stronger among those with a history of physician-diagnosed asthma. These findings suggest that adverse lower respiratory health effects from indoor work environments, although unusual, may occur in relation to poorly designed or maintained ventilation systems, particularly among previously diagnosed asthmatics. These findings require confirmation in more representative buildings.

  13. Analysis of related risk factors for pancreatic fistula after pancreaticoduodenectomy

    Institute of Scientific and Technical Information of China (English)

    Qi-Song Yu; He-Chao Huang; Feng Ding; Xin-Bo Wang

    2016-01-01

    Objective:To explore the related risk factors for pancreatic fistula after pancreaticoduodenectomy to provide a theoretical evidence for effectively preventing the occurrence of pancreatic fistula.Methods:A total of 100 patients who were admitted in our hospital from January, 2012 to January, 2015 and had performed pancreaticoduodenectomy were included in the study. The related risk factors for developing pancreatic fistula were collected for single factor and Logistic multi-factor analysis.Results:Among the included patients, 16 had pancreatic fistula, and the total occurrence rate was 16% (16/100). The single-factor analysis showed that the upper abdominal operation history, preoperative bilirubin, pancreatic texture, pancreatic duct diameter, intraoperative amount of bleeding, postoperative hemoglobin, and application of somatostatin after operation were the risk factors for developing pancreatic fistula (P<0.05). The multi-factor analysis showed that the upper abdominal operation history, the soft pancreatic texture, small pancreatic duct diameter, and low postoperative hemoglobin were the dependent risk factors for developing pancreatic fistula (OR=4.162, 6.104, 5.613, 4.034,P<0.05).Conclusions:The occurrence of pancreatic fistula after pancreaticoduodenectomy is closely associated with the upper abdominal operation history, the soft pancreatic texture, small pancreatic duct diameter, and low postoperative hemoglobin; therefore, effective measures should be taken to reduce the occurrence of pancreatic fistula according to the patients’own conditions.

  14. Workplace strategies for the control of work-related risks.

    Science.gov (United States)

    Kogi, K

    1993-10-01

    The prevention of work-related diseases and disorders, including those of neuropsychobehavioral nature, calls for integrated action to improve both job content and the working environment. Recent international labor standards have highlighted the importance of a good safety and health management system that ensures the assessment of risks and the appropriate control of these risks. Internationally, programs to cope with work-related risks place an increasing emphasis on participatory management of preventive measures, practical methods of risk assessment, and immediate improvements with the support of action-oriented training and information. Psychosocial factors, work performance, and job content need special attention. Workplace strategies must be developed by active participation of employers and workers, with their informed consent. These strategies and linked training activities should build on local practice and achievements rather than administrative models and be geared to the real local needs. In coping with the neurobehavioral effects, international sharing of positive experiences is useful especially with respect to: (i) providing information on potential neurobehavioral effects including labeling, safety datasheets, and precautions; (ii) providing practical advice about locally achieved improvements; (iii) providing action-oriented training; and (iv) creating opportunities for participatory workplace improvements.

  15. Single-tube-genotyping of gastric cancer related SNPs by directly using whole blood and paper-dried blood as starting materials

    Institute of Scientific and Technical Information of China (English)

    Huan Huang; Ying Bu; Guo-Hua Zhou

    2006-01-01

    AIM: To demonstrate an inexpensive method for typing gastric cancer related single nucleotide polymorphisms (SNPs) using whole blood or paper-dried blood as starting materials.METHODS: PCR amplification is directly carried out from the whole blood or paper-dried blood sample without any DNA extraction step. Before PCR, a blood sample, four primers, and all of biological reagents necessary for PCR were added at a time; After PCR, the amplified products were directly separated by slab gel electrophoresis or microchip CE without any purification. SNP typing was performed by tetra-primer PCR with two inner primers specific to each allele and two outer primers defining the length of allele-specific amplicons. Genotypes were directly discriminated by the size of amplicons specific to each allele, thereby avoiding any post-PCR process.RESULTS: Using a special PCR buffer, inhibitory substances in blood (including the anticoagulant in blood) and filter paper were effectively suppressed;a "true" single-tube-genotyping is thus realized. We successfully determined genotypes IL-1B-511 and IL-1B-31 polymorphisms at the gene IL-1B by using whole-blood and paper-dried blood samples as starting materials respectively. The method is so sensitive that 0.5-1.0 μL of blood sample is enough to give a satisfactory typing results. The genotyping results were confirmed by RFLP-PCR using purified genome DNA,indicating that amplification specificity was not affected by inhibitory components (including coagulants) in blood or filter paper.CONCLUSION: Compared with SNP typing methods based on purified DNA, the proposed method is laborsaving, simple, inexpensive, and less cross-contaminated.It is promising to use this method to type other SNPs.

  16. Relative deprivation and risk factors for obesity in Canadian adolescents.

    Science.gov (United States)

    Elgar, Frank J; Xie, Annie; Pförtner, Timo-Kolja; White, James; Pickett, Kate E

    2016-03-01

    Research on socioeconomic differences in overweight and obesity and on the ecological association between income inequality and obesity prevalence suggests that relative deprivation may contribute to lifestyle risk factors for obesity independently of absolute affluence. We tested this hypothesis using data on 25,980 adolescents (11-15 years) in the 2010 Canadian Health Behaviour in School-aged Children (HBSC) study. The Yitzhaki index of relative deprivation was applied to the HBSC Family Affluence Scale, an index of common material assets, with more affluent schoolmates representing the comparative reference group. Regression analysis tested the associations between relative deprivation and four obesity risk factors (skipping breakfasts, physical activity, and healthful and unhealthful food choices) plus dietary restraint. Relative deprivation uniquely related to skipping breakfasts, less physical activity, fewer healthful food choices (e.g., fruits, vegetables, whole grain breads), and a lower likelihood of dieting to lose weight. Consistent with Runciman's (1966) theory of relative deprivation and with psychosocial interpretations of the health consequences of income inequality, the results indicate that having mostly better off schoolmates can contribute to poorer health behaviours independently of school-level affluence and subjective social status. We discuss the implications of these findings for understanding the social origins of obesity and targeting health interventions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Increased relative risk of myelodysplastic syndrome in atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Oda, Kenji [Hiroshima City Hospital (Japan); Kimura, Akiro; Matsuo, Tatsuki; Tomonaga, Masao; Kodama, Kazunori; Mabuchi, Kiyohiko

    1998-12-01

    It was investigated what blood disorders except leukemia increased the relative risk with dose dependency in atomic bomb survivors. Subjects were 217 patients of atomic bomb survivors in Hiroshima and Nagasaki, who had blood disorders except leukemia and died between 1950 and 1990. Their medical records were analyzed and their diagnoses were reevaluated. Sixteen cases were diagnosed as the aplastic anemia and 12 as the myelodysplastic syndrome (MDS). In the aplastic anemia, there was no correlation between the exposure dose and the mortality. In MDS, the excess relative risk (ERR)/bone marrow exposure dose of 1 Sv was very high (13.0). These results supports the hypothesis that MDS would be broken out by the clonal abnormality of the hematopoietic stem cell and radiation exposure could cause the appearance of the abnormal stem cell clone. (K.H.)

  18. Update on procedure-related risks for prenatal diagnosis techniques

    DEFF Research Database (Denmark)

    Tabor, Ann; Alfirevic, Zarko

    2010-01-01

    Introduction: As a consequence of the introduction of effective screening methods, the number of invasive prenatal diagnostic procedures is steadily declining. The aim of this review is to summarize the risks related to these procedures. Material and Methods: Review of the literature. Results: Data...... from randomised controlled trials as well as from systematic reviews and a large national registry study are consistent with a procedure-related miscarriage rate of 0.5-1.0% for amniocentesis as well as for chorionic villus sampling (CVS). In single-center studies performance may be remarkably good due...... not be performed before 15 + 0 weeks' gestation. CVS on the other hand should not be performed before 10 weeks' gestation due to a possible increase in risk of limb reduction defects. Discussion: Experienced operators have a higher success rate and a lower complication rate. The decreasing number of prenatal...

  19. Development of a prediction model and estimation of cumulative risk for upper aerodigestive tract cancer on the basis of the aldehyde dehydrogenase 2 genotype and alcohol consumption in a Japanese population

    Science.gov (United States)

    Koyanagi, Yuriko N.; Ito, Hidemi; Oze, Isao; Hosono, Satoyo; Tanaka, Hideo; Abe, Tetsuya; Shimizu, Yasuhiro; Hasegawa, Yasuhisa

    2017-01-01

    Alcohol consumption and the aldehyde dehydrogenase 2 (ALDH2) polymorphism are associated with the risk of upper aerodigestive tract cancer, and a significant gene–environment interaction between the two has been confirmed in a Japanese population. To aid the development of a personalized prevention strategy, we developed a risk-prediction model and estimated absolute risks stratified by a combination of the ALDH2 genotype and alcohol consumption. We carried out two age-matched and sex-matched case–control studies: one (630 cases and 1260 controls) for model derivation and the second (654 cases and 654 controls) for external validation. On the basis of data from the derivation study, a prediction model was developed by fitting a conditional logistic regression model using the following predictors: age, sex, smoking, drinking, and the ALDH2 genotype. The risk model, including a combination of the ALDH2 genotype and alcohol consumption, provided high discriminatory accuracy and good calibration in both the derivation and the validation studies: C statistics were 0.82 (95% confidence interval 0.80–0.84) and 0.83 (95% confidence interval 0.81–0.85), respectively, and the calibration plots of both studies remained close to the ideal calibration line. Cumulative risks were obtained by combining odds ratios estimated from the risk model with the age-specific incidence rate and population size. For heavy drinkers with a heterozygous genotype, the cumulative risk at age 80 was above 20%. In contrast, risk in the other groups was less than 5%. In conclusion, modification of alcohol consumption according to the ALDH2 genotype will have a major impact on upper aerodigestive tract cancer prevention. These findings represent a simple and practical model for personalized cancer prevention. PMID:26862830

  20. Population-based prevalence of cervical infection with human papillomavirus genotypes 16 and 18 and other high risk types in Tlaxcala, Mexico.

    Science.gov (United States)

    Rudolph, Samantha E; Lorincz, Attila; Wheeler, Cosette M; Gravitt, Patti; Lazcano-Ponce, Eduardo; Torres-Ibarra, Leticia; León-Maldonado, Leith; Ramírez, Paula; Rivera, Berenice; Hernández, Rubí; Franco, Eduardo L; Cuzick, Jack; Méndez-Hernández, Pablo; Salmerón, Jorge

    2016-09-01

    Cervical cancer remains an important cause of cancer mortality for Mexican women. HPV 16/18 typing may help to improve cervical cancer screening. Here we present the prevalence of high-risk human papillomavirus (hrHPV) including HPV16 and HPV18 from the FRIDA (Forwarding Research for Improved Detection and Access) population. Beginning in 2013, we recruited 30,829 women aged 30-64 in Tlaxcala, Mexico. Cervical samples were collected and tested for 14 hrHPV genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). We used logistic regression to estimate odds ratios with 95 % confidence intervals for hrHPV infections according to putative risk factors. Prevalence of infection with any of the 14 hrHPV types was 11.0 %. The age-specific prevalence of all hrHPV formed a U-shaped curve with a higher prevalence for women aged 30-39 and 50-64 than women aged 40-49. Across all age groups, 2.0 % of women were positive for HPV16 and/or HPV18 (HPV16/18), respectively. HPV16/18 prevalence also showed a U-shaped curve with increased prevalence estimates for women aged both 30-39 and 60-64. Both prevalence curves had a significant quadratic age coefficient. Infections with hrHPV were positively associated with an increased number of lifetime sexual partners, a history of sexually transmitted disease, being unmarried, use of hormonal contraception, having a history of smoking and reported condom use in the multivariate model. The FRIDA population has a bimodal distribution of both hrHPV and HPV16/18 positivity with higher prevalences at ages 30-39 and 60-64. These findings will help to evaluate triage algorithms based on HPV genotyping. The trial is registered with ClinicalTrials.gov, number NCT02510027 .

