Integrin beta3 Leu33Pro polymorphism and risk of hip fracture: 25 years follow-up of 9233 adults from the general population

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Tofteng, Charlotte L; Bach-Mortensen, Pernille; Bojesen, Stig E

2007-01-01

OBJECTIVE: Integrin alphavbeta3 is essential for mature osteoclast function and therefore important for the development of osteoporosis and osteoporotic fractures. Integrin alphavbeta3 antagonists have antiresorptive effects in bone. We tested the hypothesis that the Leu33Pro polymorphism...... in the integrin beta3-subunit associates with risk of hip fracture. METHODS: We included 9233 men and women selected at random to represent the Danish general population as participants in the Copenhagen City Heart Study. First-ever hip fractures (n=267) were registered during 25 years follow-up. Log...

Ghrelin gene polymorphisms in rheumatoid arthritis.

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Ozgen, Metin; Koca, Suleyman Serdar; Etem, Ebru Onalan; Yuce, Huseyin; Aydin, Suleyman; Isik, Ahmet

2011-07-01

Ghrelin, an endogenous orexigenic peptide, has anti-inflammatory effects, down-regulates pro-inflammatory cytokines, and its altered levels are reported in various inflammatory diseases. The human preproghrelin (ghrelin/obestatin) gene shows several single nucleotide polymorphisms (SNPs) including Arg51Gln, Leu72Met, Gln90Leu, and A-501C. The aim of this study was to investigate the frequency, and clinical significance, of these four SNPs in a small cohort of Turkish patients with rheumatoid arthritis (RA). The study included 103 patients with RA and 103 healthy controls. In the RA group, disease activity and disease-related damage were assessed using the Disease Activity Score-28 (DAS-28), and the modified Larsen scoring (MLS) methods. In all the participants, genomic DNA was isolated and genotyped by polymerase chain reaction and restriction fragment length polymorphism analysis. The frequencies of ghrelin gene SNPs were 82.5 and 79.6% in the RA and control groups, respectively, and there were no significant differences in terms of genotype distributions and allele frequencies for these four SNPs between the groups. However, the A-501C SNP was found to be associated with early disease onset, and Gln90Leu SNP with less frequent rheumatoid factor positivity, in the RA group. A-501C SNP is associated with earlier onset of RA suggesting that genetic variations in the ghrelin gene may have an impact on RA. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Association of ghrelin Leu72Met polymorphism with type 2 diabetes mellitus in Chinese population.

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Liu, Jing; Liu, Jia; Tian, Li-min; Liu, Ju-xiang; Bing, Ya-jun; Zhang, Ji-ping; Wang, Yun-Fang; Zhang, Lu-yan

2012-08-10

Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to implicate the development of the type 2 diabetes mellitus (T2DM). The Leu72Met (+408C>A) polymorphism of the preproghrelin, has been linked to obesity, insulin resistance and diabetes. To investigate the distribution of ghrelin gene Leu72Met polymorphism and its association with the type 2 diabetes mellitus in Chinese population. We conducted a case-control study on 877 patients with T2DM and 864 controls, which were genotyped by the polymerase chain reaction (PCR) technique, denaturing high performance liquid chromatography (DHPLC) and DNA sequence analysis. Laboratory analyses were carried out in the hospital laboratory. No significant difference in the Leu72Met genotype distributions and allele frequency was observed between type 2 diabetes mellitus and controls (both P>0.05). The polymorphism was not associated with T2DM. However, among the T2DM group, the patients carrying Leu72Leu genotype had significantly increased levels of FPG and serum creatinine compared with variant genotypes (Leu72Met and Met72Met) (Ppolymorphism of the preproghrelin gene was not associated with T2DM in Chinese population. However, it may have some roles in the etiology of insulin resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan.

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Yamawaki, Hiroshi; Futagami, Seiji; Shimpuku, Mayumi; Shindo, Tomotaka; Maruki, Yuuta; Nagoya, Hiroyuki; Kodaka, Yasuhiro; Sato, Hitomi; Gudis, Katya; Kawagoe, Tetsuro; Sakamoto, Choitsu

2015-01-01

There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome III classification. We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and self-rating questionnaires for depression (SRQ-D) scores to determine status of depression. The Arg51Gln (346G->A), preproghrelin (3056T->C), Leu72Met (408C->A), Gln90Leu (3412T->A) and G-protein 3 (825C->T) polymorphisms were analyzed in the DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. There was a significant relationship between the Gln90Leu3412 genotype and SRQ-D score in FD patients (P = 0.009). Area under the curve at 15 minutes (AUC15) value was significantly associated with the Leu72Met408 genotype (P = 0.015) but not with entire gastric emptying. The Leu72Met (408C->A) single nucleotide polymorphism was significantly associated with early phase of gastric emptying in FD patients. Further studies will be necessary to clarify the association between ghrelin gene single nucleotide polymorphisms and early phase of gastric emptying in FD patients.

Preproghrelin Leu72Met polymorphism in obese Korean children.

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Jo, Dae-Sun; Kim, Se-Lim; Kim, Sun-Young; Hwang, Pyoung Han; Lee, Kee-Hyoung; Lee, Dae-Yeol

2005-11-01

Ghrelin is a novel gut-brain peptide that has somatotropic, orexigenic, and adipogenic effects. We examined the preproghrelin Leu72Met polymorphism in 222 obese Korean children to determine whether it is associated with obesity. The frequencies of the Leu72Met polymorphism were 29.3% in obese, 32.3% in overweight, and 32.5% in lean Korean children. No significant difference was found between Met72 carrier and non-carrier obese children with respect to BMI, total body fat, serum triglycerides, total cholesterol, or LDL-cholesterol levels. Our data suggest that the preproghrelin Leu72Met polymorphism is not associated with obesity in children.

Gene polymorphisms against DNA damage induced by hydrogen peroxide in leukocytes of healthy humans through comet assay: a quasi-experimental study

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Klautau-Guimarães Maria N

2010-05-01

Full Text Available Abstract Background Normal cellular metabolism is well established as the source of endogenous reactive oxygen species which account for the background levels of oxidative DNA damage detected in normal tissue. Hydrogen peroxide imposes an oxidative stress condition on cells that can result in DNA damage, leading to mutagenesis and cell death. Several potentially significant genetic variants related to oxidative stress have already been identified, and angiotensin I-converting enzyme (ACE inhibitors have been reported as possible antioxidant agents that can reduce vascular oxidative stress in cardiovascular events. Methods We investigate the influences of haptoglobin, manganese superoxide dismutase (MnSOD Val9Ala, catalase (CAT -21A/T, glutathione peroxidase 1 (GPx-1 Pro198Leu, ACE (I/D and gluthatione S-transferases GSTM1 and GSTT1 gene polymorphisms against DNA damage and oxidative stress. These were induced by exposing leukocytes from peripheral blood of healthy humans (N = 135 to hydrogen peroxide (H2O2, and the effects were tested by comet assay. Blood samples were submitted to genotyping and comet assay (before and after treatment with H2O2 at 250 μM and 1 mM. Results After treatment with H2O2 at 250 μM, the GPx-1 polymorphism significantly influenced results of comet assay and a possible association of the Pro/Leu genotype with higher DNA damage was found. The highest or lowest DNA damage also depended on interaction between GPX-1/ACE and Hp/GSTM1T1 polymorphisms when hydrogen peroxide treatment increased oxidative stress. Conclusions The GPx-1 polymorphism and the interactions between GPX-1/ACE and Hp/GSTM1T1 can be determining factors for DNA oxidation provoked by hydrogen peroxide, and thus for higher susceptibility to or protection against oxidative stress suffered by healthy individuals.

Hypertension-Related Gene Polymorphisms of G-Protein-Coupled Receptor Kinase 4 Are Associated with NT-proBNP Concentration in Normotensive Healthy Adults

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Junichi Yatabe

2012-01-01

Full Text Available G protein-coupled receptor kinase 4 (GRK4 with activating polymorphisms desensitize the natriuric renal tubular D1 dopamine receptor, and these GRK4 polymorphisms are strongly associated with salt sensitivity and hypertension. Meanwhile, N-terminal pro-B-type natriuretic peptide (NT-proBNP may be useful in detecting slight volume expansion. However, relations between hypertension-related gene polymorphisms including GRK4 and cardiovascular indices such as NT-proBNP are not clear, especially in healthy subjects. Therefore, various hypertension-related polymorphisms and cardiovascular indices were analyzed in 97 normotensive, healthy Japanese adults. NT-proBNP levels were significantly higher in subjects with two or more GRK4 polymorphic alleles. Other hypertension-related gene polymorphisms, such as those of renin-angiotensin-aldosterone system genes, did not correlate with NT-proBNP. There was no significant association between any of the hypertension-related gene polymorphisms and central systolic blood pressure, cardioankle vascular index, augmentation index, plasma aldosterone concentration, or an oxidative stress marker, urinary 8-OHdG. Normotensive individuals with GRK4 polymorphisms show increased serum NT-proBNP concentration and may be at a greater risk of developing hypertension and cardiovascular disease.

The Leu33/Pro polymorphism (PlA1/PlA2) of the glycoprotein IIIa (GPIIIa) receptor is not related to myocardial infarction in the ECTIM Study. Etude Cas-Temoins de l'Infarctus du Myocarde.

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Herrmann, S M; Poirier, O; Marques-Vidal, P; Evans, A; Arveiler, D; Luc, G; Emmerich, J; Cambien, F

1997-06-01

The GPIIb/IIIa receptor complex may contribute to acute coronary syndromes by mediating platelet aggregation. The Leu33/Pro polymorphism (PlA1/PlA2) of the GPIIIa has recently been shown to be associated with CHD in a small case-control study. We have investigated this polymorphism in a large multicenter study of patients with myocardial infarction and controls and found no difference in the distribution of allele and genotype frequencies between cases and controls.

Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus.

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Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Park, Ji Hyun; Park, Sung Kwang; Yi, Ho Keun; Lee, Dae-Yeol

2006-03-01

Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.

Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

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Mager, U; Lindi, V; Lindström, J; Eriksson, J G; Valle, T T; Hämäläinen, H; Ilanne-Parikka, P; Keinänen-Kiukaanniemi, S; Tuomilehto, J; Laakso, M; Pulkkinen, L; Uusitupa, M

2006-06-01

Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016). Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.

Large-scale studies of the Leu72Met polymorphism of the ghrelin gene in relation to the metabolic syndrome and associated quantitative traits

DEFF Research Database (Denmark)

Bing, C; Ambye, L; Fenger, M

2005-01-01

Recently, low-frequency polymorphisms in the coding region of the ghrelin gene were suggested to be involved in the aetiology of obesity and to modulate glucose-induced insulin secretion in different ethnic study groups. The objective of the present large study was to investigate whether the Leu7...

The Leu72Met Polymorphism of the Prepro-ghrelin Gene is Associated With Alcohol Consumption and Subjective Responses to Alcohol: Preliminary Findings.

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Suchankova, Petra; Yan, Jia; Schwandt, Melanie L; Stangl, Bethany L; Jerlhag, Elisabet; Engel, Jörgen A; Hodgkinson, Colin A; Ramchandani, Vijay A; Leggio, Lorenzo

2017-07-01

The orexigenic peptide ghrelin may enhance the incentive value of food-, drug- and alcohol-related rewards. Consistent with preclinical findings, human studies indicate a role of ghrelin in alcohol use disorders (AUD). In the present study an a priori hypothesis-driven analysis was conducted to investigate whether a Leu72Met missense polymorphism (rs696217) in the prepro-ghrelin gene (GHRL), is associated with AUD, alcohol consumption and subjective responses to alcohol. Association analysis was performed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinical sample, comprising AUD individuals and controls (N = 1127). Then, a post-hoc analysis using data from a human laboratory study of intravenous alcohol self-administration (IV-ASA, N = 144) was performed to investigate the association of this SNP with subjective responses following a fixed dose of alcohol (priming phase) and alcohol self-administration (ad libitum phase). The case-control study revealed a trend association (N = 1127, OR = 0.665, CI = 0.44-1.01, P = 0.056) between AUD diagnosis and Leu72Met. In AUD subjects, the SNP was associated with significantly lower average drinks per day (n = 567, β = -2.49, 95% CI = -4.34 to -0.64, P = 0.008) and significantly fewer heavy drinking days (n = 567, β = -12.00, 95% CI = -19.10 to -4.89, P polymorphism in the prepro-ghrelin gene, is associated with alcohol use disorder, alcohol consumption and subjective responses to alcohol. Although preliminary, results suggest that the Leu72Leu genotype may lead to increased risk of alcohol use disorder possibly via mechanisms involving a lower response to alcohol. Medical Council on Alcohol and Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus.

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Zhuang, Langen; Li, Ming; Yu, Changhua; Li, Can; Zhao, Mingming; Lu, Ming; Zheng, Taishan; Zhang, Rong; Zhao, Weijing; Bao, Yuqian; Xiang, Kunsan; Jia, Weiping; Wang, Niansong; Liu, Limei

2014-02-01

The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case-control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.

Leu72Met and Other Intronic Polymorphisms in the and Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population

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Faris Elbahi Joatar; Ali Ahmed Al Qarni; Muhalab E. Ali; Abdulaziz Al Masaud; Abdirashid M. Shire; Nagalla Das; Khalid Gumaa; Hayder A. Giha

2017-01-01

Background Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associatio...

A Sordaria macrospora mutant lacking the leu1 gene shows a developmental arrest during fruiting body formation.