  1. Estimating relative risks for common outcome using PROC NLP.

    Science.gov (United States)

    Yu, Binbing; Wang, Zhuoqiao

    2008-05-01

    In cross-sectional or cohort studies with binary outcomes, it is biologically interpretable and of interest to estimate the relative risk or prevalence ratio, especially when the response rates are not rare. Several methods have been used to estimate the relative risk, among which the log-binomial models yield the maximum likelihood estimate (MLE) of the parameters. Because of restrictions on the parameter space, the log-binomial models often run into convergence problems. Some remedies, e.g., the Poisson and Cox regressions, have been proposed. However, these methods may give out-of-bound predicted response probabilities. In this paper, a new computation method using the SAS Nonlinear Programming (NLP) procedure is proposed to find the MLEs. The proposed NLP method was compared to the COPY method, a modified method to fit the log-binomial model. Issues in the implementation are discussed. For illustration, both methods were applied to data on the prevalence of microalbuminuria (micro-protein leakage into urine) for kidney disease patients from the Diabetes Control and Complications Trial. The sample SAS macro for calculating relative risk is provided in the appendix.

  2. Fibronectin gene polymorphisms and clinical manifestations of mixed cryoglobulinemic syndrome: increased risk of lymphoma associated to MspI DD and HaeIII AA genotypes

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    C. Fabro

    2011-09-01

    Full Text Available Objective: To analyse FN gene polymorphisms in type II mixed cryoglobulinemic syndrome (MCsn, an immune-complex mediated systemic vasculitis linked to hepatitis C virus (HCV infection and characterized by rheumatoid factor (RF positive B-cell proliferation at high risk for the progression into non Hodgkin’s lymphoma (NHL. Methods: Samples from eighty-one patients, with MCsn (type II serum cryoglobulins and clinical signs of vasculitis were studied. Sixthy-five (65/81, 80.3% patients were HCV-positive. Twenty-one (25.9% patients had developed a B-cell NHL during the course of MCsn. Seventy-two patients with HCV-negative and MC-unrelated NHL and 110 healthy blood donors (HBDs were taken as controls. HaeIIIb and MspI FN gene polymorphisms were analysed by PCR and specific restriction enzyme digestions, following reported procedures. Plasma FN levels were analysed by ELISA, whenever possible. Results: HaeIIIb and MspI allele and genotype frequencies did not differ between MCsn patients and HBDs. Of note, the DD-MspI (OR=5.56; CI=1.67-18.51, p=0.0046 and the AA-HaeIIIb (OR=5.54; CI=1.64-18.76, p=0.0066 homozygosis appeared significantly and independently associated with the development of B-cell NHL in MCsn patients, with the HaeIIIb A allele possibly conferring an increased risk of NHL in the general population (OR=1.72, CI=1.128- 2.635, p=0.0133. In contrast, the major vasculitic manifestations, such as peripheral neuropathy, skin ulcers and glomerulonephritis tended to be associated with the counterpart MspI C allele. No association between FN plasma levels and FN genotypes was found. Conclusion: Genotyping for MspI and HaeIIIb FN gene polymorphisms may be clinically relevant to define the predisposition to the major clinical manifestations in MCsn.

  3. Prevalence, risk factors and genotypes of hepatitis B infection among HIV-infected patients in the State of MS, Central Brazil

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    Solange Zacalusni Freitas

    Full Text Available Objectives: A cross-sectional study on prevalence of HBV and HDV infection, risk factors and genotype distribution of HBV infection was conducted among 848 HIV-infected patients in Mato Grosso do Sul, Central Brazil. Methods: Serum samples of 848 participants were tested for hepatitis B surface antigen (HBsAg, hepatitis B core antibody (anti-HBc and hepatitis surface antibody (anti-HBs. HBsAg positive samples were tested for anti-HBc IgM, HBeAg, anti-HBe, anti-HCV, and total anti-HDV. HBsAg and anti-HBc positive were subjected to DNA extraction. Viral DNA was amplified by semi-nested PCR for the regions pre-S/S and then purified and genotyped/subgenotyped by direct sequencing. Student's t-test, chi-square test and Fisher's exact test were used to compare variables and to evaluate association between HBV positivity (defined as anti-HBc and/or HBsAg positivity and risk factors. Results: Among the 848 HIV infected patients investigated 222 had serological markers of HBV infection. The prevalence rate of HIV-HBV coinfection was 2.5% (21/848; 95% CI: 1.4–3.5%; 484 (57.1% patients were susceptible for HBV infection. There were no cases of anti-HDV positive and only one (0.1% anti-HCV-positive case among the HIV-HBV coinfected patients. Male gender, increasing age, family history of hepatitis, use of illicit drug, and homosexual activity were independent factors associated with HBV exposure. The phylogenetic analysis based on the S gene region revealed the presence of genotypes D (76.9%, F (15.4% and A (7.7% in the study sample. Conclusion: This study demonstrates the low prevalence of HIV-HBV infection and also highlights the need for early vaccination against HBV as well as testing for HBV, HCV and HDV in all HIV-infected individuals.

  4. The variant of pri-mir-26a-1 polymorphism is associated with decreased risk of betel quid-related oral premalignant lesions and oral squamous cell carcinoma.

    Science.gov (United States)

    Yang, Cheng-Mei; Chen, Chien-Chou; Tseng, Yu-Kai; Huang, Sin-Jhih; Liou, Huei-Han; Lee, Yi-Cheng; Lee, Jang-Hwa; Wang, Jyh-Seng; Chen, Hung-Chih; Chi, Chao-Chuan; Kang, Bor-Hwang; Lin, Yun-Chung; Tsai, Kuo-Wang; Ger, Luo-Ping

    2017-06-08

    This case-control study evaluated the association of the single nucleotide polymorphism rs7372209 (T>C) in pri-mir-26a-1 with the risk and progression of betel quid (BQ)-related oral premalignant lesions (OPLs) and oral squamous cell carcinoma (OSCC). In total, 597 BQ chewers were recruited: 196 healthy controls, 241 patients with OPLs, and 160 patients with OSCC. Genotypes were determined using the TaqMan real-time assay. The C/T + T/T genotypes and T allele in pri-mir-26a-1 were correlated with a decreased risk of BQ-related OPLs (P = .038 and .005, respectively), oral leukoplakia (P = .01 and .001, respectively), and advanced-stage OSCC (P = .021 and .004, respectively). The effects of the C/T + T/T genotypes and T allele on the decreased risk of OPLs were potent in the older age group (both Pinteraction pri-mir-26a-1 may have a decreased risk of oral leukoplakia, OPLs, and advanced-stage OSCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

    Science.gov (United States)

    Cameron, D Joshua; Yang, Zhenglin; Gibbs, Daniel; Chen, Haoyu; Kaminoh, Yuuki; Jorgensen, Adam; Zeng, Jiexi; Luo, Ling; Brinton, Eric; Brinton, Gregory; Brand, John M; Bernstein, Paul S; Zabriskie, Norman A; Tang, Shibo; Constantine, Ryan; Tong, Zongzhong; Zhang, Kang

    2007-05-02

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better understand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.

  6. Urbanization and traffic related exposures as risk factors for Schizophrenia

    DEFF Research Database (Denmark)

    Pedersen, Carsten Bøcker; Mortensen, Preben Bo

    2006-01-01

    that traffic related exposures affect schizophrenia risk and that this potential effect is responsible for the urban-rural differences. The geographical distance from place of residence to nearest major road was used as a proxy variable for traffic related exposures. We used a large population-based sample...... of the Danish population (1.89 million people) including information on all permanent addresses linked with geographical information on all roads and house numbers in Denmark. Schizophrenia in cohort members (10,755 people) was identified by linkage with the Danish Psychiatric Central Register. RESULTS...

  7. Modelling the genetic risk in age-related macular degeneration.

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    Felix Grassmann

    Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

  8. Relation of anthropometric variables to coronary artery disease risk factors

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    Virendra C Patil

    2011-01-01

    Full Text Available Background and Objectives: Anthropometric variables and their relation to conventional coronary artery disease (CAD risk factors in railway employees have been inadequately studied in India. This cross-sectional survey was carried out in the Solapur division of the Central railway in the year 2004, to assess the anthropometric variables in railway employees and their relation to conventional CAD risk factors. Materials and Methods: A total of 995 railway employees, with 872 males and 123 females participated in this cross-sectional study. All subjects underwent anthropometric measurements, fasting lipid profile, and blood sugar level. Various anthropometric indices were calculated for body mass index (BMI, waist circumference (WC, waist-to-hip ratio (WHR, waist-to-height ratio (WHtR, and abdominal volume index (AVI. Statistical analysis was done by EPI Info 6 statistical software. Results: Compared to all other obesity indices, WHtR was most prevalent in both genders. High WHtR was present in 699 (80.16% males and 103 (83.73% females. Age ≥45 years, high systolic BP, high diastolic BP, low HDL, high triglyceride, and diabetes mellitus were positively correlated with high BMI, high WC, high WHR, high WHtR, and high AVI. High BMI, high WC, high WHR, high WHtR, and high AVI were negatively associated with physical inactivity. Conclusions: Over all, anthropometric variables in both genders were significantly deranged in subjects with coronary risk factors. Compared to all other anthropometric variables, WHtR was statistically significantly associated with a majority of coronary artery risk factors. Hence we recommend inclusion of WHtR as a parameter of obesity to predict coronary artery disease risk factor along with WC, WHR, and BMI in epidemiologic studies.

  9. Genotype of 168 child cases with high-risk thalassemia%168例高危地中海贫血儿童基因谱分析

    Institute of Scientific and Technical Information of China (English)

    刘宁毅

    2013-01-01

    Objective To analyze the genotypes of high-risk thalassemia (thalassemia) children.Methods Samples were collected from 168 children with high-risk thalassemia and the genotypes of α-thalassemia and β-thalassemia were detected.The α-thalassemia cases were detected for three alpha deletion genotypes (-SEA/-a 3.7/-a 4.2) and three non-deletion mutant α-thalassemia (HbCS HbQS HbWS).The alpha deletion genotype was detected with single-tube multiplex PCR technology,non-deletion mutant α-thalassemia and β-thalassemia (17 sites) in common Chinese people were detected with by using reverse dot blot hybridization.Results Totally 49 o-thalassemia cases were detected from 168 children at high risk of thalassemia,accounted for 29.17% ;including 39 deletion α-thalassemia cases,accounting for 79.59% of the alpha-thalassemia cases,10 non-deletion mutant a-thalassemia cases,accounting for 20.41% of α-thalassemia.Twenty-seven deletion β-thalassemia cases were detected accounting for 16.07%; including double heterozygotes in 5 cases,accounting for 2.98% ; detection composite α β-groundpoor in 12 cases,accounting for 7.14%; the total detection rate was 55.36%.Conclusions The incidence of thalassemia in Qinzhou is high,and large-scale screening of thalassemia among population of child-bearing age is indicated for improvement of prenatal care and reduce the incidence of thalassemia ion Qinzhou.%目的 应用基因诊断技术探讨高危地中海贫血(地贫)儿童的常见基因谱的分布特征. 方法 用钦州地区168例高危地贫的儿童样本分别检测α-地贫及β-地贫基因型,而α-地贫分为3种d缺失型基因检测(-SEA/,-α 3.7/-α4.2)和3种非缺失突变型仅地贫(HbCS,HbQS,HbWS).α缺失型基因检测应用单管多重PCR技术进行检测,非缺失突变型α地贫和β-地贫(检测中国人常见的17种位点)均采用反向斑点杂交法. 结果 在168例进行地贫基因检查的钦州地区高危地

  10. Health status of cardiac genetic disease patients and their at-risk relatives.

    Science.gov (United States)

    Ingles, Jodie; Yeates, Laura; Hunt, Lauren; McGaughran, Julie; Scuffham, Paul A; Atherton, John; Semsarian, Christopher

    2013-05-25

    Health status is an important outcome measure that incorporates multiple dimensions of health, including symptoms, functional status, and psychosocial factors. While health status has been shown to be a predictor for hospital readmission, morbidity and mortality in the heart failure setting, there are limited data in cardiac genetic disease. We examined health status in a number of cardiac genetic disease groups compared to the general Australian population. A total of 409 individuals were assessed. Individuals with inherited cardiomyopathies [hypertrophic cardiomyopathy (HCM), familial dilated cardiomyopathy (FDC), arrhythmogenic right ventricular cardiomyopathy (ARVC)] and primary arrhythmogenic disorders [long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT)], as well as their first-degree relatives, completed the Medical Outcomes Survey Short Form-36 (SF-36). The physical and mental component scores (PCS and MCS) and SF-6D utility score were assessed. Patients with HCM (p<0.001), FDC (p<0.05), and CPVT (p<0.05) were found to have a significantly lower PCS, while patients with LQTS (p<0.01) had a lower MCS. Individuals at risk of HCM (p<0.0001) and genotype positive-phenotype negative HCM patients (p<0.01) both had a higher PCS and utility scores compared to the clinically affected HCM population. Individuals at risk of LQTS had significantly higher PCS than those with a clinical diagnosis of LQTS (p<0.05) and similarly individuals at risk of FDC had significantly higher PCS than FDC patients (p<0.05). In HCM, female gender (p=0.002), presence of co-morbidities (p<0.0001) and higher NYHA functional class (p<0.0001) were predictors of a lower PCS. Patients with a clinical diagnosis of a genetic heart disease have an impaired health status, related to both physical and mental function. Clinical management strategies in such patient groups need to consider health status as an important outcome measure. Copyright © 2011 Elsevier

  11. Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The Tromso Study.

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    Rolf Jorde

    Full Text Available OBJECTIVE: Low serum 25(OHD levels are associated with cardiovascular risk factors, and also predict future myocardial infarction (MI, type 2 diabetes (T2DM, cancer and all-cause mortality. Recently several single nucleotide polymorphisms (SNPs associated with serum 25-hydroxyvitamin D (25(OHD level have been identified. If these relations are causal one would expect a similar association between these SNPs and health. METHODS: DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints MI, T2DM, cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2007-2010. Genotyping was performed for 17 SNPs related to the serum 25(OHD level. RESULTS: A total of 9528 subjects were selected for genetic analyses which were successfully performed for at least one SNP in 9471 subjects. Among these, 2025 were registered with MI, 1092 with T2DM, 2924 with cancer and 3828 had died. The mean differences in serum 25(OHD levels between SNP genotypes with the lowest and highest serum 25(OHD levels varied from 0.1 to 7.8 nmol/L. A genotype score based on weighted risk alleles regarding low serum 25(OHD levels was established. There was no consistent association between the genotype score or individuals SNPs and MI, T2DM, cancer, mortality or risk factors for disease. However, for rs6013897 genotypes (located at the 24-hydroxylase gene (CYP24A1 there was a significant association with breast cancer (P<0.05. CONCLUSION: Our results do not support nor exclude a causal relationship between serum 25(OHD levels and MI, T2DM, cancer or mortality, and our observation on breast cancer needs confirmation. Further genetic studies are warranted, particularly in populations with vitamin D deficiency. TRIAL REGISTRATION: ClinicalTrials.gov NCT01395303.

  12. Investigation of morphine and morphine glucuronide levels and cytochrome P450 isoenzyme 2D6 genotype in codeine-related deaths.

    Science.gov (United States)

    Frost, Joachim; Helland, Arne; Nordrum, Ivar S; Slørdal, Lars

    2012-07-10

    Compared to morphine and morphine-6-glucuronide (M6G), codeine and its other major metabolites codeine-6-glucuronide and norcodeine have weak affinity to opioid μ-receptors. Analgesic effects of codeine are thus largely dependent on metabolic conversion to morphine by the polymorphic cytochrome P450 isoenzyme 2D6 (CYP2D6). How this relates to toxicity and post-mortem whole blood levels is not known. This paper presents a case series of codeine-related deaths where concentrations of morphine, M6G and morphine-3-glucuronide (M3G), as well as CYP2D6 genotype, are taken into account. Post-mortem toxicological specimens from a total of 1444 consecutive forensic autopsy cases in Central Norway were analyzed. Among these, 111 cases with detectable amounts of codeine in femoral blood were identified, of which 34 had femoral blood concentrations exceeding the TIAFT toxicity threshold of 0.3mg/L. Autopsy records of these 34 cases were retrieved and reviewed. In the 34 reviewed cases, there was a large variability in individual morphine to codeine concentration ratios (M/C ratios), and morphine levels could not be predicted from codeine concentrations, even when CYP2D6 genotype was known. 13 cases had codeine concentrations exceeding the TIAFT threshold for possibly lethal serum concentrations (1.6 mg/L). Among these, 8 individuals had morphine concentrations below the toxic threshold according to TIAFT (0.15 mg/L). In one case, morphine as well as M6G and M3G concentrations were below the limit of detection. A comprehensive investigation of codeine-related fatalities should, in addition to a detailed case history, include quantification of morphine and morphine metabolites. CYP2D6 genotyping may be of interest in cases with unexpectedly high or low M/C ratios.

  13. Risk Factors in Normal-Tension Glaucoma and High-Tension Glaucoma in relation to Polymorphisms of Endothelin-1 Gene and Endothelin-1 Receptor Type A Gene

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    Dominika Wróbel-Dudzińska

    2015-01-01

    Full Text Available The aim of the research is to analyse the influence of polymorphisms of endothelin-1 gene and endothelin-1 receptor type A gene on the clinical condition of patients with primary open angle glaucoma. Methods. 285 Polish patients took part in the research (160 normal-tension glaucoma and 125 high-tension glaucoma. DNA was isolated by standard methods and genotype distributions of four polymorphisms in genes encoding endothelin-1 (K198N and endothelin-1 receptor type A polymorphisms (C1222T, C70G, and G231A were determined. Genotype distributions were compared between NTG and HTG groups. The clinical condition of participants was examined for association with polymorphisms. Results. A similar frequency of occurrence of the polymorphic varieties of the studied genes was observed in patients with NTG and HTG. There is no relation between NTG risk factors and examined polymorphisms. NTG patients with TT genotype of K198N polymorphism presented with the lowest intraocular pressure in comparison to GG + GT genotype (p=0.03. In NTG patients with CC genotype of C1222T polymorphism (p=0.028 and GG of C70G polymorphism (p=0.03 the lowest values of mean blood pressure were observed. Conclusions. The studied polymorphic varieties (K198N, C1222T do have an influence on intraocular pressure as well as arterial blood pressure in NTG patients.

  14. Nanotechnology, risk, and oversight: learning lessons from related emerging technologies.

    Science.gov (United States)

    Kuzma, Jennifer; Priest, Susanna

    2010-11-01

    Emerging technologies are defined by their novelty and thus are accompanied by significant uncertainty in determining appropriate ways to manage risks associated with them. Yet, there is a body of prior knowledge about risk management and oversight policy for other technologies that have already permeated society. Here, we describe two ways in which prospective oversight policy analysis for emerging technologies can draw upon these past experiences. One involves comparing specific products that have already been marketed to similar products of the emerging technology (cognate-product approach). The other treats the emerging technology as a body of products and methods and relates it to another technological field that has already emerged and penetrated markets (whole-technology approach). In this article, we describe our work using these approaches to inform risk and oversight policy for nanotechnology and its products. We draw parallels between biotechnology and nanotechnology as whole fields of development and also between genetically engineered organisms in the food supply and agricultural products of nanotechnology. Through these comparisons, we find that both approaches to historical learning have value and present lessons that could be applied to nanotechnology. © 2010 Society for Risk Analysis.

  15. Relative radiological risks derived from different TENORM wastes in Malaysia.

    Science.gov (United States)

    Ismail, B; Teng, I L; Muhammad Samudi, Y

    2011-11-01

    In Malaysia technologically enhanced naturally occurring radioactive materials (TENORM) wastes are mainly the product of the oil and gas industry and mineral processing. Among these TENORM wastes are tin tailing, tin slag, gypsum and oil sludge. Mineral processing and oil and gas industries produce large volume of TENORM wastes that has become a radiological concern to the authorities. A study was carried out to assess the radiological risk related to workers working at these disposal sites and landfills as well as to the members of the public should these areas be developed for future land use. Radiological risk was assessed based on the magnitude of radiation hazard, effective dose rates and excess cancer risks. Effective dose rates and excess cancer risks were estimated using RESRAD 6.4 computer code. All data on the activity concentrations of NORM in wastes and sludges used in this study were obtained from the Atomic Energy Licensing Board, Malaysia, and they were collected over a period of between 5 and 10 y. Results obtained showed that there was a wide range in the total activity concentrations (TAC) of nuclides in the TENORM wastes. With the exception of tin slag and tin tailing-based TENORM wastes, all other TENORM wastes have TAC values comparable to that of Malaysia's soil. Occupational Effective Dose Rates estimated in all landfill areas were lower than the 20 mSv y(-1) permissible dose limit. The average Excess Cancer Risk Coefficient was estimated to be 2.77×10(-3) risk per mSv. The effective dose rates for residents living on gypsum and oil sludge-based TENORM wastes landfills were estimated to be lower than the permissible dose limit for members of the public, and was also comparable to that of the average Malaysia's ordinary soils. The average excess cancer risk coefficient was estimated to be 3.19×10(-3) risk per mSv. Results obtained suggest that gypsum and oil sludge-based TENORM wastes should be exempted from any radiological regulatory

  16. Diversity in the carotenoid profiles and the expression of genes related to carotenoid accumulation among citrus genotypes.

    Science.gov (United States)

    Ikoma, Yoshinori; Matsumoto, Hikaru; Kato, Masaya

    2016-01-01

    Carotenoids are not only important to the plants themselves but also are beneficial to human health. Since citrus fruit is a good source of carotenoids for the human diet, it is important to study carotenoid profiles and the accumulation mechanism in citrus fruit. Thus, in the present paper, we describe the diversity in the carotenoid profiles of fruit among citrus genotypes. In regard to carotenoids, such as β-cryptoxanthin, violaxanthin, lycopene, and β-citraurin, the relationship between the carotenoid profile and the expression of carotenoid-biosynthetic genes is discussed. Finally, recent results of quantitative trait locus (QTL) analyses of carotenoid contents and expression levels of carotenoid-biosynthetic genes in citrus fruit are shown.

  17. Comparison of Fasciola hepatica genotypes in relation to their ability to establish patent infections in the final host.

    Science.gov (United States)

    Zintl, Annetta; Talavera, Silvia; Sacchi-Nestor, Carlotta; Ryan, Marion; Chryssafidis, Andreas; Mulcahy, Grace

    2015-06-15

    Fasciola hepatica is a common and economically important parasite of sheep and cattle. Although its marked genetic heterogeneity is well recognised, an association between haplotypes and specific phenotypic traits has yet to be identified. Using experimental infections in cattle this study investigated whether a fragment of mitochondrial DNA (coding for cytochrome c oxidase subunit III, transfer RNA histidine and cytochrome b) and 3 nuclear microsatellite loci (Fh15, Fh23 and Fh25) could be used as markers for the parasite's ability to complete its tissue migration and establish in the liver of the final host. While we did not detect any shift in the frequency of the various genotypes in the population of metacercariae used for the infection on the one hand and the flukes collected from the liver on the other, there was an indication that parasites with heterozygous microsatellite alleles may have a selective advantage over homozygote parasites during their migration in the final host.