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Kück, Ulrich

2005-10-01

Developmental mutants with defects in fruiting body formation are excellent resources for the identification of genetic components that control cellular differentiation processes in filamentous fungi. The mutant pro4 of the ascomycete Sordaria macrospora is characterized by a developmental arrest during the sexual life cycle. This mutant generates only pre-fruiting bodies (protoperithecia), and is unable to form ascospores. Besides being sterile, pro4 is auxotrophic for leucine. Ascospore analysis revealed that the two phenotypes are genetically linked. After isolation of the wild-type leu1 gene from S. macrospora, complementation experiments demonstrated that the gene was able to restore both prototrophy and fertility in pro4. To investigate the control of leu1 expression, other genes involved in leucine biosynthesis specifically and in the general control of amino acid biosynthesis ("cross-pathway control") have been analysed using Northern hybridization and quantitative RT-PCR. These analyses demonstrated that genes of leucine biosynthesis are transcribed at higher levels under conditions of amino acid starvation. In addition, the expression data for the cpc1 and cpc2 genes indicate that cross-pathway control is superimposed on leucine-specific regulation of fruiting body development in the leu1 mutant. This was further substantiated by growth experiments in which the wild-type strain was found to show a sterile phenotype when grown on a medium containing the amino acid analogue 5-methyl-tryptophan. Taken together, these data show that pro4 represents a novel mutant type in S. macrospora, in which amino acid starvation acts as a signal that interrupts the development of the fruiting body.

Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity.

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Miraglia del Giudice, E; Santoro, N; Cirillo, G; Raimondo, P; Grandone, A; D'Aniello, A; Di Nardo, M; Perrone, L

2004-03-01

To test whether ghrelin variants could play a role in modulating some aspects of the obese phenotype during childhood. We screened the ghrelin gene in 300 Italian obese children and adolescents (mean age 10.5+/-3.2 y; range 4-19 y) and 200 controls by using the single-strand conformation polymorphism and the restriction fragment length polymoprhism analysis. No mutations were detected with the exception of two previously described polymorphisms, Arg51Gln and Leu72Met. For both variations, allelic frequencies were similar between patients and controls. Interestingly, we showed that the Leu72Met polymorphism was associated with differences in the age at obesity onset. Patients with the Met72 allele became obese earlier than homozygous patients for the wild Leu72 allele. The logrank test comparing the plots of the complement of Kaplan-Meier estimates between the two groups of patients was statistically significant (Pghrelin variations cause the obesity due to single-gene mutations. The Leu72Met polymorphism of the ghrelin gene seems to play a role in anticipating the onset of obesity among children suggesting, therefore, that ghrelin may be involved in the pathophysiology of human adiposity.

High plasma ghrelin protects from coronary heart disease and Leu72Leu polymorphism of ghrelin gene from cancer in healthy adults during the 19 years follow-up study.

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Laurila, M; Santaniemi, M; Kesäniemi, Y A; Ukkola, O

2014-11-01

The aim of our investigation was to find out if ghrelin concentrations or polymorphisms predict the future risk for cardiovascular diseases and cancer in a population-based cohort initiated in 1991 (491 hypertensive and 513 control subjects). Total mortality and hospital events were followed up for 19 years. Fasting total ghrelin concentrations were determined and Arg51Gln, Leu72Met and -501 A > C polymorphisms identified. Cox regression analysis was performed. The mean value in the control cohort was 674 pg/ml whereas in the hypertensive cohort it was 661 pg/ml. The associations found suggest that in the controls the highest ghrelin quartile protected from CHD (coronary heart disease). The results were significant without or with adjustments for age, sex, smoking, systolic blood pressure and LDL cholesterol, BMI, type 2 diabetes or QUICK index. C/C variant of the promoter associated with the prevention of IHD (ischemic heart disease) in the hypertensive group (pghrelin concentration was related to protection from CHD and Leu72Leu genotype to prevention of cancer in healthy adults during the 19 years follow-up. C/C promoter protects from IHD in the hypertensive subjects. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessment of the Pro12Ala Polymorphism in the PPAR-γ2 Gene among Type 2 Diabetes Patients in a Nigerian Population

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Godwill Azeh Engwa

2018-04-01

Full Text Available The association between the Pro12Ala polymorphism of the PPARγ2 gene, type 2 diabetes (T2D, and obesity in certain ethnic populations has been reported. However, this relationship has not yet been described among diabetes patients in Nigeria. This study investigated the relationship between the Pro12Ala polymorphism in the PPARγ2 gene, obesity, and lipid abnormalities characterizing T2D among patients in Nigeria. This case-control study recruited 73 T2D and 75 non-diabetic (ND patients. Demographic and clinical data were collected and blood glucose levels together with serum lipid profile for patients were measured. Pro12Ala polymorphism in the PPARγ2 gene was genotyped by restriction fragment length-Polymerase Chain Reaction (RFLP-PCR. The PPAR-γ2 gene (amplicon size = 270 base pair was successfully amplified for all samples. Following restriction enzyme digestion and analysis by agarose gel electrophoresis, amplicons from samples showed a band of size 270 bp and were of the wild homozygous Pro/Pro genotype. Ala12 variant was totally absent from the study population. Obesity, estimated using Body Mass Index (BMI and waist circumference (WC, was significantly higher (p < 0.05 in T2D patients compared to the non-diabetic patients. More so, the prevalence of lipid abnormalities; hypercholesterolaemia (TC > 200 mg/dL, hypertriglyceridaemia (TG > 150 mg/dL, high HDL (>100 mg/dL, and low HDL (<50 mg/dL was significantly greater (p < 0.001 in T2D patients compared to non-diabetic patients. Results obtained further indicated lack of significant association between PPAR-γ2 gene polymorphism, T2D, and obesity. However, obesity and dyslipidaemia were strongly associated in T2D patients.

Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study

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Okada Rieko

2012-01-01

Full Text Available Abstract Background The aim of this study was to explore the associations between common potential functional promoter polymorphisms in pro-/anti-inflammatory cytokine genes and kidney function/chronic kidney disease (CKD prevalence in a large Japanese population. Methods A total of 3,323 subjects aged 35-69 were genotyped for all 10 single nucleotide polymorphisms (SNPs in the promoter regions of candidate genes with minor allele frequencies of > 0.100 in Japanese populations. The estimated glomerular filtration rate (eGFR and CKD prevalence (eGFR 2 of the subjects were compared among the genotypes. Results A higher eGFR and lower prevalence of CKD were observed for the homozygous variants of IL4 -33CC (high IL-4 [anti-inflammatory cytokine]-producing genotype and IL6 -572GG (low IL-6 [pro-inflammatory cytokine]-producing genotype. Subjects with IL4 CC + IL6 GG showed the highest mean eGFR (79.1 ml/min/1.73 m2 and lowest CKD prevalence (0.0%, while subjects carrying IL4 TT + IL6 CC showed the lowest mean eGFR (73.4 ml/min/1.73 m2 and highest CKD prevalence (17.9%. Conclusions The functional promoter polymorphisms IL4 T-33C (rs2070874 and IL6 C-572G (rs1800796, which are the only SNPs that affect the IL-4 and IL-6 levels in Japanese subjects, were associated with kidney function and CKD prevalence in a large Japanese population.

A new variation in the promoter region, the -604 C>T, and the Leu72Met polymorphism of the ghrelin gene are associated with protection to insulin resistance.

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Zavarella, S; Petrone, A; Zampetti, S; Gueorguiev, M; Spoletini, M; Mein, C A; Leto, G; Korbonits, M; Buzzetti, R

2008-04-01

Previous studies suggested that polymorphisms in the coding region of the preproghrelin were involved in the etiology of obesity and might modulate glucose-induced insulin secretion. We evaluated the association of a new variation, -604C>T, in the promoter region of the ghrelin gene, of Leu72Met (247C>A) and of Gln90Leu (265A>T), all haplotype-tagging single nucleotide polymorphisms (SNPs), with measures of insulin sensitivity in 1420 adult individuals. The three SNPs were genotyped using ABI PRISM 7900 HT Sequence Detection System. We used multiple linear regression analysis for quantitative traits and THESIAS software for haplotype analysis. We observed a protective effect exerted by Met72 variant of Leu72Met SNP on insulin resistance parameters; a significant decreasing trend from Leu/Leu to Leu/Met and to Met/Met homozygous subjects in triglycerides, fasting insulin levels and HOMA-IR index (P=0.02, 0.01 and 0.003, respectively), and, consistently, an increase in ghrelin levels (P=0.003) was found. A significant decrease from CC to TC and to TT genotypes in insulin levels and HOMA-IR index was also detected (P=0.00l for both), but only in subjects homozygous for Leu72, where the protective effect of Met72 was not present. The haplotype analysis results supported the data obtained by the evaluation of each single SNP, showing the highest value of insulin levels and HOMA-IR index in the -604(c)247(c) haplotype intermediate value in -604(T)247(C) and lowest value in -604(C)247(A). Our observations suggest a protective role of the Met72 variant and of -604 T allele in modulating insulin resistance. These SNPs or an unknown functional variant in linkage disequilibrium could increase ghrelin levels and probably insulin sensitivity.

Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

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Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang

2006-07-01

Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

PPAR2Pro12Ala Polymorphism and Human Health

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Weimin He

2009-01-01

Full Text Available The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPAR is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPAR have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPAR, Pro12Ala of PPAR2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPAR2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPAR2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPAR2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies.

Peroxisome proliferator activated receptor gamma polymorphism Pro12Ala in polycystic ovary syndrome (PCOS of South Indian Population

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Raichel Jacob

2016-05-01

Conclusion: PPARγ2 gene Pro12Ala polymorphism was supposed to be susceptible genes in PCOS. The present study demonstrated that there is a statistical difference between the distributions of PPAR gamma Pro12Ala polymorphism in South Indian Population.

Dysregulated autophagy in restrictive cardiomyopathy due to Pro209Leu mutation in BAG3.

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Schänzer, A; Rupp, S; Gräf, S; Zengeler, D; Jux, C; Akintürk, H; Gulatz, L; Mazhari, N; Acker, T; Van Coster, R; Garvalov, B K; Hahn, A

2018-03-01

Myofibrillary myopathies (MFM) are hereditary myopathies histologically characterized by degeneration of myofibrils and aggregation of proteins in striated muscle. Cardiomyopathy is common in MFM but the pathophysiological mechanisms are not well understood. The BAG3-Pro209Leu mutation is associated with early onset MFM and severe restrictive cardiomyopathy (RCM), often necessitating heart transplantation during childhood. We report on a young male patient with a BAG3-Pro209Leu mutation who underwent heart transplantation at eight years of age. Detailed morphological analyses of the explanted heart tissue showed intracytoplasmic inclusions, aggregation of BAG3 and desmin, disintegration of myofibers and Z-disk alterations. The presence of undegraded autophagosomes, seen by electron microscopy, as well as increased levels of p62, LC3-I and WIPI1, detected by immunohistochemistry and western blot analyses, indicated a dysregulation of autophagy. Parkin and PINK1, proteins involved in mitophagy, were slightly increased whereas mitochondrial OXPHOS activities were not altered. These findings indicate that altered autophagy plays a role in the pathogenesis and rapid progression of RCM in MFM caused by the BAG3-Pro209Leu mutation, which could have implications for future therapeutic strategies. Copyright © 2018 Elsevier Inc. All rights reserved.

Polymorphisms of the ghrelin/obestatin gene and ghrelin levels in Chinese children with short stature.

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Zou, Chao Chun; Huang, Ke; Liang, Li; Zhao, Zheng Yan

2008-07-01

To investigate the role of ghrelin and polymorphisms of ghrelin/obestatin gene in children with short stature. A total of 117 GH deficient (GHD) and 81 idiopathic short stature (ISS) children were studied. The controls consisted of 125 age and gender-matched healthy children. The Arg51Gln, Leu72Met and Gln90Leu polymorphisms were genotyped using MassArray and total plasma ghrelin was measured by radioimmunoassay. In this study, the frequency of the Arg51Gln polymorphism was very low (0% in controls and 1.0% in patients). The frequency of the Gln90Leu polymorphism was 1.6% in controls and 0.5% in patients, respectively. Higher frequencies of Leu72Met (34.4% in controls and 39.9% in patients) and Met72Met genotypes (4.0% in controls and 2.0% in patients) were found. The differences in the Arg51Gln, Leu72Met or Gln90Leu genotypes and allele frequencies between patients and controls were not significant. Also, there were no significant differences in the Leu72Met genotypes and allele frequencies between GHD and ISS subgroups. There were no significant differences in clinical characteristics and biochemistry markers (including ghrelin levels) among the different genotypes of Leu72Met. However, plasma ghrelin levels in the GHD group were significantly lower than those of controls (P = 0.001). These results suggest that ghrelin may have a role in GH secretion and controlling growth. Lower ghrelin levels, but not ghrelin/obestatin polymorphism, might contribute to GHD.

The impact of GPX1 on the association of groundwater selenium and depression: a project FRONTIER study

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Johnson Leigh A

2013-01-01

Full Text Available Abstract Background Prior animal model and human-based studies have linked selenium concentrations to decreased risk for depression; however, this work has not focused on household groundwater levels or specific depressive symptoms. The current study evaluated the link between groundwater selenium levels and depression. We also sought to determine if a functional polymorphism in the glutathione peroxidase 1 (GPX1 gene impacted this link. Methods We used a cross-sectional design to analyze data from 585 participants (183 men and 402 women from Project FRONTIER, a study of rural health in West Texas. Residential selenium concentrations were estimated using Geospatial Information System (GIS analyses. Linear regression models were created using Geriatric Depression Scale (GDS-30 total and subfactor scores as outcome variables and selenium concentrations as predictor variables. Analyses were re-run after stratification of the sample on GPX1 Pro198Leu genotype (rs1050454. Results Selenium levels were significantly and negatively related to all GDS and subfactor scores accounting for up to 17% of the variance beyond covariates. Selenium was most strongly protective against depression among homozygous carriers of the C allele at the Pro198Leu polymorphism of the GPX1 gene. Analyses also point towards a gene-environmental interaction between selenium exposure and GPX1 polymorphism. Conclusion Our results support the link between groundwater selenium levels and decreased depression symptoms. These findings also highlight the need to consider the genetics of the glutathione peroxidase system when examining this relationship, as variation in the GPX1 gene is related to depression risk and significantly influences the protective impact of selenium, which is indicative of a gene-environment interaction.