  18. 4G/4G Genotype of PAI-1 Gene Is Associated With Reduced Risk of Stroke in Elderly

    NARCIS (Netherlands)

    Hoekstra, T.; Geleijnse, J.M.; Kluft, C.; Giltay, E.J.; Kok, F.J.; Schouten, E.G.

    2003-01-01

    Background and Purpose - Plasminogen activator inhibitor type 1 ( PAI- 1) is the main inhibitor of fibrinolysis, and high levels may increase the risk of cardiovascular disease. The 4G/ 5G polymorphism affects PAI- 1 gene transcription with lower levels of plasma PAI- 1 in the presence of the 5G

  19. 4G/4G Genotype of PAI-1 Gene Is Associated With Reduced Risk of Stroke in Elderly

    NARCIS (Netherlands)

    Hoekstra, T.; Geleijnse, J.M.; Kluft, C.; Giltay, E.J.; Kok, F.J.; Schouten, E.G.

    2003-01-01

    Background and Purpose - Plasminogen activator inhibitor type 1 ( PAI- 1) is the main inhibitor of fibrinolysis, and high levels may increase the risk of cardiovascular disease. The 4G/ 5G polymorphism affects PAI- 1 gene transcription with lower levels of plasma PAI- 1 in the presence of the 5G all

  20. AT1 mutations and risk of atrial fibrillation based on genotypes from 71,000 individuals from the general population

    DEFF Research Database (Denmark)

    Marott, S C W; Nordestgaard, B G; Jensen, G B

    2013-01-01

    % CI: 1.6-4.2) for men. CONCLUSIONS: Heterozygosity for the non-synonymous AT(1) genetic variants A244S and I103T/A244S associated with increased risk of atrial fibrillation in men. The AT(1) might be a target for the pharmaceutical industry. This finding needs to be validated in independent studies....

  1. 4G/4G Genotype of PAI-1 Gene Is Associated With Reduced Risk of Stroke in Elderly

    NARCIS (Netherlands)

    Hoekstra, T.; Geleijnse, J.M.; Kluft, C.; Giltay, E.J.; Kok, F.J.; Schouten, E.G.

    2003-01-01

    Background and Purpose - Plasminogen activator inhibitor type 1 ( PAI- 1) is the main inhibitor of fibrinolysis, and high levels may increase the risk of cardiovascular disease. The 4G/ 5G polymorphism affects PAI- 1 gene transcription with lower levels of plasma PAI- 1 in the presence of the 5G all

  2. Evaluation of Risk Factors Related to Recidivism Among Sentenced Males

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    Sinem Yıldız

    2011-12-01

    Full Text Available Risk assessment is taking the place of dangerousness in recent criminal research. Detection of static and dynamic risk factors related and/or interacting to recidivism in accordance with personality characteristics and crime types may help crime prevention strategies to improve. Out of all participants 35% (n=41 are sentenced for manslaughter/physical injury, 35% (n=41 sexual crime and 30% (n=35 theft. The mean age of the participants is 33.81 (sd=9-12 years. During the interview, a questionnaire which is prepared by the researcher by reviewing the literature, Symptom Checklist Short Form, aggression inventory was used. Interviews are conducted face to face by the researcher at the relevant correctional facilities with the permissions of Ministry of Justice and ethical committee. Recidivism is found related to having a period far away from nuclear family before age 18, criminal and drag-alcohol abusing friends, anti-social behaviors; abusing illegal drags, displaying disciplinary problems in prison and during military service. Discussion: Results are evaluated under demographics, relationships in family and close friends, childhood abuse by leaning on current literature. Key words: prevention and control, crime, risk assessment

  3. Aerobic exercise reduces biomarkers related to cardiovascular risk among cleaners

    DEFF Research Database (Denmark)

    Korshøj, Mette; Ravn, Marie Højbjerg; Holtermann, Andreas;

    2016-01-01

    PURPOSE: Blue-collar workers have an increased risk of cardiovascular disease. Accordingly, elevated levels of biomarkers related to risk of cardiovascular disease, such as high-sensitive C-reactive protein, have been observed among blue-collar workers. The objective was to examine whether....... The reference group (n = 59) received lectures, and the aerobic exercise group (n = 57) performed worksite aerobic exercise (30 min twice a week). Levels of biomarkers (high-sensitive C-reactive protein, fibrinogen, cholesterol, low- and high-density lipoprotein cholesterol and triglyceride) were collected...... at baseline and after 4 months. A repeated-measure, multi-adjusted, mixed-model intention-to-treat analysis was applied to compare between-group differences. The study was registered as ISRCTN86682076. RESULTS: Significant (p high...

  4. MicroRNA Related Polymorphisms and Breast Cancer Risk

    Science.gov (United States)

    Khan, Sofia; Greco, Dario; Michailidou, Kyriaki; Milne, Roger L.; Muranen, Taru A.; Heikkinen, Tuomas; Aaltonen, Kirsimari; Dennis, Joe; Bolla, Manjeet K.; Liu, Jianjun; Hall, Per; Irwanto, Astrid; Humphreys, Keith; Li, Jingmei; Czene, Kamila; Chang-Claude, Jenny; Hein, Rebecca; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fletcher, Olivia; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Gibson, Lorna; Aitken, Zoe; Hopper, John L.; Tsimiklis, Helen; Bui, Minh; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Apicella, Carmel; Stone, Jennifer; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A.; van der Luijt, Rob B.; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Turnbull, Clare; Rahman, Nazneen; Chanock, Stephen J.; Hunter, David J.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Schmidt, Marjanka K.; Broeks, Annegien; Veer, Laura J. V. a. n't.; Hogervorst, Frans B.; Fasching, Peter A.; Schrauder, Michael G.; Ekici, Arif B.; Beckmann, Matthias W.; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Benitez, Javier; Zamora, Pilar M.; Perez, Jose I. A.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Pharoah, Paul D. P.; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Brown, Judith; Couch, Fergus J.; Wang, Xianshu; Vachon, Celine; Olson, Janet E.; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Mulot, Claire; Marme, Frederick; Burwinkel, Barbara; Schneeweiss, Andreas; Sohn, Christof; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Andrulis, Irene L.; Knight, Julia A.; Tchatchou, Sandrine; Mulligan, Anna Marie; Dörk, Thilo; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Anton-Culver, Hoda; Darabi, Hatef; Eriksson, Mikael; Garcia-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; van Asperen, Christi J.; Kristensen, Vessela N.; Slager, Susan; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Lindblom, Annika; Margolin, Sara; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Mariani, Paolo; Hooning, Maartje J.; Martens, John W. M.; Collée, J. Margriet; Jager, Agnes; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Giles, Graham G.; McLean, Catriona; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Mannermaa, Arto; Hamann, Ute; Chenevix-Trench, Georgia; Blomqvist, Carl; Aittomäki, Kristiina; Easton, Douglas F.; Nevanlinna, Heli

    2014-01-01

    Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88–0.96), rs1052532 (OR 0.97; 95% CI: 0.95–0.99), rs10719 (OR 0.97; 95% CI: 0.94–0.99), rs4687554 (OR 0.97; 95% CI: 0.95–0.99, and rs3134615 (OR 1.03; 95% CI: 1.01–1.05) located in the 3′ UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects. PMID:25390939

  5. MicroRNA related polymorphisms and breast cancer risk.

    Directory of Open Access Journals (Sweden)

    Sofia Khan

    Full Text Available Genetic variations, such as single nucleotide polymorphisms (SNPs in microRNAs (miRNA or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS. Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC. Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR 0.92; 95% confidence interval (CI: 0.88-0.96, rs1052532 (OR 0.97; 95% CI: 0.95-0.99, rs10719 (OR 0.97; 95% CI: 0.94-0.99, rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05 located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

  6. MicroRNA related polymorphisms and breast cancer risk.

    Science.gov (United States)

    Khan, Sofia; Greco, Dario; Michailidou, Kyriaki; Milne, Roger L; Muranen, Taru A; Heikkinen, Tuomas; Aaltonen, Kirsimari; Dennis, Joe; Bolla, Manjeet K; Liu, Jianjun; Hall, Per; Irwanto, Astrid; Humphreys, Keith; Li, Jingmei; Czene, Kamila; Chang-Claude, Jenny; Hein, Rebecca; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fletcher, Olivia; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Gibson, Lorna; Aitken, Zoe; Hopper, John L; Tsimiklis, Helen; Bui, Minh; Makalic, Enes; Schmidt, Daniel F; Southey, Melissa C; Apicella, Carmel; Stone, Jennifer; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A; van der Luijt, Rob B; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Turnbull, Clare; Rahman, Nazneen; Chanock, Stephen J; Hunter, David J; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Schmidt, Marjanka K; Broeks, Annegien; Van't Veer, Laura J; Hogervorst, Frans B; Fasching, Peter A; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Benitez, Javier; Zamora, Pilar M; Perez, Jose I A; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Pharoah, Paul D P; Dunning, Alison M; Shah, Mitul; Luben, Robert; Brown, Judith; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Olson, Janet E; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Mulot, Claire; Marme, Frederick; Burwinkel, Barbara; Schneeweiss, Andreas; Sohn, Christof; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Andrulis, Irene L; Knight, Julia A; Tchatchou, Sandrine; Mulligan, Anna Marie; Dörk, Thilo; Bogdanova, Natalia V; Antonenkova, Natalia N; Anton-Culver, Hoda; Darabi, Hatef; Eriksson, Mikael; Garcia-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; van Asperen, Christi J; Kristensen, Vessela N; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Lindblom, Annika; Margolin, Sara; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Mariani, Paolo; Hooning, Maartje J; Martens, John W M; Collée, J Margriet; Jager, Agnes; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Giles, Graham G; McLean, Catriona; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Mannermaa, Arto; Hamann, Ute; Chenevix-Trench, Georgia; Blomqvist, Carl; Aittomäki, Kristiina; Easton, Douglas F; Nevanlinna, Heli

    2014-01-01

    Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

  7. Risk model incorporating donor IL6 and IFNG genotype and gastrointestinal GVHD can discriminate patients at high risk of steroid refractory acute GVHD.

    Science.gov (United States)

    Alam, N; Xu, W; Atenafu, E G; Uhm, J; Seftel, M; Gupta, V; Kuruvilla, J; Lipton, J H; Messner, H A; Kim, D D H

    2015-05-01

    Steroid refractory acute GVHD (SR aGVHD) is associated with high morbidity and mortality. This study attempted to generate a risk model for SR aGVHD using 259 single nucleotide polymorphisms (SNPs) in 53 genes of recipients and donors. A total of 268 patients with aGVHD who were treated with systemic steroids were included. Patients were randomly divided into training (n=180) and validation sets (n=88). Clinical risk factors were also evaluated. In the training set, 85 (47.2%) developed SR aGVHD. Gastrointestinal involvement (Prs1800797; P=6.2 × 10(-4)) and IFNG (rs2069727; P=4.4 × 10(-4)) were significant risk factors. Scores were assigned to the above risk factors. Patients were divided into low (score 0, n=74) vs high risk (scores 1-3; n=106) in risk model. Higher incidence of SR aGVHD was noted in the high risk (61.3%) vs the low-risk group (27%; Prs1800797) and IFNG (rs2069727) along with gastrointestinal involvement of aGVHD.

  8. Events per variable for risk differences and relative risks using pseudo-observations

    DEFF Research Database (Denmark)

    Hansen, Stefan Nygaard; Andersen, Per Kragh; Parner, Erik Thorlund

    2014-01-01

    been computed, can be fitted using standard generalized estimating equation software. Regression models can however yield problematic results if the number of covariates is large in relation to the number of events observed. Guidelines of events per variable are often used in practice. These rules...... of thumb for the number of events per variable have primarily been established based on simulation studies for the logistic regression model and Cox regression model. In this paper we conduct a simulation study to examine the small sample behavior of the pseudo-observation method to estimate risk...... differences and relative risks for right-censored data. We investigate how coverage probabilities and relative bias of the pseudo-observation estimator interact with sample size, number of variables and average number of events per variable....

  9. Novel mutations in leukotriene C4 synthase and risk of cardiovascular disease based on genotypes from 50,000 individuals

    DEFF Research Database (Denmark)

    Freiberg, J J; Tybjærg-Hansen, Anne; Nordestgaard, B G

    2010-01-01

    Atherosclerosis is an inflammatory condition where cysteinyl leukotrienes have been identified to play an important role. Furthermore, cysteinyl leukotrienes may also affect thrombus formation. Using prospective, cross-sectional and case-control designs, we tested the hypothesis that hitherto unk...... unknown genetic variation, likely to affect the function of leukotriene C(4) synthase, is associated with risk of venous thromboembolism, ischemic stroke and myocardial infarction....

  10. Genetic Variation in Autophagy-Related Genes Influences the Risk and Phenotype of Buruli Ulcer.

    Directory of Open Access Journals (Sweden)

    Carlos Capela

    2016-04-01

    Full Text Available Buruli ulcer (BU is a severe necrotizing human skin disease caused by Mycobacterium ulcerans. Clinically, presentation is a sum of these diverse pathogenic hits subjected to critical immune-regulatory mechanisms. Among them, autophagy has been demonstrated as a cellular process of critical importance. Since microtubules and dynein are affected by mycolactone, the critical pathogenic exotoxin produced by M. ulcerans, cytoskeleton-related changes might potentially impair the autophagic process and impact the risk and progression of infection.Genetic variants in the autophagy-related genes NOD2, PARK2 and ATG16L1 has been associated with susceptibility to mycobacterial diseases. Here, we investigated their association with BU risk, its severe phenotypes and its progression to an ulcerative form.Genetic variants were genotyped using KASPar chemistry in 208 BU patients (70.2% with an ulcerative form and 28% in severe WHO category 3 phenotype and 300 healthy endemic controls.The rs1333955 SNP in PARK2 was significantly associated with increased susceptibility to BU [odds ratio (OR, 1.43; P = 0.05]. In addition, both the rs9302752 and rs2066842 SNPs in NOD2 gee significantly increased the predisposition of patients to develop category 3 (OR, 2.23; P = 0.02; and OR 12.7; P = 0.03, respectively, whereas the rs2241880 SNP in ATG16L1 was found to significantly protect patients from presenting the ulcer phenotype (OR, 0.35; P = 0.02.Our findings indicate that specific genetic variants in autophagy-related genes influence susceptibility to the development of BU and its progression to severe phenotypes.

  11. Correlations between major risk factors and closely related Mycobacterium tuberculosis isolates grouped by three current enotyping procedures: a population-based study in northeast Mexico

    Directory of Open Access Journals (Sweden)

    Katia Peñuelas-Urquides

    2014-09-01

    Full Text Available The characteristics of tuberculosis (TB patients related to a chain of recent TB transmissions were investigated. Mycobacterium tuberculosis (MTB isolates (120 were genotyped using the restriction fragment length polymorphism-IS6110 (R, spacer oligotyping (S and mycobacterial interspersed repetitive units-variable number of tandem repeats (M methods. The MTB isolates were clustered and the clusters were grouped according to the similarities of their genotypes. Spearman’s rank correlation coefficients between the groups of MTB isolates with similar genotypes and those patient characteristics indicating a risk for a pulmonary TB (PTB chain transmission were ana- lysed. The isolates showing similar genotypes were distributed as follows: SMR (5%, SM (12.5%, SR (1.67%, MR (0%, S (46.67%, M (5% and R (0%. The remaining 35 cases were orphans. SMR exhibited a significant correlation (p < 0.05 with visits to clinics, municipalities and comorbidities (primarily diabetes mellitus. S correlated with drug consumption and M with comorbidities. SMR is needed to identify a social network in metropolitan areas for PTB transmission and S and M are able to detect risk factors as secondary components of a transmission chain of TB.

  12. Correlations between major risk factors and closely related Mycobacterium tuberculosis isolates grouped by three current enotyping procedures: a population-based study in northeast Mexico

    Science.gov (United States)

    Peñuelas-Urquides, Katia; Martínez-Rodríguez, Herminia Guadalupe; Enciso-Moreno, José Antonio; Molina-Salinas, Gloria María; Silva-Ramírez, Beatriz; Padilla-Rivas, Gerardo Raymundo; Vera-Cabrera, Lucio; Torres-de-la-Cruz, Víctor Manuel; Martínez-Martínez, Yazmin Berenice; Ortega-García, Jorge Luis; Garza-Treviño, Elsa Nancy; Enciso-Moreno, Leonor; Saucedo-Cárdenas, Odila; Becerril-Montes, Pola; Said-Fernández/, Salvador

    2014-01-01

    The characteristics of tuberculosis (TB) patients related to a chain of recent TB transmissions were investigated. Mycobacterium tuberculosis (MTB) isolates (120) were genotyped using the restriction fragment length polymorphism-IS6110 (R), spacer oligotyping (S) and mycobacterial interspersed repetitive units-variable number of tandem repeats (M) methods. The MTB isolates were clustered and the clusters were grouped according to the similarities of their genotypes. Spearman’s rank correlation coefficients between the groups of MTB isolates with similar genotypes and those patient characteristics indicating a risk for a pulmonary TB (PTB) chain transmission were ana- lysed. The isolates showing similar genotypes were distributed as follows: SMR (5%), SM (12.5%), SR (1.67%), MR (0%), S (46.67%), M (5%) and R (0%). The remaining 35 cases were orphans. SMR exhibited a significant correlation (p < 0.05) with visits to clinics, municipalities and comorbidities (primarily diabetes mellitus). S correlated with drug consumption and M with comorbidities. SMR is needed to identify a social network in metropolitan areas for PTB transmission and S and M are able to detect risk factors as secondary components of a transmission chain of TB. PMID:25317710

  13. Signaling Pathways Related to Protein Synthesis and Amino Acid Concentration in Pig Skeletal Muscles Depend on the Dietary Protein Level, Genotype and Developmental Stages.

    Directory of Open Access Journals (Sweden)

    Yingying Liu

    Full Text Available Muscle growth is regulated by the homeostatic balance of the biosynthesis and degradation of muscle proteins. To elucidate the molecular interactions among diet, pig genotype, and physiological stage, we examined the effect of dietary protein concentration, pig genotype, and physiological stages on amino acid (AA pools, protein deposition, and related signaling pathways in different types of skeletal muscles. The study used 48 Landrace pigs and 48 pure-bred Bama mini-pigs assigned to each of 2 dietary treatments: lower/GB (Chinese conventional diet- or higher/NRC (National Research Council-protein diet. Diets were fed from 5 weeks of age to respective market weights of each genotype. Samples of biceps femoris muscle (BFM, type I and longissimus dorsi muscle (LDM, type II were collected at nursery, growing, and finishing phases according to the physiological stage of each genotype, to determine the AA concentrations, mRNA levels for growth-related genes in muscles, and protein abundances of mechanistic target of rapamycin (mTOR signaling pathway. Our data showed that the concentrations of most AAs in LDM and BFM of pigs increased (P<0.05 gradually with increasing age. Bama mini-pigs had generally higher (P<0.05 muscle concentrations of flavor-related AA, including Met, Phe, Tyr, Pro, and Ser, compared with Landrace pigs. The mRNA levels for myogenic determining factor, myogenin, myocyte-specific enhancer binding factor 2 A, and myostatin of Bama mini-pigs were higher (P<0.05 than those of Landrace pigs, while total and phosphorylated protein levels for protein kinase B, mTOR, and p70 ribosomal protein S6 kinases (p70S6K, and ratios of p-mTOR/mTOR, p-AKT/AKT, and p-p70S6K/p70S6K were lower (P<0.05. There was a significant pig genotype-dependent effect of dietary protein on the levels for mTOR and p70S6K. When compared with the higher protein-NRC diet, the lower protein-GB diet increased (P<0.05 the levels for mTOR and p70S6K in Bama mini-pigs, but

  14. EPA's Response to Health Risks from Dioxin and Related ...

    Science.gov (United States)

    In 2003, EPA produced an external review draft of a multi-year comprehensive reassessment of dioxin exposure and human health effects. This reassessment, Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds, was submitted to the National Academy of Sciences (NAS) for review in October 2004. In 2006, the NAS expert panel published its review titled Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment. The NAS expert panel’s Key Findings, as listed in the Public Summary of its review, identified “three areas that require substantial improvement to support a scientifically robust health assessment: •Justification of approaches to dose-response modeling for cancer and non-cancer end points. •Transparency and clarity in selection of key data sets for analysis. •Transparency, thoroughness, and clarity in quantitative uncertainty analysis.” The NAS also recommended that “EPA routinely monitor new scientific information related to TCDD…with the understanding that future revisions should provide a risk assessment based on the current state-of-the-science.” The objective of this project is to respond to NAS coments on dose-response modeling conducted in the EPA Reassessment of the health effects associated with dioxin exposure. In order to do this, we will address the Key Findings of the NAS review in a transparent and open manner.

  15. Reward, attention, and HIV-related risk in HIV+ individuals.

    Science.gov (United States)

    Anderson, Brian A; Kronemer, Sharif I; Rilee, Jessica J; Sacktor, Ned; Marvel, Cherie L

    2016-08-01

    Human immunodeficiency virus (HIV) is often contracted through engaging in risky reward-motivated behaviors such as needle sharing and unprotected sex. Understanding the factors that make an individual more vulnerable to succumbing to the temptation to engage in these risky behaviors is important to limiting the spread of HIV. One potential source of this vulnerability concerns the degree to which an individual is able to resist paying attention to irrelevant reward information. In the present study, we examine this possible link by characterizing individual differences in value-based attentional bias in a sample of HIV+ individuals with varying histories of risk-taking behavior. Participants learned associations between experimental stimuli and monetary reward outcome. The degree of attentional bias for these reward-associated stimuli, reflected in their ability to capture attention when presented as task-irrelevant distractors, was then assessed both immediately and six months following reward learning. Value-driven attentional capture was related to substance abuse history and non-planning impulsiveness during the time leading up to contraction of HIV as measured via self-report. These findings suggest a link between the ability to ignore reward-associated information and prior HIV-related risk-taking behavior. Additionally, particular aspects of HIV-associated neurocognitive disorders were related to attentional bias, including motor deficits commonly associated with HIV-induced damage to the basal ganglia. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Primary Screening for Cervical Cancer Based on High-Risk Human Papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping, in Comparison to Cytology

    Science.gov (United States)

    Constantinidis, Theocharis; Constantinidis, Theodoros C.