TGFβ1 polymorphisms and late clinical radiosensitivity in patients treated for gynecologic tumors

International Nuclear Information System (INIS)

Ruyck, Kim de; Van Eijkeren, Marc; Claes, Kathleen; Bacher, Klaus; Vral, Anne; Neve, Wilfried de; Thierens, Hubert

2006-01-01

Purpose: To investigate the association between six transforming growth factor β1 gene (TGFβ1) polymorphisms (-1.552delAGG, -800G>A, -509C>T, Leu10Pro, Arg25Pro, Thr263Ile) and the occurrence of late normal tissue reactions after gynecologic radiotherapy (RT). Methods and Materials: Seventy-eight women with cervical or endometrial cancer and 140 control individuals were included in the study. According to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAEv3.0) scale, 25 patients showed late adverse RT reactions (CTC2+), of whom 11 had severe complications (CTC3+). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single base extension and genotyping assays were performed to examine the polymorphic sites in TGFβ1. Results: Homozygous variant -1.552delAGG, -509TT, and 10Pro genotypes were associated with the risk of developing late severe RT reactions. Triple (variant) homozygous patients had a 3.6 times increased risk to develop severe RT reactions (p = 0.26). Neither the -800A allele, nor the 25Pro allele or the 263Ile allele were associated with clinical radiosensitivity. There was perfect linkage disequilibrium (LD) between the -1.552delAGG and the -509C>T polymorphisms, and tight LD between the -1.552/-509 and the Leu10Pro polymorphisms. Haplotype analysis revealed two major haplotypes but could not distinguish radiosensitive from nonradiosensitive patients. Conclusions: The present study shows that homozygous variant TGFβ1 -1.552delAGG, -509TT, and 10Pro genotypes may be associated with severe clinical radiosensitivity after gynecologic RT

Relationships between the functional PPARalpha Leu162Val polymorphism and obesity, type 2 diabetes, dyslipidaemia, and related quantitative traits in studies of 5799 middle-aged white people

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Sparsø, Thomas; Hussain, Meena S; Andersen, Gitte

2007-01-01

Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a nuclear receptor capable of regulating the expression of genes involved in peroxisomal and mitochondrial beta-oxidation pathways. The common Leu162Val polymorphism in the gene encoding PPARalpha has inconsistently shown association...

Leu72Met and Other Intronic Polymorphisms in the and Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population

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Faris Elbahi Joatar

2017-09-01

Full Text Available BackgroundGhrelin (GHRL, a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs, namely the Leu72Met polymorphism (rs696217 TG, with type 2 diabetes mellitus (T2DM and insulin resistance (IR, while others have not. The controversies in these associations raise the issue of ‘which SNPs in which populations.’ The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis.MethodsBlood was collected from 208 Saudi subjects with (n=107 and without (n=101 T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT and GHSR (rs509030 GC genes. In addition, plasma GHRL levels were measured by a radioimmunoassay.ResultsNone of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region.ConclusionNeither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR.

Lack of association between the Pro12Ala polymorphism of the PPAR-gamma 2 gene and type 2 diabetes mellitus in the Qatari consanguineous population.

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Badii, Ramin; Bener, Abdulbari; Zirie, Mahmoud; Al-Rikabi, Ammar; Simsek, Mehmet; Al-Hamaq, Abdulla O A A; Ghoussaini, Maya; Froguel, Philippe; Wareham, Nick J

2008-03-01

Peroxisome proliferators-activated receptor gamma (PPAR gamma) is a nuclear hormone receptor that serves as a master regulator for adipocytes-specific genes contributing to adipocytes differentiation, insulin sensitivity and lipid metabolism. The substitution of proline to alanine at codon 12 of the PPAR gamma 2 gene (Pro12Ala polymorphism) is most widely studied, and the associations with diabetes, obesity, and other clinical parameters have been reported and discussed in several ethnic groups. Among native Qatar ethnicity, however, there is no report about this polymorphism. The aim of this study was to estimate the allele frequency of the Pro12Ala polymorphism of PPAR gamma 2 gene among Qatari population and investigate the association between this polymorphism and obesity or type 2 diabetes. This is a matched case-control study. It was carried out among diabetic patients and healthy subjects at the Primary Healthcare Clinics, and the survey was conducted from February 2003 to March 2006 in Qatari male and female nationals aged 35 to 60 years. The study was based on matched age, sex, and ethnicity of 400 cases (with diabetes) and 450 controls (without diabetes). Face-to-face interviews were based on a questionnaire that included variables such as age, sex, sociodemographic status, body mass index (BMI), and obesity. Their health status was assessed by medical conditions, family history, and blood pressure measurements. The allele frequency of Pro12Ala polymorphism in PPAR gamma 2 gene among Qataris is lower than that in many Caucasian ethnic groups. No association is seen between the Pro12Ala and type 2 Diabetes (0.055 vs 0.059, OR = 1.1311, P = 0.669). Nearly half of the diabetic type 2 patients (48.5%) were obese (BMI > 30) compared to nondiabetic subjects (29.8%) (P Qatar.

Plasma ghrelin levels and polymorphisms of ghrelin gene in Chinese obese children and adolescents.

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Zhu, J F; Liang, L; Zou, C C; Fu, J F

2010-09-01

To evaluate the role of fasting plasma ghrelin levels [ln(ghrelin)] and polymorphisms of ghrelin gene in Chinese obese children. Genotyping for ghrelin polymorphism was performed in 230 obese and 100 normal weight children. Among them, plasma ghrelin levels were measured in 91 obese and 23 health subjects. (1) Bivariate correlation analysis showed the ln(ghrelin) was inversely correlated with abnormality of glucose metabolism (r = -0.240, P = 0.023). Stepwise multiple regression analysis showed that abnormality of glucose metabolism was an independent determinant of plasma ghrelin levels (P = 0.023). (2) There was no difference in frequency of Leu72Met polymorphisms between obese and control groups (36.09 vs. 41.00%). Ghrelin is associated with obesity in childhood, especially associated with the glucose homeostasis. Lower ghrelin levels might be a result of obesity, but not a cause of obesity. The Leu72Met polymorphism of ghrelin gene is not associated with obesity and metabolic syndrome in Chinese children.

Leu72Met and Other Intronic Polymorphisms in the GHRL and GHSR Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population.

Science.gov (United States)

Joatar, Faris Elbahi; Al Qarni, Ali Ahmed; Ali, Muhalab E; Al Masaud, Abdulaziz; Shire, Abdirashid M; Das, Nagalla; Gumaa, Khalid; Giha, Hayder A

2017-09-01

Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associations raise the issue of 'which SNPs in which populations.' The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis. Blood was collected from 208 Saudi subjects with (n=107) and without (n=101) T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT) and GHSR (rs509030 GC) genes. In addition, plasma GHRL levels were measured by a radioimmunoassay. None of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region. Neither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR. Copyright © 2017 Korean Endocrine Society

Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure. The Etude Cas-Témoin de l'Infarctus du Myocarde (ECTIM) Study.

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Cambien, F; Ricard, S; Troesch, A; Mallet, C; Générénaz, L; Evans, A; Arveiler, D; Luc, G; Ruidavets, J B; Poirier, O

1996-11-01

Transforming growth factor-beta 1 (TGF-beta 1) plays an important role in the modulation of cellular growth and differentiation and the production and degradation of the extracellular matrix. A number of experimental results suggest that TGF-beta 1 may be involved in cardiovascular physiopathology. In the present study, we assessed whether the TGF-beta 1 gene is a candidate gene for coronary heart disease or hypertension. We screened the coding region and 2181 bp upstream of the TGF-beta gene for polymorphisms and identified seven polymorphisms: 3 in the upstream region of the gene at positions -988, -800, and -509 from the first transcribed nucleotide; 1 in a nontranslated region at position +72; 2 in the signal peptide sequence Leu10-->Pro, Arg25-->Pro; and 1 in the region of the gene coding for the precursor part of the protein not present in the active form, Thr263-->Ile. We analyzed these TGF-beta 1 polymorphisms in 563 patients with myocardial infarction and 629 control subjects from four regions in Northern Ireland and France. The Pro25 allele was more frequent in patients than in control subjects in Belfast (P < .01) and Strasbourg (P < .05). The TGF-beta 1 polymorphisms were not associated with the degree of angiographically assessed coronary artery disease in patients. The presence of a Pro25 allele was associated with a lower systolic pressure in the four control groups (P < .002), and a history of hypertension was significantly less frequent in homozygotes or heterozygotes for Pro25 than in hormozygotes for Arg25 (odds ratio, 0.43, 95% confidence interval, 0.19 to 0.92; P < .03). Since the Pro25 allele was associated with an increased risk of myocardial infarction and a reduced risk of hypertension, we favor a cautious interpretation of these apparently inconsistent results. Other studies will need to verify whether these associations are real.

TOLL-LIKE RECEPTOR 7 GENE Gln11Leu MISSENSEMUTATION AND SUSCEPTIBILITY TO PSORIASIS

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E. S. Galimova

2017-01-01

Full Text Available Toll-like receptor (TLR are responsible for recognizing various molecular patterns associated with pathogens. Their expression have been detected in skin cells such as keratinocytes and melanocytes. Numerous experimental studies demonstrate the key role of TLRs in the pathogenesis of immune diseases, including psoriasis. The objective of this study is to analyze the associations of polymorphisms in TLR7 gene and the risk of psoriasis development. DNA samples were collected from 138 patients with psoriasis and 317 healthy controls. Genotyping of rs179003, rs179008, rs179020, rs850632, rs12013728 polymorphic loci in TLR7 gene was performed using the SNPlex™method (AB, USA. SNP in the TLR7 gene rs179008 (Gln11Leu was associated with psoriasis in entire psoriasis, late onset and sporadic subgroups (Рс = 0.0065, OR = 1.95; Рс = 0.0004, OR = 2.50; Рс = 0.0078, OR = 2.2, respectively. In conclusion, this study is the first to identify genetic variants of the TLR7 gene significantly associated with psoriasis. 

TOLL-LIKE RECEPTOR 7 GENE Gln11Leu MISSENSEMUTATION AND SUSCEPTIBILITY TO PSORIASIS

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E. S. Galimova

2017-01-01

Full Text Available Toll-like receptor (TLR are responsible for recognizing various molecular patterns associated with pathogens. Their expression have been detected in skin cells such as keratinocytes and melanocytes. Numerous experimental studies demonstrate the key role of TLRs in the pathogenesis of immune diseases, including psoriasis. The objective of this study is to analyze the associations of polymorphisms in TLR7 gene and the risk of psoriasis development. DNA samples were collected from 138 patients with psoriasis and 317 healthy controls. Genotyping of rs179003, rs179008, rs179020, rs850632, rs12013728 polymorphic loci in TLR7 gene was performed using the SNPlex™method (AB, USA. SNP in the TLR7 gene rs179008 (Gln11Leu was associated with psoriasis in entire psoriasis, late onset and sporadic subgroups (Рс = 0.0065, OR = 1.95; Рс = 0.0004, OR = 2.50; Рс = 0.0078, OR = 2.2, respectively. In conclusion, this study is the first to identify genetic variants of the TLR7 gene significantly associated with psoriasis.

Meta-analysis of association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene and diabetic retinopathy in Caucasians and Asians.

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Ma, Jinlan; Li, Yan; Zhou, Fang; Xu, Xiaoyi; Guo, Gang; Qu, Yi

2012-01-01

The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) gene is reported to be associated with diabetes. However, the gene's association with diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) has been investigated in numerous epidemiologic studies with controversial results. This meta-analysis aimed to collectively assess the association of the Pro12Ala polymorphism with DR in T2DM. An electronic literature search was conducted on PubMed, ISI Web of Knowledge, EMBASE, and the China National Knowledge Internet. A dominant model [(Pro/Ala +Ala/Ala) versus Pro/Pro] was used to ensure adequate statistical power. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effect model. Potential sources of heterogeneity and bias were explored. This meta-analysis included genotype data from 2,720 cases with DR and 2,450 controls free of DR from eight eligible publications. The results showed the Ala allele had a protective effect on DR in T2DM (OR=0.81; 95% CI: 0.68-0.98, p=0.03). There was no significant evidence against homogeneity (I(2)=46%, P(heterogeneity)=0.07). The sensitivity analysis showed a robust association of the Pro12Ala polymorphism with DR in T2DM after a study involving Caucasians that presented a big effect on heterogeneity (OR=0.75; 95% CI: 0.62-0.91, p=0.003) was excluded. Possible ethnic differences in the association of the Pro12Ala single nucleotide polymorphism and DR were demonstrated; a significant association was illustrated in the Caucasian subgroup (OR=0.74; 95% CI: 0.59-0.94, p=0.01) but was not found in the Asian subgroup (OR=0.77; 95% CI: 0.55-1.07, p=0.12). No publication bias was observed. This meta-analysis suggested a significant association exists between the Pro12Ala polymorphism and DR in T2DM with ethnic differences. The Ala allele had a significant protective effect against DR in T2DM.

Association of calcitonin receptor gene (CALCR) polymorphism with kidney stone disease in the population of West Bengal, India.