    2015-01-01

    Objectives The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. Methods The study, conducted by the “HEllenic Real life Multicentric cErvical Screening” (HERMES) study group, involved the recruitment of 4,009 women, aged 25–55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Results Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25–29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). Conclusion HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18

  17. UGT1A1 (TA)n genotype is not the major risk factor of cholelithiasis in sickle cell disease children.

    Science.gov (United States)

    Joly, Philippe; Renoux, Céline; Lacan, Philippe; Bertrand, Yves; Cannas, Giovanna; Garnier, Nathalie; Cuzzubbo, Daniella; Kebaïli, Kamila; Renard, Cécile; Gauthier, Alexandra; Pialoux, Vincent; Martin, Cyril; Romana, Marc; Connes, Philippe

    2017-03-01

    Because of the increased hemolytic rate, a significant proportion of patients with sickle cell disease (SCD) are prone to develop cholelithiasis. The present study investigated the role of several genetic factors (UGT1A1 promoter (TA)n repeat polymorphism, alpha-globin status), hematological parameters, clinical severity, and hydroxyurea (HU) therapy on the occurrence of cholelithiasis in SCD. One hundred and fifty-eight children (2-18 yr old) regularly followed at the University Hospital of Lyon (France) were included. A multivariate Cox model was used to test the associations between cholelithiasis and the different parameters analyzed. We confirmed that alpha-thalassemia and low basal reticulocyte (RET) count were independent protective factors for cholelithiasis while 7/7, 8/8 and 7/8 UGT1A1 (TA)n genotypes were independent predisposing factors for this complication. We also showed for the first time that HU treatment decreased the risk for cholelithiasis while frequent vaso-occlusive crises and acute chest syndrome events increased that risk. Our findings demonstrate that UGT1A1 (TA)n polymorphism is not the only factor triggering gallstone formation in SCD. Cholelithiasis is also modulated by RET count, the number of deleted alpha-genes, HU therapy and the frequency of vaso-occlusive events. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Risk of Misinforming and Message Customization in Customer Related Management

    Directory of Open Access Journals (Sweden)

    Dimitar Grozdanov Christozov

    2015-08-01

    Full Text Available This paper discusses applications of the measures of the risk of misinforming and the role of the warranty of misinforming in the context of the informing component of Customer Related Management (CRM issues. This study consists of two parts. Firstly, we propose an approach for customers’ grouping based on their attitude toward assessing product's properties and their expertise on the terminology/domain of the seller’s message describing the product. Also we discuss what the most appropriate personal/group warranty is for each of these group/clusters.

  19. Simulating the market coefficient of relative risk aversion

    Directory of Open Access Journals (Sweden)

    Samih Antoine Azar

    2014-12-01

    Full Text Available In this paper, expected utility, defined by a Taylor series expansion around expected wealth, is maximized. The coefficient of relative risk aversion (CRRA that is commensurate with a 100% investment in the risky asset is simulated. The following parameters are varied: the riskless return, the market standard deviation, the market stock premium, and the skewness and the kurtosis of the risky return. Both the high extremes and the low extremes are considered. With these figures, the upper bound of the market CRRA is 3.021 and the lower bound is 0.466. Log utility, which corresponds to a CRRA of 1, is not excluded.

  20. Update on procedure-related risks for prenatal diagnosis techniques

    DEFF Research Database (Denmark)

    Tabor, Ann; Alfirevic, Zarko

    2010-01-01

    from randomised controlled trials as well as from systematic reviews and a large national registry study are consistent with a procedure-related miscarriage rate of 0.5-1.0% for amniocentesis as well as for chorionic villus sampling (CVS). In single-center studies performance may be remarkably good due...... to very skilled operators, but these figures cannot be used for general counselling. Amniocentesis performed prior to 15 weeks had a significantly higher miscarriage rate than CVS and mid-trimester amniocentesis, and also increased the risk of talipes equinovarus. Amniocentesis should therefore...

  1. Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes

    Directory of Open Access Journals (Sweden)

    Rutter Joni L

    2004-03-01

    Full Text Available Abstract Background Subtle functional deficiencies in highly conserved DNA repair or growth regulatory processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. Polymorphisms in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk. Thus, 19 single nucleotide polymorphisms (SNPs in eight genes involved in base excision repair (XRCC1, APEX, POLD1, BRCA1 protein interaction (BRIP1, ZNF350, BRCA2, and growth regulation (TGFß1, IGFBP3 were evaluated. Methods Genomic DNA samples were used in Taqman 5'-nuclease assays for most SNPs. Breast cancer risk to ages 50 and 70 were estimated using the kin-cohort method in which genotypes of relatives are inferred based on the known genotype of the index subject and Mendelian inheritance patterns. Family cancer history data was collected from a series of genotyped breast cancer cases (N = 748 identified within a cohort of female US radiologic technologists. Among 2,430 female first-degree relatives of cases, 190 breast cancers were reported. Results Genotypes associated with increased risk were: XRCC1 R194W (WW and RW vs. RR, cumulative risk up to age 70, risk ratio (RR = 2.3; 95% CI 1.3–3.8; XRCC1 R399Q (QQ vs. RR, cumulative risk up to age 70, RR = 1.9; 1.1–3.9; and BRIP1 (or BACH1 P919S (SS vs. PP, cumulative risk up to age 50, RR = 6.9; 1.6–29.3. The risk for those heterozygous for BRCA2 N372H and APEX D148E were significantly lower than risks for homozygotes of either allele, and these were the only two results that remained significant after adjusting for multiple comparisons. No associations with breast cancer were observed for: APEX Q51H; XRCC1 R280H; IGFPB3 -202A>C; TGFß1 L10P, P25R, and T263I; BRCA2 N289H and T1915M; BRIP1 -64A>C; and ZNF350 (or ZBRK1 1845C>T, L66P, R501S, and S472P. Conclusion Some variants in genes within the base-excision repair pathway (XRCC1 and

  2. Transfusion-related acute lung injury risk mitigation: an update.

    Science.gov (United States)

    Otrock, Z K; Liu, C; Grossman, B J

    2017-09-25

    Transfusion-related acute lung injury (TRALI) is a life-threatening complication of transfusion. Greater understanding of the pathophysiology of this syndrome has much improved during the last two decades. Plasma-containing components from female donors with leucocyte antibodies were responsible for the majority of TRALI fatalities before mitigation strategies were implemented. Over the past 15 years, measures to mitigate risk for TRALI have been implemented worldwide and they continued to evolve with time. The AABB requires that all plasma containing components and whole blood for transfusion must be collected from men, women who have not been pregnant, or women who have tested negative for human leucocyte antigen antibodies. Although the incidence of TRALI has decreased following the institution of TRALI mitigation strategies, TRALI is still the most common cause of transfusion-associated death in the United States. In this review, we focus on TRALI risk mitigation strategies. We describe the measures taken by blood collection facilities to reduce the risk of TRALI in the United States, Canada and European countries. We also review the literature for the effectiveness of these measures. © 2017 International Society of Blood Transfusion.

  3. Substance-related traffic-risk behaviors among college students

    Science.gov (United States)

    Arria, Amelia M.; Caldeira, Kimberly M.; Vincent, Kathryn B.; Garnier-Dykstra, Laura M.; O’Grady, Kevin E.

    2011-01-01

    Aims Drunk driving is a major public health concern, but drugged driving has received little attention. This study examines drugged driving and riding with a drugged driver in a college student sample, in terms of prevalence, age-related trends, race/sex differences, overlap with drunk driving, and risk for alcohol and marijuana dependence. Methods Students (N=1194) ages 19 to 22 were interviewed annually for three years about past-year frequency of drugged driving, riding with a drugged/drunk driver, drunk driving, access to a car, and alcohol/drug dependence. Annual follow-up rates were excellent (88% to 91%). Repeated measures analyses were conducted using generalized estimating equations (GEE). Results One in six (17%wt) 19-year-olds with access to a car drove drugged in the past year; prevalence remained stable through age 22. Drugged driving was more prevalent among males (pdrunk (ranges between 47% and 60%). Both drugged and drunk driving were independently associated with increased risk for alcohol dependence, holding constant age, sex, and race. Drunk driving did not add to the risk for marijuana dependence in the context of drugged driving. Conclusions The prevalence of drugged driving is similar to drunk driving among college students. Both are strongly associated with underlying alcohol and drug dependence. Prevention and treatment implications are discussed. PMID:21601379

  4. Abrasive blasting agents: designing studies to evaluate relative risk.

    Science.gov (United States)

    Hubbs, Ann; Greskevitch, Mark; Kuempel, Eileen; Suarez, Fernando; Toraason, Mark

    Workers exposed to respirable crystalline silica used in abrasive blasting are at increased risk of developing a debilitating and often fatal fibrotic lung disease called silicosis. The National Institute for Occupational Safety and Health (NIOSH) recommends that silica sand be prohibited as abrasive blasting material and that less hazardous materials be used in blasting operations. However, data are needed on the relative risks associated with exposure to abrasive blasting materials other than silica. NIOSH has completed acute studies in rats (Hubbs et al., 2001; Porter et al., 2002). To provide dose-response data applicable to making recommendation for occupational exposure limits, NIOSH has collaborated with the National Toxicology Program (NTP) to design longer term studies with silica substitutes. For risk assessment purposes, selected doses will include concentrations that are relevant to human exposures. Rat lung burdens achieved should be comparable to those estimated in humans with working lifetime exposures, even if this results in "overloading" doses in rats. To quantify both dose and response, retained particle burdens in the lungs and lung-associated lymph nodes will be measured, as well as biochemical and pathological indices of pulmonary response. This design will facilitate assessment of the pulmonary fibrogenic potential of inhaled abrasive blasting agents at occupationally relevant concentrations.

  5. Does greater adiposity increase blood pressure and hypertension risk?: Mendelian randomization using the FTO/MC4R genotype

    DEFF Research Database (Denmark)

    Timpson, Nicholas J; Harbord, Roger; Davey Smith, George;

    2009-01-01

    Elevated blood pressure increases the risk of experiencing cardiovascular events like myocardial infarction and stroke. Current observational data suggest that body mass index may have a causal role in the etiology of hypertension, but this may be influenced by confounding and reverse causation...... between body mass index and blood pressure. In analyses including those taking antihypertensive drugs, but for whom appropriate adjustment had been made, systolic blood pressure was seen to increase by 3.85 mm Hg (95% CI: 1.88 to 5.83 mm Hg) for each 10% increase in body mass index (P=0...

  6. Autoantibodies to IA-2beta improve diabetes risk assessment in high-risk relatives

    DEFF Research Database (Denmark)

    Achenbach, P; Bonifacio, E; Williams, A J K;

    2008-01-01

    . METHODS: Autoantibodies to insulin (IAA), glutamate decarboxylase (GADA) and IA-2 (IA2A) were measured in 549 participants at study entry, and IA2A-positive samples tested for IA2betaA. First-phase insulin response (FPIR) and oral glucose tolerance were determined at baseline. RESULTS: Of 212 ICA/IA2A......-positive participants (median age 12.1 years; 57% male), 113 developed diabetes (5 year cumulative risk 56%), and 148 were also GADA-positive and IAA-positive (4Ab-positive). IA2betaA were detected in 137 (65%) ICA/IA2A-positive participants and were associated with an increased 5 year diabetes risk (IA2beta......A-positive 65 vs 39% in IA2betaA-negative, p=0.0002). The effect was most marked in 4Ab-positive relatives (72% vs 52%, p=0.003). Metabolic testing further refined risk assessment. Among 101 4Ab-positive relatives with IA2betaA, the 5 year risk was 94% in those with a low FPIR (vs 50% in those with a normal...

  7. A “Forward Genomics” Approach Links Genotype to Phenotype using Independent Phenotypic Losses among Related Species

    Directory of Open Access Journals (Sweden)

    Michael Hiller

    2012-10-01

    Full Text Available Genotype-phenotype mapping is hampered by countless genomic changes between species. We introduce a computational “forward genomics” strategy that—given only an independently lost phenotype and whole genomes—matches genomic and phenotypic loss patterns to associate specific genomic regions with this phenotype. We conducted genome-wide screens for two metabolic phenotypes. First, our approach correctly matches the inactivated Gulo gene exactly with the species that lost the ability to synthesize vitamin C. Second, we attribute naturally low biliary phospholipid levels in guinea pigs and horses to the inactivated phospholipid transporter Abcb4. Human ABCB4 mutations also result in low phospholipid levels but lead to severe liver disease, suggesting compensatory mechanisms in guinea pig and horse. Our simulation studies, counts of independent changes in existing phenotype surveys, and the forthcoming availability of many new genomes all suggest that forward genomics can be applied to many phenotypes, including those relevant for human evolution and disease.

  8. Molecular Cloning, Expression Pattern and Genotypic Effects on Glucoraphanin Biosynthetic Related Genes in Chinese Kale (Brassica oleracea var. alboglabra Bailey).