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Mitra, Pubali; Guha, Manalee; Ghosh, Sudakshina; Mukherjee, Sourav; Bankura, Biswabandhu; Pal, Dilip Kumar; Maity, Biswanath; Das, Madhusudan

2017-07-30

Kidney Stone Disease (KSD) is a complex urologic disorder with strong genetic constituent. Earlier association studies have indicated that the genetic polymorphisms are the potential cause of stone materialization; however unfortunately, the actual genetic signature is still unknown. Therefore, present study was aimed to investigate the potential contribution of two important polymorphisms of calcitonin receptor gene (CALCR): (i) rs1801197 (Leu447Pro) and (ii) rs1042138 (3'UTR+18C>T) in renal stone formation. Accordingly, we enrolled 152 patients registered with calcium-rich stone in kidney (case) and 144 corresponding age, sex and ethnicity matched healthy individuals (controls). Epidemiological and clinical data were recorded as well as peripheral blood sample was collected from each individual. Serum creatinine and urinary calcium level was found high in patients, compared to controls. Out of two studied polymorphisms, we have not found any significant association against the rs1042138 with KSD, nonetheless, significant high frequency (p=0.001; Odds ratio=1.81; 95% CI: 1.28-2.55) of risk allele T against the rs1801197 (T>C) in patient was noted. Moreover, significant association with KSD was noted by genotypic analysis of rs1801197 (Leu447Pro) in our population. Interestingly, male patients carrying TT genotype was found to be at high risk of stone formation, while no such association was observed in female patients. Altogether, present study indicated that the rs1042138 might not be used as a useful marker for susceptibility of kidney stone formation, whereas, the rs1801197 could definitely be considered as one of the risk factors for KSD in Indian population at least in West Bengal in particular. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between the ghrelin Leu72Met polymorphism and type 2 diabetes risk: a meta-analysis.

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Liao, Ning; Xie, Zi-Kang; Huang, Jian; Xie, Zheng-Fu

2013-04-01

Data on the association between the ghrelin Leu72Met polymorphism and type 2 diabetes are conflicting. A meta-analysis was performed on this topic. We searched for case-control studies using electronic databases (Medline and PubMed) and reference lists of studies. Odds ratios (OR) and 95% confidence intervals (CI) assuming dominant, recessive and homozygote comparison genetic models were calculated. Six case-control studies involving a total of 3417 cases and 3081 controls were included in this meta-analysis. No association was found between the ghrelin Leu72Met polymorphism and type 2 diabetes risk in the overall population in dominant, recessive and homozygote comparison models. However, in subgroup analyses stratified by ethnicity, we found that the risk for type 2 diabetes was decreased in subjects with Met72+ genotypes in Caucasians (OR=0.79, 95% CI: 0.64-0.98, P(z)=0.030). The ghrelin Leu72Met polymorphism was protective against type 2 diabetes in Caucasians. Future studies performed in larger sample size are needed to allow a more definitive conclusion. Copyright © 2012 Elsevier B.V. All rights reserved.

Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk

DEFF Research Database (Denmark)

Méplan, Catherine; Dragsted, Lars Ove; Ravn-Haren, Gitte

2013-01-01

Breast cancer (BC) is one of the most common cancers in women. Evidence suggests that genetic variation in antioxidant enzymes could influence BC risk, but to date the relationship between selenoproteins and BC risk remains unclear. In this report, a study population including 975 Danish cases...... and 975 controls matched for age and hormone replacement therapy (HRT) use was genotyped for five functional single nucleotide polymorphisms (SNPs) in SEPP1, GPX1, GPX4 and the antioxidant enzyme SOD2 genes. The influence of genetic polymorphisms on breast cancer risk was assessed using conditional...... logistic regression. Additionally pre-diagnosis erythrocyte GPx (eGPx) activity was measured in a sub-group of the population. A 60% reduction in risk of developing overall BC and ductal BC was observed in women who were homozygous Thr carriers for SEPP1 rs3877899. Additionally, Leu carriers for GPX1 Pro...

Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines.

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Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif

2015-05-15

Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM.

Lung cancer risk associated with Thr495Pro polymorphism of GHR in Chinese population.

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Cao, Guochun; Lu, Hongna; Feng, Jifeng; Shu, Jian; Zheng, Datong; Hou, Yayi

2008-04-01

The incidence of lung cancer has been increasing over recent decades. Previous studies showed that polymorphisms of the genes involved in carcinogen-detoxication, DNA repair and cell cycle control comprise risk factors for lung cancer. Recent observations revealed that the growth hormone receptor (GHR) might play important roles in carcinogenesis and Rudd et al. found that the Thr495Pro polymorphism of GHR was strongly associated with lung cancer risk in Caucasians living in the UK (OR = 12.98, P = 0.0019, 95% CI: 1.77-infinity). To test whether this variant of GHR would modify the risk of lung cancer in Chinese population, we compared the polymorphism between 778 lung cancer patients and 781 healthy control subjects. Our results indicate that the frequency of 495Thr (2.8%) allele in cases was significantly higher than in controls (OR = 2.04, P = 0.006, 95% CI: 1.21-3.42) which indicated this allele might be a risk factor for lung cancer. Further analyses revealed Thr495Pro variant was associated with lung cancer in the subpopulation with higher risk for lung cancer: male subpopulation, still-smokers subpopulation and the subpopulation with familial history of cancer. In different histological types of lung cancer, Thr495Pro SNP was significantly associated with small cell and squamous cell lung cancer, but not with adenocarcinoma, which suggested a potential interaction between this polymorphism and metabolic pathways related to smoking. The potential gene-environment interaction on lung cancer risk was evaluated using MDR software. A significant redundant interaction between Thr495Pro polymorphism and smoking dose and familial history of cancer was identified and the combination of genetic factors and smoking status or familial history of cancer barely increased the cancer risk prediction accuracy. In conclusion, our results suggested that the Thr495Pro polymorphism of GHR was associated with the risk of lung cancer in a redundant interaction with smoking and

A possible association between panic disorder and a polymorphism in the preproghrelingene.

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Hansson, Caroline; Annerbrink, Kristina; Nilsson, Staffan; Bah, Jessica; Olsson, Marie; Allgulander, Christer; Andersch, Sven; Sjödin, Ingemar; Eriksson, Elias; Dickson, Suzanne L

2013-03-30

The aim of the study was to investigate whether polymorphisms in the preproghrelin gene are associated with anxiety disorders, such as panic disorder, in humans. Panic disorder is a severe anxiety disorder, characterized by sudden attacks of intense fear or anxiety in combination with somatic symptoms. The preproghrelin gene codes for two gut-derived circulating peptides that have been linked to anxiety-like behaviour in rodents: ghrelin (an orexigenic, pro-obesity hormone) and obestatin. In the present study, we genotyped three missense mutations in the preproghrelin gene in 215 patients suffering from panic disorder and in 451 controls. The A allele of the rs4684677 polymorphism was significantly associated with panic disorder, while there were no significant associations with the two other polymorphisms studied. We conclude that the rs4684677 (Gln90Leu) polymorphism in the preproghrelin gene may be associated with increased risk of panic disorder. It will be important to confirm these findings in additional panic disorder patient groups. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Comparison of L-selectin blood level and gene polymorphism in tuberculosis patients with healthy individuals.

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Eini, Peyman; Shirvani, Maria; Hajilooi, Mehrdad; Esna-Ashari, Farzaneh

2018-02-12

The inflammatory response to Mycobacterium tuberculosis bacilli influences tuberculosis (TB) progression. In this study, we aimed to identify the Phe206Leu polymorphism and serum L-selectin level in TB patients, compared to healthy individuals. Ninety patients with a diagnosis of TB and 90 healthy controls were selected in this study. The serum L-selectin level was determined, using ELISA. L-selectin polymorphism was also evaluated using PCR. For data analysis, SPSS was used at a significance level of 0.05. According to the findings, the mean±SD age of the participants was 57.5 ± 18.4 and 56.5 ± 17.5 years in the TB and healthy groups, respectively. The TB group showed a significantly higher serum L-selectin level (1721.1 ± 330.9) versus the healthy controls (1624 ± 279). The L-selectin Phe allele frequencies were higher than the Leu allele frequencies in the main population, whereas the patients and controls were not significantly different. Eight (0.04%) subjects had Leu/Leu genotypes, 84 (46.6%) carried Phe/Leu genotypes, and 88 (48.8%) had Phe/Phe genotypes. Our results showed that the groups were not significantly different regarding L-selectin genotypes. TB patients had a significantly higher serum L-selectin level, compared to the controls. Based on the findings, the incidence of TB and L-selectin polymorphism in the Phe206Leu gene had no significant association. © 2018 Wiley Periodicals, Inc.

The progesterone receptor Val660→Leu polymorphism and breast cancer risk

International Nuclear Information System (INIS)

De Vivo, Immaculata; Hankinson, Susan E; Colditz, Graham A; Hunter, David J

2004-01-01

Recent evidence suggests a role for progesterone in breast cancer development and tumorigenesis. Progesterone exerts its effect on target cells by interacting with its receptor; thus, genetic variations, which might cause alterations in the biological function in the progesterone receptor (PGR), can potentially contribute to an individual's susceptibility to breast cancer. It has been reported that the PROGINS allele, which is in complete linkage disequilibrium with a missense substitution in exon 4 (G/T, valine→leucine, at codon 660), is associated with a decreased risk for breast cancer. Using a nested case-control study design within the Nurses' Health Study cohort, we genotyped 1252 cases and 1660 matched controls with the use of the Taqman assay. We did not observe any association of breast cancer risk with carrying the G/T (Val660→Leu) polymorphism (odds ratio 1.10, 95% confidence interval 0.93–1.30). In addition, we did not observe an interaction between this allele and menopausal status and family history of breast cancer as reported previously. Overall, our study does not support an association between the Val660→Leu PROGINS polymorphism and breast cancer risk

Associations of Leu72Met Polymorphism of Preproghrelin with Ratios of Plasma Lipids Are Diversified by a High-Carbohydrate Diet in Healthy Chinese Adolescents.

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Su, Mi; Qiu, Li; Wang, Qian; Jiang, Zhen; Liu, Xiao Juan; Lin, Jia; Fang, Ding Zhi

2015-01-01

The association of preproghrelin Leu72Met polymorphism with plasma lipids profile was inconsistently reported and needs more studies to be confirmed. Our study was to investigate the changes of plasma lipids ratios after a high-carbohydrate (high-CHO) diet in healthy Chinese adolescents with different genotypes of this polymorphism. Fifty-three healthy university students were given a washout diet of 54.1% carbohydrate for 7 days, followed by a high-CHO diet of 70.1% carbohydrate for 6 days. The anthropometric and biological parameters were analyzed at baseline and before and after the high-CHO diet. When compared with those before the high-CHO diet, body mass index (BMI) decreased in the male and female Met72 allele carriers. Decreased low-/high-density lipoprotein cholesterol (LDL-C/HDL-C) was observed in all participants except the female subjects with the Leu72Leu genotype. TG/HDL-C and log (TG/HDL-C) were increased only in the female subjects with the Leu72Leu genotype. These results suggest that the Met72 allele of preproghrelin Leu72Met polymorphism may be associated with decreased BMI induced by the high-CHO diet in male and female adolescents, while the Leu72 allele with increased TG/HDL-C and log (TG/HDL-C) in the female adolescents only. Furthermore, the decreasing effect of the high-CHO diet on LDL/HDL-C may be eliminated in the female Leu72Leu homozygotes. © 2015 S. Karger AG, Basel.

Identification of polymorphism in the SCL24A5 gene of cattle

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Paola Crepaldi

2010-01-01

Full Text Available The SLC24A5 (Solute Carrier family 24, member 5 gene is implicated in skin pigmentation in zebrafish and humans as it regulates the morphogenesis of melanosomes, specialized lysosomes involved in melanin deposit. In humans, the ancestral allele predominates in African and East Asian populations, while the allelic variant is nearly fixed in European populations and correlates with lighter pigmentation. Considering the role of melanin in the protecting of DNA from ultraviolet radiation, the lack of information in cattle and the importance of polymorphisms associated with pigmentation phenotypes, we investigated the SLC24A5 gene in cattle with light and dark skin pigmentation. To identify SNPs (Single Nucleotide Polymorphisms in this gene and their association to dark skin pigmentation in cattle, each of the nine SLC24A5 exons, three introns (1, 3 and 8 and a portion of intron 5, were sequenced in a set of sixteen animals belonging to four Italian cattle breeds, two African zebu breeds and two African sanga breeds. The region spanning exons 3 and 4 was sequenced in fifteen animals belonging to seven additional breeds. A total of sixteen SNPs were identified: eleven positioned in introns (six in intron 1, one in intron 5 and four in intron 8 and five in exons (one in exon 1, two in exon 6 and two in exon 7. Three SNPs (located in exons 1, 6 and 7 were non synonymous, determining Pro19Leu, Ala238Val, and Met341Ile amino acid changes, respectively. All the SNPs identified were polymorphic between Bos taurus, Bos indicus and Sanga, while none of them resulted associated with the studied phenotype and discriminated the three breeds (Chianina, Mucubal and Goudali characterized by dark pigmented skin from the others.

Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis.

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Dong, Zhiyong; Zheng, Longzhi; Liu, Weimin; Wang, Cunchuan

2018-01-01

The relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations. The association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI. We confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, P =0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, P =0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, P =0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, P =0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, P colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians.

Meat, milk, saturated fatty acids, the Pro12Ala and C161T polymorphisms of the PPARgamma gene and colorectal cancer risk in Japanese.