    Science.gov (United States)

    Yin, Ling; Chen, Changming; Chen, Guoju; Cao, Bihao; Lei, Jianjun

    2015-11-11

    Glucoraphanin is a plant secondary metabolite that is involved in plant defense and imparts health-promoting properties to cruciferous vegetables. In this study, three genes involved in glucoraphanin metabolism, branched-chain aminotransferase 4 (BCAT4), methylthioalkylmalate synthase 1 (MAM1) and dihomomethionine N-hydroxylase (CYP79F1), were cloned from Chinese kale (Brassica oleracea var. alboglabra Bailey). Sequence homology and phylogenetic analysis identified these genes and confirmed the evolutionary status of Chinese kale. The transcript levels of BCAT4, MAM1 and CYP79F1 were higher in cotyledon, leaf and stem compared with flower and silique. BCAT4, MAM1 and CYP79F1 were expressed throughout leaf development with lower transcript levels during the younger stages. Glucoraphanin content varied extensively among different varieties, which ranged from 0.25 to 2.73 µmol·g(-1) DW (dry weight). Expression levels of BCAT4 and MAM1 were high at vegetative-reproductive transition phase, while CYP79F1 was expressed high at reproductive phase. BCAT4, MAM1 and CYP79F1 were expressed significantly high in genotypes with high glucoraphanin content. All the results provided a better understanding of the roles of BCAT4, MAM1 and CYP79F1 in the glucoraphanin biosynthesis of Chinese kale.

  9. Integration and relative value of biomarkers for prediction of MCI to AD progression: Spatial patterns of brain atrophy, cognitive scores, APOE genotype and CSF biomarkers

    Directory of Open Access Journals (Sweden)

    Xiao Da

    2014-01-01

    Full Text Available This study evaluates the individual, as well as relative and joint value of indices obtained from magnetic resonance imaging (MRI patterns of brain atrophy (quantified by the SPARE-AD index, cerebrospinal fluid (CSF biomarkers, APOE genotype, and cognitive performance (ADAS-Cog in progression from mild cognitive impairment (MCI to Alzheimer's disease (AD within a variable follow-up period up to 6 years, using data from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1. SPARE-AD was first established as a highly sensitive and specific MRI-marker of AD vs. cognitively normal (CN subjects (AUC = 0.98. Baseline predictive values of all aforementioned indices were then compared using survival analysis on 381 MCI subjects. SPARE-AD and ADAS-Cog were found to have similar predictive value, and their combination was significantly better than their individual performance. APOE genotype did not significantly improve prediction, although the combination of SPARE-AD, ADAS-Cog and APOE ε4 provided the highest hazard ratio estimates of 17.8 (last vs. first quartile. In a subset of 192 MCI patients who also had CSF biomarkers, the addition of Aβ1–42, t-tau, and p-tau181p to the previous model did not improve predictive value significantly over SPARE-AD and ADAS-Cog combined. Importantly, in amyloid-negative patients with MCI, SPARE-AD had high predictive power of clinical progression. Our findings suggest that SPARE-AD and ADAS-Cog in combination offer the highest predictive power of conversion from MCI to AD, which is improved, albeit not significantly, by APOE genotype. The finding that SPARE-AD in amyloid-negative MCI patients was predictive of clinical progression is not expected under the amyloid hypothesis and merits further investigation.

  10. An SNP-based saturated genetic map and QTL analysis of fruit-related traits in Zucchini using Genotyping-by-sequencing.

    Science.gov (United States)

    Montero-Pau, Javier; Blanca, José; Esteras, Cristina; Martínez-Pérez, Eva Ma; Gómez, Pedro; Monforte, Antonio J; Cañizares, Joaquín; Picó, Belén

    2017-01-18

    Cucurbita pepo is a cucurbit with growing economic importance worldwide. Zucchini morphotype is the most important within this highly variable species. Recently, transcriptome and Simple Sequence Repeat (SSR)- and Single Nucleotide Polymorphism (SNP)-based medium density maps have been reported, however further genomic tools are needed for efficient molecular breeding in the species. Our objective is to combine currently available complete transcriptomes and the Zucchini genome sequence with high throughput genotyping methods, mapping population development and extensive phenotyping to facilitate the advance of genomic research in this species. We report the Genotyping-by-sequencing analysis of a RIL population developed from the inter subspecific cross Zucchini x Scallop (ssp. pepo x ssp. ovifera). Several thousands of SNP markers were identified and genotyped, followed by the construction of a high-density linkage map based on 7,718 SNPs (average of 386 markers/linkage group) covering 2,817.6 cM of the whole genome, which is a great improvement with respect to previous maps. A QTL analysis was performed using phenotypic data obtained from the RIL population from three environments. In total, 48 consistent QTLs for vine, flowering and fruit quality traits were detected on the basis of a multiple-environment analysis, distributed in 33 independent positions in 15 LGs, and each QTL explained 1.5-62.9% of the phenotypic variance. Eight major QTLs, which could explain greater than 20% of the phenotypic variation were detected and the underlying candidate genes identified. Here we report the first SNP saturated map in the species, anchored to the physical map. Additionally, several consistent QTLs related to early flowering, fruit shape and length, and rind and flesh color are reported as well as candidate genes for them. This information will enhance molecular breeding in C. pepo and will assist the gene cloning underlying the studied QTLs, helping to reveal the

  11. Integration and relative value of biomarkers for prediction of MCI to AD progression: spatial patterns of brain atrophy, cognitive scores, APOE genotype and CSF biomarkers.

    Science.gov (United States)

    Da, Xiao; Toledo, Jon B; Zee, Jarcy; Wolk, David A; Xie, Sharon X; Ou, Yangming; Shacklett, Amanda; Parmpi, Paraskevi; Shaw, Leslie; Trojanowski, John Q; Davatzikos, Christos

    2014-01-01

    This study evaluates the individual, as well as relative and joint value of indices obtained from magnetic resonance imaging (MRI) patterns of brain atrophy (quantified by the SPARE-AD index), cerebrospinal fluid (CSF) biomarkers, APOE genotype, and cognitive performance (ADAS-Cog) in progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) within a variable follow-up period up to 6 years, using data from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1). SPARE-AD was first established as a highly sensitive and specific MRI-marker of AD vs. cognitively normal (CN) subjects (AUC = 0.98). Baseline predictive values of all aforementioned indices were then compared using survival analysis on 381 MCI subjects. SPARE-AD and ADAS-Cog were found to have similar predictive value, and their combination was significantly better than their individual performance. APOE genotype did not significantly improve prediction, although the combination of SPARE-AD, ADAS-Cog and APOE ε4 provided the highest hazard ratio estimates of 17.8 (last vs. first quartile). In a subset of 192 MCI patients who also had CSF biomarkers, the addition of Aβ1-42, t-tau, and p-tau181p to the previous model did not improve predictive value significantly over SPARE-AD and ADAS-Cog combined. Importantly, in amyloid-negative patients with MCI, SPARE-AD had high predictive power of clinical progression. Our findings suggest that SPARE-AD and ADAS-Cog in combination offer the highest predictive power of conversion from MCI to AD, which is improved, albeit not significantly, by APOE genotype. The finding that SPARE-AD in amyloid-negative MCI patients was predictive of clinical progression is not expected under the amyloid hypothesis and merits further investigation.

  12. Energy drinks and alcohol-related risk among young adults.

    Science.gov (United States)

    Caviness, Celeste M; Anderson, Bradley J; Stein, Michael D

    2017-06-16

    Energy drink consumption, with or without concurrent alcohol use, is common among young adults. This study sought to clarify risk for negative alcohol outcomes related to the timing of energy drink use. The authors interviewed a community sample of 481 young adults, aged 18-25, who drank alcohol in the last month. Past-30-day energy drink use was operationalized as no-use, use without concurrent alcohol, and concurrent use of energy drinks with alcohol ("within a couple of hours"). Negative alcohol outcomes included past-30-day binge drinking, past-30-day alcohol use disorder, and drinking-related consequences. Just over half (50.5%) reported no use of energy drinks,18.3% reported using energy drinks without concurrent alcohol use, and 31.2% reported concurrent use of energy drinks and alcohol. Relative to those who reported concurrent use of energy drinks with alcohol, and controlling for background characteristics and frequency of alcohol consumption, those who didn't use energy drinks and those who used without concurrent alcohol use had significantly lower binge drinking, negative consequences, and rates of alcohol use disorder (P energy drink without concurrent alcohol groups on any alcohol-related measure (P > .10 for all outcomes). Concurrent energy drink and alcohol use is associated with increased risk for negative alcohol consequences in young adults. Clinicians providing care to young adults could consider asking patients about concurrent energy drink and alcohol use as a way to begin a conversation about risky alcohol consumption while addressing 2 substances commonly used by this population.

  13. Relative risk for concussions in young female soccer players.

    Science.gov (United States)

    Strand, Sarah; Lechuga, David; Zachariah, Thomas; Beaulieu, Kathryn

    2015-01-01

    The objective of this study was to determine the relative risk and reported symptoms of concussions in 11- to 13-year-old, female soccer players. For this, a survey to compare the reported incidence of concussion in age-matched female soccer players to nonsoccer players was performed. The survey included 342 girls between the ages of 11 and 13: 195 were involved in an organized soccer team and 147 were not involved in organized soccer but were allowed to participate in any other sport or activity. A total of 94 of the 195 soccer players, or 48%, reported at least one symptom consistent with a concussion. The most prevalent symptom for these girls was headache (84%). A total of 34 of the 147 nonsoccer players, or 23%, reported at least one symptom consistent with a concussion in the previous six months. These results determined that the relative risk of probable concussions among 11- to 13-year-old, female soccer players is 2.09 (p concussions in young female soccer players is significantly higher than in a control group of nonsoccer players of the same sex and age.

  14. Association between risk factors, basal viral load, virus genotype and the degree of liver fibrosis with the response to the therapy in patients with chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Vuković Vuk R.

    2015-01-01

    Full Text Available Background/Aim. Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic disease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with response to the therapy in patients with chronic hepatitis C virus (HCV infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV genotype were analyzed. Methods. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for genotype 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. Results. In the group of non-responding patients genotype 1 was represented with 100%, while in the other groups, although predominantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive substances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse responders and non-responders. Conclusion. The results of our study showed that the treatment outcome of chronic HCV infection was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver. [Projekat Ministarstva nauke Republike Srbije, br. III41010

  15. APOL1 risk variants predict histopathology and progression to ESRD in HIV-related kidney disease.

    Science.gov (United States)

    Fine, Derek M; Wasser, Walter G; Estrella, Michelle M; Atta, Mohamed G; Kuperman, Michael; Shemer, Revital; Rajasekaran, Arun; Tzur, Shay; Racusen, Lorraine C; Skorecki, Karl

    2012-02-01

    With earlier institution of antiretroviral therapy, kidney diseases other than HIV-associated nephropathy (HIVAN) predominate in HIV-infected persons. Outcomes for these diseases are typically worse among those infected with HIV, but the reasons for this are not clear. Here, we examined the role of APOL1 risk variants in predicting renal histopathology and progression to ESRD in 98 HIV-infected African Americans with non-HIVAN kidney disease on biopsy. We used survival analysis to determine time to ESRD associated with APOL1 genotype. Among the 29 patients with two APOL1 risk alleles, the majority (76%) had FSGS and 10% had hypertensive nephrosclerosis. In contrast, among the 54 patients with one APOL1 risk allele, 47% had immune-complex GN as the predominant lesion and only 23% had FSGS. Among the 25 patients with no APOL1 risk allele, 40% had immune-complex GN and 12% had FSGS. In 310 person-years of observation, 29 patients progressed to ESRD. In adjusted analyses, individuals with two APOL1 risk alleles had a nearly three-fold higher risk for ESRD compared with those with one or zero risk alleles (P=0.03). In summary, these data demonstrate an association between APOL1 variants and renal outcomes in non-HIVAN kidney disease, suggesting a possible use for APOL1 genotyping to help guide the care of HIV-infected patients.

  16. Risk Management in Supply Chain using Consistent Fuzzy Preference Relations

    OpenAIRE

    Ahmad Jafarnejad; Mehran Ebrahimi; Mohammad Ali Abbaszadeh; Seyed Mehdi Abtahi

    2014-01-01

    Nowadays, supply chains are exposed to numerous risks. Thus, to success in risky business environment, it is imperative for firms to systematically manage supply chain risks. Risk management is the identification, assessment, and prioritization of supply chain risks. The purpose of this paper is to propose a comprehensive approach to risk management in supply chains. Thus, by an appropriate review of the literature, supply chain risk sources are identified in six areas. Then, a CFPR method is...

  17. Association of ADH4 genetic variants with alcohol dependence risk and related phenotypes: results from a larger multicenter association study.

    Science.gov (United States)

    Preuss, Ulrich W; Ridinger, Monika; Rujescu, Dan; Samochowiec, Jerzy; Fehr, Christoph; Wurst, Friedrich M; Koller, Gabriele; Bondy, Brigitta; Wodarz, Norbert; Debniak, Tadeusz; Grzywacz, Anna; Soyka, Michael; Zill, Peter

    2011-04-01

    Genetic variants of the alcohol-metabolizing enzyme ADH4, located on chromosome 4q22-4q23, have been related to alcohol dependence (AD) risk in previous research. The aim of this association study in a large multicenter sample of alcohol-dependent individuals and controls is to confirm ADH4 single nucleotide polymorphism (SNP) and haplotype association with AD and relevant related phenotypes. One thousand, six hundred and twenty-two (1622) inpatient subjects and 1469 control subjects with DSM-IV. AD from four addiction treatment centres were included. Characteristics of AD and related phenotypes including alcohol withdrawal, Cloninger's type I and II and first ages of drinking, regular drinking and AD onset were obtained using standardized structured interviews. After subjects were genotyped for 2 ADH4 polymorphisms, single SNP case-control and haplotype analyses were conducted. Both variants--rs1800759 and rs1042364--and the A-A and C-G haplotypes were significantly related to AD across samples. Furthermore, associations with AD-related phenotypes and subtypes revealed a potential protective influence of this haplotype. This study confirms the significant relationship of ADH4 variants with AD and related phenotypes. While the rs1800759 and rs1042364 A-A haplotype had a potential protective influence on the risk for several AD-related phenotypes, this effect is rather small compared to functional variants of other alcohol or acetaldehyde-metabolizing enzymes like ALDH2*2 or ADH1B*2.

  18. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: Systematic review and meta-analysis of 14 015 stroke cases and pooled analysis of primary biomarker data from up to 60 883 individuals

    Science.gov (United States)

    Khan, Tauseef A; Shah, Tina; Prieto, David; Zhang, Weili; Price, Jackie; Fowkes, Gerald R; Cooper, Jackie; Talmud, Philippa J; Humphries, Steve E; Sundstrom, Johan; Hubacek, Jaroslav A; Ebrahim, Shah; Lawlor, Debbie A; Ben-Shlomo, Yoav; Abdollahi, Mohammad R; Slooter, Arjen JC; Szolnoki, Zoltan; Sandhu, Manjinder; Wareham, Nicholas; Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne; Fillenbaum, Gerda; Heijmans, Bastiaan T; Katsuya, Tomohiro; Gromadzka, Grazyna; Singleton, Andrew; Ferrucci, Luigi; Hardy, John; Worrall, Bradford; Rich, Stephen S; Matarin, Mar; Whittaker, John; Gaunt, Tom R; Whincup, Peter; Morris, Richard; Deanfield, John; Donald, Ann; Davey Smith, George; Kivimaki, Mika; Kumari, Meena; Smeeth, Liam; Khaw, Kay-Tee; Nalls, Michael; Meschia, James; Sun, Kai; Hui, Rutai; Day, Ian; Hingorani, Aroon D; Casas, Juan P

    2013-01-01

    Background At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk. Methods We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61 730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60 883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT). Results The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84–1.43) for ε2/ε2; 0.85 (95% CrI: 0.78–0.92) for ε2/ε3; 1.05 (95% CrI: 0.89–1.24) for ε2/ε4; 1.05 (95% CrI: 0.99–1.12) for ε3/ε4; and 1.12 (95% CrI: 0.94–1.33) for ε4/ε4 using the ε3/ε3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 × 10−152), apolipoprotein B (P-trend: 8.7 × 10−06) and C-IMT (P-trend: 0.001), and negatively and

  19. Cytochrome P450 1B1 and 2C9 genotypes and risk of ischemic vascular disease, cancer, and chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Bojesen, Stig E; Nordestgaard, Børge G

    2012-01-01

    The aim of this review is to summarize present knowledge of genetic variation in cytochrome P450 1B1 (CYP1B1) and 2C9 (CYP2C9) genes and risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease. The CYP1B1 and CYP2C9 enzymes metabolize...... between genetic variation in CYP1B1 and CYP2C9 and risk of disease with considerable statistical power rebutted the hypotheses that these genetic variants affect risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease....... of female cancer or ischemic vascular disease. Genetic variation in genes coding for CYP1B1 and CYP2C9 enzymes have shown altered enzyme activity affecting levels of metabolites and thus potentially risk of disease. So far, however, findings have been inconsistent. Recently, large studies on the association...

  20. Integrated genotypic analysis of hedgehog-related genes identifies subgroups of keratocystic odontogenic tumor with distinct clinicopathological features.

    Directory of Open Access Journals (Sweden)

    Yasuyuki Shimada

    Full Text Available Keratocystic odontogenic tumor (KCOT arises as part of Gorlin syndrome (GS or as a sporadic lesion. Gene mutations and loss of heterozygosity (LOH of the hedgehog receptor PTCH1 plays an essential role in the pathogenesis of KCOT. However, some KCOT cases lack evidence for gene alteration of PTCH1, suggesting that other genes in the hedgehog pathway may be affected. PTCH2 and SUFU participate in the occurrence of GS-associated tumors, but their roles in KCOT development are unknown. To elucidate the roles of these genes, we enrolled 36 KCOT patients in a study to sequence their entire coding regions of PTCH1, PTCH2 and SUFU. LOH and immunohistochemical expression of these genes, as well as the downstream targets of hedgehog signaling, were examined using surgically-excised KCOT tissues. PTCH1 mutations, including four novel ones, were found in 9 hereditary KCOT patients, but not in sporadic KCOT patients. A pathogenic mutation of PTCH2 or SUFU was not found in any patients. LOH at PTCH1 and SUFU loci correlated with the presence of epithelial budding. KCOT harboring a germline mutation (Type 1 showed nuclear localization of GLI2 and frequent histological findings such as budding and epithelial islands, as well as the highest recurrence rate. KCOT with LOH but without a germline mutation (Type 2 less frequently showed these histological features, and the recurrence rate was lower. KCOT with neither germline mutation nor LOH (Type 3 consisted of two subgroups, Type 3A and 3B, which were characterized by nuclear and cytoplasmic GLI2 localization, respectively. Type 3B rarely exhibited budding and recurrence, behaving as the most amicable entity. The expression patterns of CCND1 and BCL2 tended to correlate with these subgroups. Our data indicates a significant role of PTCH1 and SUFU in the pathogenesis of KCOT, and the genotype-oriented subgroups constitute entities with different potential aggressiveness.

  1. Integrated genotypic analysis of hedgehog-related genes identifies subgroups of keratocystic odontogenic tumor with distinct clinicopathological features.

    Science.gov (United States)

    Shimada, Yasuyuki; Katsube, Ken-ichi; Kabasawa, Yuji; Morita, Kei-ichi; Omura, Ken; Yamaguchi, Akira; Sakamoto, Kei

    2013-01-01

    Keratocystic odontogenic tumor (KCOT) arises as part of Gorlin syndrome (GS) or as a sporadic lesion. Gene mutations and loss of heterozygosity (LOH) of the hedgehog receptor PTCH1 plays an essential role in the pathogenesis of KCOT. However, some KCOT cases lack evidence for gene alteration of PTCH1, suggesting that other genes in the hedgehog pathway may be affected. PTCH2 and SUFU participate in the occurrence of GS-associated tumors, but their roles in KCOT development are unknown. To elucidate the roles of these genes, we enrolled 36 KCOT patients in a study to sequence their entire coding regions of PTCH1, PTCH2 and SUFU. LOH and immunohistochemical expression of these genes, as well as the downstream targets of hedgehog signaling, were examined using surgically-excised KCOT tissues. PTCH1 mutations, including four novel ones, were found in 9 hereditary KCOT patients, but not in sporadic KCOT patients. A pathogenic mutation of PTCH2 or SUFU was not found in any patients. LOH at PTCH1 and SUFU loci correlated with the presence of epithelial budding. KCOT harboring a germline mutation (Type 1) showed nuclear localization of GLI2 and frequent histological findings such as budding and epithelial islands, as well as the highest recurrence rate. KCOT with LOH but without a germline mutation (Type 2) less frequently showed these histological features, and the recurrence rate was lower. KCOT with neither germline mutation nor LOH (Type 3) consisted of two subgroups, Type 3A and 3B, which were characterized by nuclear and cytoplasmic GLI2 localization, respectively. Type 3B rarely exhibited budding and recurrence, behaving as the most amicable entity. The expression patterns of CCND1 and BCL2 tended to correlate with these subgroups. Our data indicates a significant role of PTCH1 and SUFU in the pathogenesis of KCOT, and the genotype-oriented subgroups constitute entities with different potential aggressiveness.

  2. Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

    Science.gov (United States)

    Lipnicki, Darren M.; Crawford, John D.; Thalamuthu, Anbupalam; Castro-Costa, Erico; Stephan, Blossom C. M.; Lipton, Richard B.; Katz, Mindy J.; Ritchie, Karen; Scali, Jacqueline; Ancelin, Marie-Laure; Scarmeas, Nikolaos; Yannakoulia, Mary; Dardiotis, Efthimios; Lam, Linda C. W.; Fung, Ada W. T.; Vaccaro, Roberta; Davin, Annalisa; Kim, Ki Woong; Han, Ji Won; Kim, Tae Hui; Cherbuin, Nicolas; Butterworth, Peter; Scazufca, Marcia; Kumagai, Shuzo; Chen, Sanmei; Narazaki, Kenji; Lobo, Antonio; Lopez-Anton, Raúl; Santabárbara, Javier; Sachdev, Perminder S.

    2017-01-01

    .023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. Conclusions Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data. PMID:28323832

  3. DNA detection and genotypic identification of potentially human-pathogenic microsporidia from asymptomatic pet parrots in South Korea as a risk factor for zoonotic emergence.

    Science.gov (United States)

    Lee, So-Young; Lee, Sung-Seok; Lyoo, Young S; Park, Hee-Myung

    2011-12-01

    We detected and identified genotypes of human-pathogenic microsporidia in fecal samples from 51 asymptomatic captive-bred pet parrots in South Korea. Microsporidia were identified in 8 samples (15.7%); 7 parrots tested positive for Encephalitozoon hellem, and 1 parrot tested positive for both E. hellem and Encephalitozoon cuniculi. In genotypic identifications, E. hellem was present in genotypes 1A and 2B and E. cuniculi was present in genotype II. Pet parrots might be a source of human microsporidian infection.

  4. Two novel distinct COL1A2 mutations highlight the complexity of genotype-phenotype correlations in osteogenesis imperfecta and related connective tissue disorders.

    Science.gov (United States)

    Reuter, Miriam S; Schwabe, Georg C; Ehlers, Christian; Marschall, Christoph; Reis, André; Thiel, Christian; Graul