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Kuriki, Kiyonori; Hirose, Kaoru; Matsuo, Keitaro; Wakai, Kenji; Ito, Hidemi; Kanemitsu, Yukihide; Hirai, Takashi; Kato, Tomoyuki; Hamajima, Nobuyuki; Takezaki, Toshiro; Suzuki, Takeshi; Saito, Toshiko; Tanaka, Rie; Tajima, Kazuo

2006-11-01

The peroxisome proliferator-activated receptor gamma (PPARgamma) gene plays important roles in energy homeostasis. To examine interactions between consumption of foods and fatty acids and the Pro12Ala and C161T (His447His) polymorphisms for colorectal cancer, we performed two case-control studies in Japanese. In study 1, there were 128 colorectal cancer cases and 238 non-cancer controls, and in study 2 there were 257 cases and 771 (age- and sex-matched) non-cancer controls. Assessment of food and nutrients consumption in study 1 was via a nine-item questionnaire, while in study 2 assessment of consumption was according to a more detailed semiquantitative food frequency questionnaire. Consumption of foods and fatty acids was divided into low, moderate and high groups. The overall frequency of the Ala allele was frequencies of the Pro/Pro + C/C and Pro/Pro + (C/T + T/T) genotypes were 70-73% and 20-26%, respectively. Compared with subjects with low meat intake and the Pro/Pro + C/C genotype, those with high meat consumption and the same genotype had a stronger increased risk in study 1 [OR, 2.88; 95% CI, 1.14-7.30; P for trend = 0.02], but a positive association with processed meat consumption was greatest in those with the Pro/Pro + (C/T + T/T) genotype (P for trend = 0.05) in study 2. Likewise, high consumption of saturated fatty acids and milk appeared to confer marginal increased risk and stronger decreased risk, respectively, in those with the Pro/Pro and Pro/Pro + C/C genotypes (OR, 1.35 and 0.65; 95% CI, 0.93-1.96 and 0.43-1.00; P for trend = 0.10 and 0.06). Further large-scale studies are needed to determine colorectal cancer risk according to relationships between the PPARgamma gene polymorphisms and dietary intakes of meat, processed meat, milk and saturated fatty acids in Japanese with very low frequency of the Ala allele.

Polymorphism of the p53 tumor suppressor gene is associated with susceptibility to uterine leiomyoma.

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Denschlag, Dominik; Bettendorf, Herta; Watermann, Dirk; Keck, Christoph; Tempfer, Clemens; Pietrowski, Detlef

2005-07-01

To evaluate the association between the presence of uterine leiomyoma and two single nuclear polymorphisms of the p53 tumor suppressor and the angiopoietin-2 (ANGPT2) genes. Prospective case control study. Academic research institution. One hundred thirty-two women with clinically and surgically diagnosed uterine leiomyomas and 280 controls. Peripheral venous puncture. Genotyping was performed by polymerase chain reaction-based amplification of the Arg and Pro variants at codon 72 of the p53 gene and by restriction fragment length polymorphism analysis of the G/G and G/A alleles in exon 4 of the ANGPT2 gene. Comparing women with uterine leiomyomas and controls, no statistically significant difference with respect to allele frequency and genotype distribution were ascertained for the ANGPT2 polymorphism (P=.2 and P=.5, respectively). However, for the p53 tumor suppressor gene polymorphism, statistically significant differences in terms of a higher Pro allele frequency and a higher prevalence of the Pro/Pro genotype among women with uterine leiomyoma (32.0% vs. 16.0%, respectively, and 21.3% vs. 4.7%, respectively) were ascertained (P=.001, OR 1.74; 95% CI 1.24-2.45, P=.001; OR 3.84, 95% CI 1.81-8.14; respectively). Carriage of the p53 polymorphism at codon 72 predicts the susceptibility to leiomyoma in a Caucasian population and may contribute to the pathogenesis of uterine leiomyoma.

Ghrelin and obestatin plasma levels and ghrelin/obestatin prepropeptide gene polymorphisms in small for gestational age infants.

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Zhang, Shulian; Zhai, Guanpeng; Zhang, Jinping; Zhou, Jianguo; Chen, Chao

2014-12-01

To investigate plasma ghrelin and obestatin levels, and ghrelin/obestatin prepropeptide gene polymorphisms, in sequentially enrolled small for gestational age (SGA) infants. Neonates were sequentially enrolled into this study and were then subdivided into different groups, according to different study aims and availability of study materials. Consequently, plasma ghrelin and obestatin levels were measured in term SGA, term appropriate for gestational age (AGA), term large for gestational age (LGA), preterm SGA and preterm AGA neonates. Levels of both peptides were also measured in AGA infants of different gestational ages, and in term AGA neonates at different days following birth. Three ghrelin/obestatin prepropeptide gene single nucleotide polymorphisms (SNPs), Arg51Gln, Leu72Met, and Gln90Leu, were measured in neonates. The study involved a total cohort of 581 neonates. Out of 150 neonates (30 term AGA, 30 term SGA, 30 term LGA, 30 preterm AGA, and 30 preterm SGA), plasma obestatin levels were significantly higher in term SGA versus term LGA neonates (0.21 ± 0.02 ng/ml versus 0.17 ± 0.01 ng/ml, respectively). Out of a wider cohort, there were no significant differences in genotypes and allele frequencies of Arg51Gln, Leu72Met, and Gln90Leu SNPs between term SGA and AGA neonates, or between preterm SGA and AGA neonates. Ghrelin/obestatin prepropeptide polymorphisms were not found to be associated with SGA status in neonates; however, ghrelin and obestatin levels may be involved in growth and development. Further studies are required to understand the relationship between ghrelin, obestatin and prenatal development. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Association of ghrelin receptor gene polymorphism with bulimia nervosa in a Japanese population.

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Miyasaka, K; Hosoya, H; Sekime, A; Ohta, M; Amono, H; Matsushita, S; Suzuki, K; Higuchi, S; Funakoshi, A

2006-09-01

Eating disorders (EDs) have a highly heterogeneous etiology and multiple genetic factors might contribute to their pathogenesis. Ghrelin, a novel growth hormone-releasing peptide, enhances appetite and increases food intake, and human ghrelin plasma levels are inversely correlated with body mass index. In the present study, we examined the 171T/C polymorphism of the ghrelin receptor (growth hormone secretagogue receptor, GHSR) gene in patients diagnosed with EDs, because the subjects having ghrelin gene polymorphism (Leu72Met) was not detected in a Japanese population, previously. In addition, beta3 adrenergic receptor gene polymorphism (Try64Arg) and cholecystokinin (CCK)-A receptor (R) gene polymorphism (-81A/G, -128G/T), which are both associated with obesity, were investigated. The subjects consisted of 228 Japanese patients with EDs [96 anorexia nervosa (AN), 116 bulimia nervosa (BN) and 16 not otherwise specified (NOS)]. The age- and gender-matched control group consisted of 284 unrelated Japanese subjects. The frequency of the CC type of the GHSR gene was significantly higher in BN subjects than in control subjects (chi(2) = 4.47, p = 0.035, odds ratio = 2.05, Bonferroni correction: p = 0.070), while the frequency in AN subjects was not different from that in controls. The distribution of neither beta3 adrenergic receptor gene nor CCK-AR polymorphism differed between EDs and control subjects. Therefore, the CC type of GHSR gene polymorphism (171T/C) is a risk factor for BN, but not for AN.

Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women

OpenAIRE

Saliba,Louise F.; Reis,Rodrigo S.; Brownson,Ross C.; Hino,Adriano A.; Tureck,Luciane V.; Valko,Cheryl; Souza,Ricardo L.R. de; Furtado-Alle,Lupe

2014-01-01

The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713), ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (...

Analysis of Vitamin D Receptor (VDR Gene Polymorphisms in Alopecia Areata

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Omer Ates

2016-09-01

Full Text Available Aim: Alopecia areata (AA is a disease characterized with hair loss on the hair skin any region of the body. This disease affects approximately 1%u20132% of the general population. The etiopathogenesis of this disease is unclear but infections, genetic, psychological and autoimmune factors is known play to role. Vitamin D is thought to be a regulator of the immune system and the action of it is dependent on the vitamin D receptor (VDR. Given the autoimmune component shared by this autoimmune diseases. In this study investigated the role of VDR gene polymorphisms in the development of AA. Material and Method: The study group included 198 patients with AA and 167 control. Genomic DNA was extracted from blood samples using DNA isolation kit. The frequency of VDR gene polymorphisms genotypes and allelic variants were analyzed by using Polymerase Chain Reaction (PCR and Restriction Fragment Length Polymorphisms (RFLP method. Results: Statistical evaluation of data results showed a not significant association for genotypic frequency distribution between the VDR gene BsmI (rs1544410 and ApaI (rs7975232, TaqI (rs731236 polymorphisms and AA (p=0.8891, 0.7309, 0.6761, respectively. Discussion: Our study reflects that VDR gene polymorphisms could not play a role in determining genetic susceptibility to AA.

Study of five novel non-synonymous polymorphisms in human brain-expressed genes in a Colombian sample.

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Ojeda, Diego A; Forero, Diego A

2014-10-01

Non-synonymous single nucleotide polymorphisms (nsSNPs) in brain-expressed genes represent interesting candidates for genetic research in neuropsychiatric disorders. To study novel nsSNPs in brain-expressed genes in a sample of Colombian subjects. We applied an approach based on in silico mining of available genomic data to identify and select novel nsSNPs in brain-expressed genes. We developed novel genotyping assays, based in allele-specific PCR methods, for these nsSNPs and genotyped them in 171 Colombian subjects. Five common nsSNPs (rs6855837; p.Leu395Ile, rs2305160; p.Thr394Ala, rs10503929; p.Met289Thr, rs2270641; p.Thr4Pro and rs3822659; p.Ser735Ala) were studied, located in the CLOCK, NPAS2, NRG1, SLC18A1 and WWC1 genes. We reported allele and genotype frequencies in a sample of South American healthy subjects. There is previous experimental evidence, arising from genome-wide expression and association studies, for the involvement of these genes in several neuropsychiatric disorders and endophenotypes, such as schizophrenia, mood disorders or memory performance. Frequencies for these nsSNPSs in the Colombian samples varied in comparison to different HapMap populations. Future study of these nsSNPs in brain-expressed genes, a synaptogenomics approach, will be important for a better understanding of neuropsychiatric diseases and endophenotypes in different populations.

The value of polymorphism RRO12ALA gene PPARG in violation of lipid peroxidation and antioxidant protection in patients with type 2 diabetes mellitus

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S. V. Ziablytsev

2016-09-01

  Resume. The incidence of type 2 diabetes mellitus is increasing in Ukraine and worldwide. The severity of this disease is determined by the number of complications, which are based on lipid peroxidation (LPO. Today, the influence of gene polymorphisms Pro12Ala PPARG on oxidative and antioxidant processes is not in doubt. We studied the association between gene polymorphism Pro12Ala rs1801282 PPARG and intensification of lipid peroxidation and antioxidant systems (AOS in 88 patients with type 2 diabetes, using analysis of variance. In the 12Pro allele carriers male found probable increased intensification of lipid peroxidation than in women, with increasing levels of DC (p=0,034 and MDA (p=0,001. Reducing the enzyme catalase level of AOC in patients with type 2 diabetes was observed in the case of genotype Pro12Pro gene PPARG on 21.7% compared with heterozygotes (F=8,17; p=0,005 and the presence of the allele 12Pro (F=6,28 , p=0,013. Found significantly higher activity of AOC in the form of increasing the level of α-TF (p=0,016 and catalase activity (p=0,034 among male patients with gene polymorphism Pro12Ala PPARG, than homozygotes for allele 12Pro.   Key words: lipid peroxidation; antioxidant system; type 2 diabetes mellitus; polymorphism Pro12Ala rs1801282 of gene PPARG

Evidence for an association between the Leu162Val polymorphism of the PPARalpha gene and decreased fasting serum triglyceride levels in glucose tolerant subjects

DEFF Research Database (Denmark)

Nielsen, Eva-Maria D; Hansen, Lars; Echwald, Søren Morgenthaler

2003-01-01

The aim of the study was to investigate whether genetic variation in the peroxisome proliferator-activated receptor-alpha (PPARalpha) is associated with type 2 diabetes and altered lipid or carbohydrate metabolism in glucose tolerant subjects. Mutation analyses of PPARalpha were performed in 56...... type 2 diabetic patients. Six variants were identified: IVS3 + 76T>C, IVS3-19C>T, IVS4 + 35C>T, Leu162Val, Arg178Gly and Ala268Val. In a case-control study comprising 738 type 2 diabetic patients and 524 glucose tolerant subjects, the three exon variants did not show any significant differences...... in allele frequencies between type 2 diabetic patients and control subjects. The functional Leu162Val polymorphism was further investigated in genotype-phenotype studies involving 340 young, healthy subjects and 502 middle-aged glucose tolerant subjects. The young, healthy subjects who were heterozygous...

The Pro12Ala Polymorphism of PPAR-γ Gene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population

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Guoda Ma

2014-01-01

Full Text Available Peroxisome proliferator-activated receptor-γ (PPAR-γ is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P=0.622 for genotype; P=0.629 for allele. However, stratification by subtypes (sepsis, septic shock, and severe sepsis revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P=0.014 for allele and P=0.012, for genotype. Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P=0.002. In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P<0.001. Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.

Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue

International Nuclear Information System (INIS)

Antonov, Janine; Altermatt, Hans Jörg; Aebi, Stefan; Jaggi, Rolf; Popovici, Vlad; Delorenzi, Mauro; Wirapati, Pratyaksha; Baltzer, Anna; Oberli, Andrea; Thürlimann, Beat; Giobbie-Hurder, Anita; Viale, Giuseppe

2010-01-01

The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months. RNA from fresh frozen (FF) and FFPE tumor samples of 82 patients were used for quality control, and independent FFPE tissues of 342 postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by measuring prospectively selected genes and computing scores representing the functions of the estrogen receptor (eight genes, ER-8), the progesterone receptor (five genes, PGR-5), Her2 (two genes, HER2-2), and proliferation (ten genes, PRO-10) by quantitative reverse transcription PCR (qRT-PCR) on TaqMan Low Density Arrays. Molecular scores were computed for each category and ER-8, PGR-5, HER2-2, and PRO-10 scores were combined into a RISK-25 score. Pearson correlation coefficients between FF- and FFPE-derived scores were at least 0.94 and high concordance was observed between molecular scores and immunohistochemical data. The HER2-2, PGR-5, PRO-10 and RISK-25 scores were significant predictors of disease free-survival (DFS) in univariate Cox proportional hazard regression. PRO-10 and RISK-25 scores predicted DFS in patients with histological grade II breast cancer and in lymph node positive disease. The PRO-10 and PGR-5 scores were independent predictors of DFS in multivariate Cox regression models incorporating clinical risk indicators; PRO-10 outperformed Ki-67 labeling index in multivariate Cox proportional hazard analyses. Scores representing the endocrine responsiveness and proliferation status of breast cancers were developed from gene expression analyses based on RNA derived from FFPE tissues. The validation of the molecular scores with tumor samples of participants of the BIG 1-98 trial demonstrates that such scores can serve as independent prognostic factors to estimate disease free survival (DFS) in

EVALUATION OF CYTOKINE GENE POLYMORPHISM IN B CELL LYMPHOID MALIGNANCIES

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E. L. Nazarova

2014-01-01

Full Text Available Previous studies with some solid tumors has shown that polymorphisms of certain cytokine genes may be used as predictors of clinical outcome in the patients. It seemed important to evaluate potential correlations between production of certain pro- and anti-inflammatory cytokines and co-receptor molecules, and promoter polymorphism of the cytokine genes involved into regulation of cell proliferation, differentiation, apoptosis, lipid metabolism and blood clotting in the patients with hematological malignancies. The article contains our results concerning associations between of IL-1β, -2, -4, -10, -17, TNFα, and allelic polymorphisms of their genes in 62 patients with B cell lymphoid malignancies in an ethnically homogenous group (self-identified as Russians. We have shown that the GА and AA genotypes of the G-308A polymorphism in TNFα gene are significantly associated with increased production of this cytokine, being more common in aggressive non-Hodgkin lymphomas, more rare in multiple myeloma and in indolent non-Hodgkin lymphomas.

Gene Polymorphism and Left Ventricular Geometry and Function in Hypertensive Subjects

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Rosario Scaglione

2010-01-01

Full Text Available The distribution of the T29C TGFβ1 gene polymorphism was analyzed in 198 hypertensives with left ventricular hypertrophy (LVH and in 235 hypertensives without LVH. Circulating TGFβ1 levels, procollagen type III levels, microalbuminuria, and left ventricular geometry and function were evaluated in all the hypertensives with LVH subgrouped according to T29C TGFβ1 gene polymorphism. Circulating TGFβ1 was evaluated by ELISA technique, procollagen type III by a specific radioimmunoassay, microalbuminuria by radioimmunoassay, and left ventricular geometry and function by echocardiography. All groups were comparable for gender, age, and sex. Regarding T29C TGFβ1 gene polymorphism, prevalence of TC or CC genotypes was significantly (P<.05 higher in hypertensives with LVH than hypertensives without LVH TC and CC LVH hypertensives were characterized by a higher prevalence of subjects with microalbuminuria (P<.05 TC and CC versus TT, by increased levels of TGFβ1, procollagen type III, urinary albumin excretion, LVM, LVM/h2.7, and lower values of left ventricular ejection fraction (P<.05 TC and CC versus TT. Our data suggest that T29C TGFβ1 gene polymorphism was associated with clinical characteristics adequate to recognize a subset of LVH hypertensives with a higher severity of hypertension.

The (CTGn polymorphism in the NOTCH4 gene is not associated with schizophrenia in Japanese individuals

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Okubo Takehito

2001-06-01

Full Text Available Abstract Background The human NOTCH4 gene is a candidate gene for schizophrenia due to its chromosomal location and neurobiological roles. In a British linkage study, NOTCH4 gene polymorphisms were highly associated with schizophrenia. In a Japanese case-control association study, however, these polymorphisms did not show significant associations with schizophrenia. We conducted a case-control study with Japanese subjects to explore an association between the triplet repeat polymorphism in the NOTCH4 gene and schizophrenia, including subtypes of schizophrenia, longitudinal disease course characteristics, and a positive family history for psychoses. Methods We examined the (CTGn repeat polymorphism in the NOTCH4 gene among 100 healthy Japanese individuals and 102 patients with schizophrenia (22 paranoid, 38 disorganized, 29 residual, 64 episodic, 31 continuous, 42 with prominent negative symptoms, and 46 with positive family histories using a polymerase chain reaction-based, single-strand conformational polymorphism analysis. Results Five different alleles consisting of 6, 9, 10, 11, and 13 repeats of CTG (Leu in patients with schizophrenia, and 4 alleles consisting of 6, 9, 10, and 11 repeats in controls were found. No significant differences in genotype or allele frequencies of repeat numbers were found between controls and patients. In addition, there were no associations between the polymorphism and schizophrenia subtypes, longitudinal disease course characteristics, or positive family history of the patients. Conclusions Our data suggest a lack of association between the NOTCH4 gene triplet repeat polymorphism and schizophrenia in Japanese individuals.

PPARγ Pro12Ala and ACE ID polymorphisms are associated with BMI and fat distribution, but not metabolic syndrome

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Passaro Angela

2011-12-01

Full Text Available Abstract Background Metabolic Syndrome (MetS results from the combined effect of environmental and genetic factors. We investigated the possible association of peroxisome proliferator-activated receptor-γ2 (PPARγ2 Pro12Ala and Angiotensin Converting Enzyme (ACE I/D polymorphisms with MetS and interaction between these genetic variants. Methods Three hundred sixty four unrelated Caucasian subjects were enrolled. Waist circumference, blood pressure, and body mass index (BMI were recorded. Body composition was estimated by impedance analysis; MetS was diagnosed by the NCEP-ATPIII criteria. A fasting blood sample was obtained for glucose, insulin, lipid profile determination, and DNA isolation for genotyping. Results The prevalence of MetS did not differ across PPARγ2 or ACE polymorphisms. Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but lower systolic blood pressure compared with Pro/Pro homozygotes. A significant PPARγ2 gene-gender interaction was observed in the modulation of BMI, fat mass, and blood pressure, with significant associations found in women only. A PPARγ2-ACE risk genotype combination for BMI and fat mass was found, with ACE DD/PPARγ2 Ala subjects having a higher BMI (p = 0.002 and Fat Mass (p = 0.002. Pro12Ala was independently associated with waist circumference independent of BMI and gender. Conclusions Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but not a worse metabolic profile, possibly because of a more favorable adipose tissue distribution. A gene interaction exists between Pro12Ala and ACE I/D on BMI and fat mass. Further studies are needed to assess the contribution of Pro12Ala polymorphism in adiposity distribution.

Genotyping of PPAR-γ gene polymorphism in Egyptian neonates affected with sepsis disease and its severity

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Rabah M. Shawky

2018-07-01

Full Text Available Background: Peroxisome Proliferator-Activated Receptor gamma (PPARγ is a ligand-dependent transcription factor involved in inflammatory process. PPAR-γ gene was mentioned as having a modulating role in the pathological status of sepsis.The present study aimed to make a correlation between The Pro12Ala polymorphism in PPAR-γ gene and occurrence of neonatal sepsis and its severity among a sample of Egyptian neonates suffering sepsis. Subjects and methods: This case-control study included 30 neonates (11 females and19 males newly admitted with neonatal sepsis at the intensive care unit (NICU (mean age 10.3 days ± 6.23. The control group included 50 age and sex matched neonates (23 females and 27 males (mean age 10.20 days ± 5.36 days. All the neonates (preterm and full term included were with clinical signs and laboratory data consistent with neonatal sepsis. Genotyping for PPARγ gene region harboring the Pro12Ala variant locus were carried out using Tetra ARMS technique. Results: About 56.7% of the patients group was homozygote (GG for polymorphic locus (coding for Alanine/Alanine while 30% was heterozygote for polymorphic locus (CG (coding for Proline/Alanine and up to 13.3% was homozygote for the polymorphic locus (CC (coding for Proline/Proline. Compared to the control group where homozygotes for CC were the most prevalent (90% and the CG were 10% with absence of GG genotypes. There was a strong statistical significant difference between patients and the normal control group as regards prevalence of PPAR-γ gene polymorphism in occurrence of neonatal sepsis and its severity. Also, there were strong relation between genotype GG and low birth weight, neonatal fever, prematurity and depressed neonatal reflexes. Conclusion: PPAR-γ gene has been suggested to be a candidate gene for neonatal sepsis. Therefore, Pro12Ala polymorphism might be useful in predicting the risk factor of neonatal sepsis and its severity. Keywords: Sepsis, PPAR

Studies of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene in relation to insulin sensitivity among glucose tolerant caucasians

DEFF Research Database (Denmark)

Ek, J; Andersen, G; Urhammer, S A

2001-01-01

We examined whether the Pro12-Ala polymorphism of the human peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene was related to altered insulin sensitivity among glucose-tolerant subjects or a lower accumulated incidence or prevalence of IGT and Type II (non-insulin-dependent) dia......-insulin-dependent) diabetes mellitus among Scandinavian Caucasians....

Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: association with subtype, body-mass index, severity and age of onset.

Science.gov (United States)

Dardennes, Roland M; Zizzari, Philippe; Tolle, Virginie; Foulon, Christine; Kipman, Amélie; Romo, Lucia; Iancu-Gontard, Dana; Boni, Claudette; Sinet, Pierre-Marie; Thérèse Bluet, Marie; Estour, Bruno; Mouren, Marie-Christine; Guelfi, Julien-Daniel; Rouillon, Frédéric; Gorwood, Philip; Epelbaum, Jacques

2007-02-01

Anorexia nervosa (AN) affects 0.3% of young girls with a mortality of 6%/decade and is strongly familial with genetic factors. Ghrelin is an upstream regulator of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to leptin's effects on NPY/AgRP-expressing neurons, resulting in an increase in feeding and body weight. Obestatin which counteracts ghrelin action on feeding is derived from the same propeptide than ghrelin. BDNF has been involved in body weight regulation and its Val66Met polymorphism associated with AN. We therefore re-investigated the association between AN and the Leu72Met and Gln90Leu polymorphisms of the prepro-ghrelin/obestatin gene, the Ala67Thr polymorphism of AgRP and the Val66Met polymorphism of BDNF taking into account clinical subtypes (restrictive--ANR--and bingeing/purging--ANB--subtypes). Family trios study of these 4 single nucleotide polymorphisms were performed in 114 probands with AN and both their parents recruited in two specialized French centres. A transmission disequilibrium was observed for the Leu72Met SNP of the preproghrelin gene and for the Ala67Thr SNP of the AgRP gene. When stratified by clinical subtype, these two polymorphisms were preferentially transmitted for the trios with a bingeing/purging proband. An excess of transmission of the Gln90Leu72 preproghrelin/obestatin haplotype in patients with AN was observed. These results do not provide evidence for a preferential transmission of the 66Met allele of BDNF but support the hypothesis that ghrelin and AGRP polymorphisms confers susceptibility to AN. Further simultaneous analysis of genetic variants of the biological determinants of energy metabolism and feeding behaviour in very large populations should contribute to the understanding of the high degree of heritability of eating disorders and to the description of pathophysiological patterns leading to life-threatening conditions in a highly redundant system.

Superoxide dismutase, catalase, glutathione peroxidase and gluthatione S-transferases M1 and T1 gene polymorphisms in three Brazilian population groups.

Science.gov (United States)

de Oliveira Hiragi, Cássia; Miranda-Vilela, Ana Luisa; Rocha, Dulce Maria Sucena; de Oliveira, Silviene Fabiana; Hatagima, Ana; de Nazaré Klautau-Guimarães, Maria

2011-01-01

Antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX1) reduce the oxidation rates in the organism. Gluthatione S-transferases (GSTs) play a vital role in phase 2 of biotransformation of many substances. Variation in the expression of these enzymes suggests individual differences for the degree of antioxidant protection and geographical differences in the distribution of these variants. We described the distribution frequency of CAT (21A/T), SOD2 (Ala9Val), GPX1 (Pro198Leu), GSTM1 and GSTT1 polymorphisms in three Brazilian population groups: Kayabi Amerindians (n = 60), Kalunga Afro-descendants (n = 72), and an urban mixed population from Federal District (n = 162). Frequencies of the variants observed in Kalunga (18% to 58%) and Federal District (33% to 63%) were similar to those observed in Euro and Afro-descendants, while in Kayabi (3% to 68%), depending on the marker, frequencies were similar to the ones found in different ethnic groups. Except for SOD2 in all population groups studied here, and for GPX1 in Kalunga, the genotypic distributions were in accordance with Hardy-Weinberg Equilibrium. These data can clarify the contribution of different ethnicities in the formation of mixed populations, such as that of Brazil. Moreover, outcomes will be valuable resources for future functional studies and for genetic studies in specific populations. If these studies are designed to comprehensively explore the role of these genetic polymorphisms in the etiology of human diseases they may help to prevent inconsistent genotype-phenotype associations in pharmacogenetic studies.

Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro)

DEFF Research Database (Denmark)

Yuca, Sevil Ari; Rendtorff, Nanna Dahl; Boulahbel, Houda

2012-01-01

Wolfram syndrome, also named "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an inherited association of juvenile-onset diabetes mellitus and optic atrophy as key diagnostic criteria. Renal tract abnormalities and neurodegenerative disorder may occur in the third...... and fourth decade. The wolframin gene, WFS1, associated with this syndrome, is located on chromosome 4p16.1. Many mutations have been described since the identification of WFS1 as the cause of Wolfram syndrome. We identified a new homozygous WFS1 mutation (c.1532T>C; p.Leu511Pro) causing Wolfram syndrome...

Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms

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Joanna Balding

2004-01-01

Full Text Available THE mechanisms responsible for development of inflammatory bowel disease (IBD have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n=172 and healthy controls (n=389 for polymorphisms in genes encoding various cytokines (interleukin (IL-1β, IL-6, tumour necrosis factor (TNF, IL-10, IL-1 receptor antagonist. Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-α-308 polymorphism (p=0.0135. There was also variation in the frequency of IL-6-174 and TNF-α-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p=0.01. We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear.

The Association of Polymorphisms in Leptin/Leptin Receptor Genes and Ghrelin/Ghrelin Receptor Genes With Overweight/Obesity and the Related Metabolic Disturbances: A Review.

Science.gov (United States)

Ghalandari, Hamid; Hosseini-Esfahani, Firoozeh; Mirmiran, Parvin

2015-07-01

Leptin and ghrelin are two important appetite and energy balance-regulating peptides. Common polymorphisms in the genes coding these peptides and their related receptors are shown to be associated with body weight, different markers of obesity and metabolic abnormalities. This review article aims to investigate the association of common polymorphisms of these genes with overweight/obesity and the metabolic disturbances related to it. The keywords leptin, ghrelin, polymorphism, single-nucleotide polymorphism (SNP), obesity, overweight, Body Mass Index, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (MeSH headings) were used to search in the following databases: Pubmed, Sciencedirect (Elsevier), and Google scholar. Overall, 24 case-control studies, relevant to our topic, met the criteria and were included in the review. The most prevalent leptin/leptin receptor genes (LEP/LEPR) and ghrelin/ghrelin receptor genes (GHRL/GHSR) single nucleotide polymorphisms studied were LEP G-2548A, LEPR Q223R, and Leu72Met, respectively. Nine studies of the 17 studies on LEP/LEPR, and three studies of the seven studies on GHRL/GHSR showed significant relationships. In general, our study suggests that the association between LEP/LEPR and GHRL/GHSR with overweight/obesity and the related metabolic disturbances is inconclusive. These results may be due to unidentified gene-environment interactions. More investigations are needed to further clarify this association.

THE ASSOCIATION OF GENE POLYMORPHISMS WITH ATHLETE STATUS IN UKRAINIANS

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Svitlana B. Drozdovska

2013-06-01

Full Text Available Athletic performance is a polygenic trait influenced by both environmental and genetic factors. Objective: to investigate individually and in combination the association of common gene polymorphisms with athlete status in Ukrainians. Methods: A total of 210 elite Ukrainian athletes (100 endurance-oriented and 110 power-orientated athletes and 326 controls were genotyped for ACE I/D, HIF1A Pro582Ser, NOS3 –786 T/C, PPARA intron 7 G/C, PPARG Pro12Ala and PPARGC1B Ala203Pro gene polymorphisms, most of which were previously reported to be associated with athlete status or related intermediate phenotypes in different populations. Results: Power-oriented athletes exhibited an increased frequency of the HIF1A Ser (16.1 vs. 9.420P = 0.034 and NOS3 T alleles (78.3 vs. 66.220P = 0.0019 in comparison with controls. Additionally, we found that the frequency of the PPARG Ala allele was significantly higher in power-oriented athletes compared with the endurance-oriented athletes (24.7 vs. 13.520P = 0.0076. Next, we determined the total genotype score (TGS, from the accumulated combination of the three polymorphisms, with a maximum value of 100 for the theoretically optimal polygenic score in athletes and controls. The mean TGS was significantly higher in power-oriented athletes (39.1 ± 2.3 vs. 32.6 ± 1.5; P = 0.0142 than in controls. Conclusions: We found that the HIF1A Ser, NOS3 T and PPARG Ala alleles were associated with power athlete status in Ukrainians.

Arg25Pro polymorphism of transforming growth factor-beta1 and its role in the pathogenesis of essential hypertension in Russian population of the Central Chernozem Region.

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Ivanov, V P; Solodilova, M A; Polonnikov, A V; Belugin, D A; Shestakov, A M; Ushachev, D V; Khoroshaya, I V; Katargina, L N; Kozhukhov, M A; Kolesnikova, O E

2007-07-01

We studied the relationship between Arg25Pro polymorphism of TGFbeta1 gene and predisposition to essential hypertension in the Russian population of Central Chernozem Region (n=402). An association was found between 25Pro allele and 25ArgPro genotype with low risk of essential hypertension in male individuals.

Platelet HPA-1 a/HPA-1 b polymorphism and the risk of periprocedural myocardial infarction in patients undergoing elective PCI

NARCIS (Netherlands)

Verdoia, M.; Secco, G.G.; Barbieri, L.; Cassetti, E.; Schaffer, A.; Sinigaglia, F.; Marino, P.; Suryapranata, H.; Luca, G. De

2014-01-01

Periprocedural myocardial infarction (PMI) represents a relatively common complication of percutaneous coronary intervention (PCI) and large interests have been focused on platelets in order to prevent such a complication. The single nucleotide polymorphism Leu33Pro of platelet glycoprotein IIIa has

Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

International Nuclear Information System (INIS)

Conde, João; Silva, Susana N; Azevedo, Ana P; Teixeira, Valdemar; Pina, Julieta Esperança; Rueff, José; Gaspar, Jorge F

2009-01-01

MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls) to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH). Using unconditional logistic regression we found that MLH3 (L844P, G>A) polymorphism GA (Leu/Pro) and AA (Pro/Pro) genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95) (p = 0.03) and OR = 0.62 (0.41-0.94) (p = 0.03), respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83), p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49), p = 0.01], GG/AA [OR = 2.11 (1.12-3,98), p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15), p = 0.02] all associated with an increased risk for breast cancer. It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results

Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

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Pina Julieta

2009-09-01

Full Text Available Abstract Background MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. Methods We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH. Results Using unconditional logistic regression we found that MLH3 (L844P, G>A polymorphism GA (Leu/Pro and AA (Pro/Pro genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95 (p = 0.03 and OR = 0.62 (0.41-0.94 (p = 0.03, respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83, p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49, p = 0.01], GG/AA [OR = 2.11 (1.12-3,98, p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15, p = 0.02] all associated with an increased risk for breast cancer. Conclusion It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results.

Ghrelin precursor gene polymorphism and methamphetamine dependence in the Korean population.

Science.gov (United States)

Yoon, Su-Jung; Pae, Chi-Un; Lee, Heejin; Choi, Bomoon; Kim, Tae-Suk; Lyoo, In Kyoon; Kwon, Do-Hoon; Kim, Dai-Jin

2005-12-01

Ghrelin is a recently isolated brain-gut peptide that has growth hormone-releasing and appetite-inducing activities. Several recent studies have suggested that ghrelin plays a major role in the pathophysiology of drug-seeking behavior and anxiety. Therefore, we assessed the effect of the ghrelin precursor polymorphism on methamphetamine dependence in the Korean population. One hundred and eighteen patients with methamphetamine dependence, according to the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria, and the 144 healthy controls were enrolled in this study. Genotyping for the ghrelin precursor polymorphism was performed by the polymerase chain reaction-restriction fragment length polymorphism-based technique. The genotypic and allelic distributions of the ghrelin precursor polymorphism in the patients with methamphetamine dependence were not significantly different from those of the control subjects. However, the Met72 carriers were associated with the emotional problems of methamphetamine dependence. The patients with the Met72 allele were more depressed and anxious than the homozygous patients with the wild Leu72 allele. The present study suggests that the ghrelin precursor polymorphism may not confer a susceptibility to the development of methamphetamine dependence in the Korean population. However, the Leu72Met polymorphism could have a potential role in the emotional problems that are associated with this disease.

Interleukin-6 and tumor necrosis factor-alpha gene polymorphisms in chronic idiopathic urticaria.

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Tavakol, M; Amirzargar, A A; Movahedi, M; Aryan, Z; Bidoki, A Z; Gharagozlou, M; Aghamohammadi, A; Nabavi, M; Ahmadvand, A; Behniafard, N; Heidari, K; Soltani, S; Rezaei, N

2014-01-01

This study was performed to evaluate association of gene polymorphisms among proinflammatory cytokines and susceptibility to chronic idiopathic urticaria (CIU). Ninety patients with prolonged urticaria more than 6 weeks were included as case group. Single nucleotide polymorphisms (SNPs) of IL-6 (G/C -174, G/A nt565) and TNF-α (G/A -308, G/A -238) were evaluated, using polymerase chain reaction (PCR); and the results were compared to the control group. G allele was significantly higher in the patients at locus of -238 of promoter of TNF-α gene (p<0.001). Frequency of following genotypes were significantly lower in patients with CIU, compared to controls: AG at -308 and GA at -238 of TNF-α gene (p<0.05 and p<0.001, respectively), CG at -174 and GG at +565 of IL-6 gene (p<0.05). Additionally, following genotypes were more common among patients with CIU: GG at -308 and -238 of TNF-α gene (p<0.05 and p<0.001, respectively), GG at -174 and GA at +565 of IL-6 gene (p<0.05). Pro-inflammatory cytokine gene polymorphisms can affect susceptibility to CIU. TNF-α promoter polymorphisms as well as IL-6 gene polymorphisms are associated with CIU. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

Association of Gene Polymorphisms in Interleukin 6 in Infantile Bronchial Asthma.

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Babusikova, Eva; Jurecekova, Jana; Jesenak, Milos; Evinova, Andrea

2017-07-01

The genetic background of bronchial asthma is complex, and it is likely that multiple genes contribute to its development both directly and through gene-gene interactions. Cytokines contribute to different aspects of asthma, as they determine the type, severity and outcomes of asthma pathogenesis. Allergic asthmatics undergoing an asthmatic attack exhibit significantly higher levels of pro-inflammatory cytokines, such as interleukins and chemokines. In recent years, cytokines and their receptors have been shown to be highly polymorphic, and this prompted us to investigate interleukin 6 promoter polymorphisms at position -174G/C (rs1800795) and at -572G/C (rs1800796) in relation to asthma in children. Interleukin 6 promoter polymorphisms were analyzed in bronchial asthma patients and healthy children using polymerase chain reaction-restriction fragment length polymorphism analysis. We observed a significant association between polymorphism at -174G/C and bronchial asthma (OR=3.4, 95% CI: 2.045-5.638, P<.001). Higher associations between polymorphism at IL-6 -174G/C and bronchial asthma were observed in atopic patients (OR=4.1, 95% CI: 2.308-7.280, P<8.10 -7 ). Interleukin 6 polymorphism is associated with bronchial asthma, particularly its atopic phenotype. Expression and secretion of interleukins in asthmatic patients may be affected by genetic polymorphisms, and could have a disease-modifying effect in the asthmatic airway and modify the therapeutic response. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Human Retrotransposon Insertion Polymorphisms Are Associated with Health and Disease via Gene Regulatory Phenotypes

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Lu Wang

2017-08-01

Full Text Available The human genome hosts several active families of transposable elements (TEs, including the Alu, LINE-1, and SVA retrotransposons that are mobilized via reverse transcription of RNA intermediates. We evaluated how insertion polymorphisms generated by human retrotransposon activity may be related to common health and disease phenotypes that have been previously interrogated through genome-wide association studies (GWAS. To address this question, we performed a genome-wide screen for retrotransposon polymorphism disease associations that are linked to TE induced gene regulatory changes. Our screen first identified polymorphic retrotransposon insertions found in linkage disequilibrium (LD with single nucleotide polymorphisms that were previously associated with common complex diseases by GWAS. We further narrowed this set of candidate disease associated retrotransposon polymorphisms by identifying insertions that are located within tissue-specific enhancer elements. We then performed expression quantitative trait loci analysis on the remaining set of candidates in order to identify polymorphic retrotransposon insertions that are associated with gene expression changes in B-cells of the human immune system. This progressive and stringent screen yielded a list of six retrotransposon insertions as the strongest candidates for TE polymorphisms that lead to disease via enhancer-mediated changes in gene regulation. For example, we found an SVA insertion within a cell-type specific enhancer located in the second intron of the B4GALT1 gene. B4GALT1 encodes a glycosyltransferase that functions in the glycosylation of the Immunoglobulin G (IgG antibody in such a way as to convert its activity from pro- to anti-inflammatory. The disruption of the B4GALT1 enhancer by the SVA insertion is associated with down-regulation of the gene in B-cells, which would serve to keep the IgG molecule in a pro-inflammatory state. Consistent with this idea, the B4GALT1 enhancer

Development of a chromosomally integrated metabolite-inducible Leu3p-alpha-IPM "off-on" gene switch.

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Maria Poulou

2010-08-01

Full Text Available Present technology uses mostly chimeric proteins as regulators and hormones or antibiotics as signals to induce spatial and temporal gene expression.Here, we show that a chromosomally integrated yeast 'Leu3p-alpha-IotaRhoMu' system constitutes a ligand-inducible regulatory "off-on" genetic switch with an extensively dynamic action area. We find that Leu3p acts as an active transcriptional repressor in the absence and as an activator in the presence of alpha-isopropylmalate (alpha-IotaRhoMu in primary fibroblasts isolated from double transgenic mouse embryos bearing ubiquitously expressing Leu3p and a Leu3p regulated GFP reporter. In the absence of the branched amino acid biosynthetic pathway in animals, metabolically stable alpha-IPM presents an EC(50 equal to 0.8837 mM and fast "OFF-ON" kinetics (t(50ON = 43 min, t(50OFF = 2.18 h, it enters the cells via passive diffusion, while it is non-toxic to mammalian cells and to fertilized mouse eggs cultured ex vivo.Our results demonstrate that the 'Leu3p-alpha-IotaRhoMu' constitutes a simpler and safer system for inducible gene expression in biomedical applications.

Photoreceptor Differentiation following Transplantation of Allogeneic Retinal Progenitor Cells to the Dystrophic Rhodopsin Pro347Leu Transgenic Pig

DEFF Research Database (Denmark)

Klassen, H; Kiilgaard, Jens Folke; Warfvinge, K

2012-01-01

Purpose. Transplantation of stem, progenitor, or precursor cells has resulted in photoreceptor replacement and evidence of functional efficacy in rodent models of retinal degeneration. Ongoing work has been directed toward the replication of these results in a large animal model, namely, the pig....... Methods. Retinal progenitor cells were derived from the neural retina of GFP-transgenic pigs and transplanted to the subretinal space of rhodopsin Pro347Leu-transgenic allorecipients, in the early stage of the degeneration and the absence of immune suppression. Results. Results confirm the survival...

Cross-resistance patterns to acetolactate synthase (ALS)-inhibiting herbicides of flixweed (Descurainia sophia L.) conferred by different combinations of ALS isozymes with a Pro-197-Thr mutation or a novel Trp-574-Leu mutation.

Science.gov (United States)

Deng, Wei; Yang, Qian; Zhang, Yongzhi; Jiao, Hongtao; Mei, Yu; Li, Xuefeng; Zheng, Mingqi

2017-03-01

Acetolactate synthase (ALS) is the common target of ALS-inhibiting herbicides, and target-site ALS mutations are the main mechanism of resistance to ALS-inhibiting herbicides. In this study, ALS1 and ALS2 genes with full lengths of 2004bp and 1998bp respectively were cloned in individual plants of susceptible (S) or resistant (R) flixweed (Descurainia sophia L.) populations. Two ALS mutations of Pro-197-Thr and/or Trp-574-Leu were identified in plants of three R biotypes (HB24, HB30 and HB42). In order to investigate the function of ALS isozymes in ALS-inhibiting herbicide resistance, pHB24 (a Pro-197-Thr mutation in ALS1 and a wild type ALS2), pHB42 (a Trp-574-Leu mutation in ALS1 and a wild type ALS2) and pHB30 (a Trp-574-Leu mutation in ALS1 and a Pro-197-Thr mutation in ALS2) subpopulations individually homozygous for different ALS mutations were generated. Individuals of pHB30 had mutations in each isozyme of ALS and had higher resistance than pHB24 and pHB42 populations containing mutations in only one ALS isozyme. Moreover, the pHB24 had resistance to SU, TP and SCT herbicides, whereas pHB24 and pHB42 had resistance to these classes of herbicides as well as IMI and PTB herbicides. The sensitivity of isolated ALS enzyme to inhibition by herbicides in these populations correlated with whole plant resistance levels. Therefore, reduced ALS sensitivity resulting from the mutations in ALS was responsible for resistance to ALS-inhibiting herbicides in flixweed. Copyright © 2016 Elsevier Inc. All rights reserved.

Energy balance and food intake: the role of PPARgamma gene polymorphisms.

Science.gov (United States)

Cecil, Joanne E; Watt, Peter; Palmer, Colin N; Hetherington, Marion

2006-06-30

Mechanisms regulating energy balance involve complex interactions between genetic, environmental and behavioural (learnt and intrinsic) factors. Genotype may drive the partitioning of energy metabolism and predispose to site-specific adiposity, culminating in a state of energy imbalance. One candidate gene with a direct link to adiposity is the peroxisome proliferator-activated receptor gamma (PPARG) gene. PPARG is a cell nuclear receptor expressed almost exclusively in adipose tissue that regulates adipocyte differentiation, lipid metabolism and insulin sensitivity. PPARgamma appears to be a key regulator of energy balance, with polymorphisms on the PPARG gene linked to obesity and effects on body composition. Our research has confirmed an association between the pro12ala allele and reduced incidence of obesity in pre-pubertal children and there are strong associations between genetic variation at the PPARG locus and percentage body fat. Moreover, our evidence suggests that PPARG C-681G and pro12ala polymorphisms display opposing effects in terms of growth phenotype, with pro12Ala associated with deficient energy utilisation, leading to reduced growth and the G-681 variant associated with accelerated growth compared with wildtypes. Common differences in this gene have also been associated with variations in body weight in response to dietary macronutrients. Preliminary evidence suggests that PPARG variants may even be involved in the control of short term energy compensation. Taken together these data suggest that the role of PPARG is varied and complex, influencing fat deposition and growth velocity early in life, with potential impact in the control of energy intake and appetite regulation, and could provide a key target for future research and anti-obesity agents.

Preliminary LEU fuel cycle analyses for the Belgian BR2 reactor

International Nuclear Information System (INIS)

Deen, J.R.; Snelgrove, J.L.

1986-01-01

Fuel cycle calculations have been performed with reference HEU fuel and LEU fuel using Cd wires or boron as burnable absorbers. The 235 U content in the LEU element has increased 20% to 480g compared to the reference HEU element. The number of fuel plates has remained unchanged while the fuel meat thickness has increased to 0.76 mm from 0.51 mm. The LEU meat density is 5.1 Mg U/m 3 . The reference fuel cycle was a 31 element core operating at 56 MW with a 19.8 day cycle length and eight fresh elements loaded per cycle. Comparable fuel cycle characteristics can be achieved using the proposed LEU fuel element with either Cd wires or boron burnable absorbers. The neutron flux for E/sub n/ > 1 eV changes very little (<5%) in LEU relative to HEU cores. Thermal flux reductions are 5 to 10% in non-fueled positions, and 20 to 30% in fuel elements

Association of ghrelin polymorphisms with metabolic syndrome in Han Nationality Chinese.

Science.gov (United States)

Xu, Ling-Ling; Xiang, Hong-Ding; Qiu, Chang-Chun; Xu, Qun

2008-06-01

To investigate the association of ghrelin gene polymorphisms with metabolic syndrome in Han Nationality Chinese. A total of 240 patients with metabolic syndrome and 427 adults aged above forty years were recruited. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The allelic frequency of the Leu72Met polymorphism was 17.3% in the patient group and 11.9% in the control group (chi2 = 7.36, P = 0.007). Metabolic syndrome was more prevalent among carriers of the Met72 variant (43.8 vs 33.1%, age- and sex-adjusted odds ratio = 1.57, P = 0.01). No Arg51Gln variants were found in our study subjects. Rather than being associated with its individual components, Leu72Met polymorphism is associated with metabolic syndrome in the Han Nationality Chinese. Arg51Gln polymorphism is rare in the Han Nationality Chinese.

Polymorphisms in the B-type natriuretic peptide (BNP) gene are associated with NT-proBNP levels but not with diabetic nephropathy or mortality in type 1 diabetic patients

DEFF Research Database (Denmark)

Lajer, Maria Stenkil; Tarnow, Lise; Jorsal, Anders

2007-01-01

BACKGROUND: Circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with diabetic nephropathy and independently predict excess cardiovascular morbidity and mortality. Therefore, we investigated the association between two polymorphisms -381T/C and 1551G....../A of the BNP gene, plasma NT-proBNP levels and mortality prognosis in 380 type 1 diabetic patients with and without diabetic nephropathy. METHODS: In a prospective observational follow-up study, 197 type 1 diabetic patients with diabetic nephropathy {121 men, age [mean (SD)] 41 +/- 9.5 years, duration...... of diabetes 28 +/- 8.0 years, glomerular filtration rate 67 +/- 28 ml/min/1.73 m2}, and a matched control group of 183 patients with longstanding type 1 diabetes and persistent normoalbuminuria (111 men, age 43 +/- 10.0 years, duration of diabetes 27 +/- 8.3 years) were followed for 12.6 (0.0-12.9) years...

Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women.

Science.gov (United States)

Saliba, Louise F; Reis, Rodrigo S; Brownson, Ross C; Hino, Adriano A; Tureck, Luciane V; Valko, Cheryl; de Souza, Ricardo L R; Furtado-Alle, Lupe

2014-03-01

The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713), ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (2 × 2) were used to analyze the intervention effect between polymorphisms and BMI over the period and after stratification for age and socioeconomic status (SES). The weight loss intervention resulted in decreased BMI over the seven-week period (p polymorphism carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms did not moderate weight loss, the Gln27Glu polymorphism carriers showed a lower BMI compared to non-carriers in the low SES (p = 0.018) and the 30-39 y (p = 0.036) groups, suggesting a role for this polymorphism related to BMI control.

The association between the Pro12Ala polymorphism in the PPARg gene and

DEFF Research Database (Denmark)

Schow, Trine

2006-01-01

The interaction between the Pro12Ala polymorphism in peroxisome-proliferator-activator receptor gamma PPARg -2 and physical activity in the association with obesity (BMI ≥30 kg m-2) was explored in 901 women and 903 men between 30 and 75 years participating in a population survey of cardiovascular...... disease risk factors in Vara, Sweden, (participation rate 81%). Questionnaires and interviews covered physical activity at leisure time (LTPA), smoking habits and socio-economic background, and anthropometric measures were ascertained. Obesity was found in 26% of the women and 20% of the men......: 0.19-5.91). This association was not seen in men or in women women above 50 years, but this risk was prevented already by a moderate level of LTPA. These findings support the emphasis...

PlA polymorphism and platelet reactivity following clopidogrel loading dose in patients undergoing coronary stent implantation.

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Angiolillo, Dominick J; Fernandez-Ortiz, Antonio; Bernardo, Esther; Alfonso, Fernando; Sabaté, Manel; Fernández, Cristina; Stranieri, Chiara; Trabetti, Elisabetta; Pignatti, Pier Franco; Macaya, Carlos

2004-01-01

The PlA polymorphism (Leu33Pro) of the platelet glycoprotein (GP) IIIa gene has been suggested to play an important role in coronary thrombosis. In vitro studies have shown differences for this polymorphism in platelet sensitivity towards antiplatelet drugs (aspirin and abciximab), suggesting a pharmacogenetic modulation. The aim of the study was to assess the modulatory effect of the PlA polymorphism on clopidogrel-induced antiplatelet effects in 38 patients undergoing coronary stent implantation receiving a 300 mg clopidogrel loading-dose. Platelet reactivity was assessed as GPIIb/IIIa activation and P-selectin expression in platelets stimulated with 2 micromol/l adenosine diphosphate using whole blood flow cytometry. The distribution of the homozygous PlA1/A1 and heterozygous PlA1/A2 genotypes were 74 and 26%, respectively. PlA2 carriers had a higher degree of GPIIb/IIIa activation (P = 0.05) and P-selectin expression (P = 0.02) during the overall study time course and a lower antiplatelet effect to a 300 mg clopidogrel loading-dose up to 24 h following intervention (P < 0.05). In conclusion, the Pl polymorphism of the GPIIIa gene modulates platelet reactivity towards clopidogrel front loading in patients undergoing coronary stenting. This suggests the need for individualized antithrombotic regimens to optimally inhibit platelet reactivity. Copyright 2004 Lippincott Williams and Wilkins

Associations of MYF5 gene polymorphisms with meat quality traits in different domestic pig (Sus scrofa populations

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Min Liu

2007-03-01

Full Text Available The MYF5 gene is first inducibly expressed in muscle cell during embryonic muscle development and plays an important role in regulating the differentiation of skeletal muscle precursors. In this study we used PCR-RFLP to investigate two pig (Sus scrofa populations (n = 302 for two MYF5 gene polymorphisms, a previously unreported novel Met-Leu shift single nucleotide polymorphism (SNP MYF5/Hsp92II located on exon 1 and the previously identified intron 1 MYF5/HinfI SNP. Haplotype and association analysis showed that haplotypes of the two SNPs were significantly associated with drip loss rate (DLR, p < 0.05, water holding capacity (WHC, p < 0.05, biceps femoris meat color value (MCV2, p < 0.05, biceps femoris marbling score (MM2, p < 0.01, longissimus dorsi intramuscular fat percentage (IMF, p < 0.01 and longissimus dorsi Water moisture content (WM, p < 0.01 in the population 2. However, further studies are needed to confirm these preliminary results.

The Gain-of-Function Integrin β3 Pro33 Variant Alters the Serotonin System in the Mouse Brain.

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Dohn, Michael R; Kooker, Christopher G; Bastarache, Lisa; Jessen, Tammy; Rinaldi, Capria; Varney, Seth; Mazalouskas, Matthew D; Pan, Hope; Oliver, Kendra H; Velez Edwards, Digna R; Sutcliffe, James S; Denny, Joshua C; Carneiro, Ana M D

2017-11-15

Engagement of integrins by the extracellular matrix initiates signaling cascades that drive a variety of cellular functions, including neuronal migration and axonal pathfinding in the brain. Multiple lines of evidence link the ITGB3 gene encoding the integrin β3 subunit with the serotonin (5-HT) system, likely via its modulation of the 5-HT transporter (SERT). The ITGB3 coding polymorphism Leu33Pro (rs5918, Pl A2 ) produces hyperactive αvβ3 receptors that influence whole-blood 5-HT levels and may influence the risk for autism spectrum disorder (ASD). Using a phenome-wide scan of psychiatric diagnoses, we found significant, male-specific associations between the Pro33 allele and attention-deficit hyperactivity disorder and ASDs. Here, we used knock-in (KI) mice expressing an Itgb3 variant that phenocopies the human Pro33 variant to elucidate the consequences of constitutively enhanced αvβ3 signaling to the 5-HT system in the brain. KI mice displayed deficits in multiple behaviors, including anxiety, repetitive, and social behaviors. Anatomical studies revealed a significant decrease in 5-HT synapses in the midbrain, accompanied by decreases in SERT activity and reduced localization of SERTs to integrin adhesion complexes in synapses of KI mice. Inhibition of focal adhesion kinase (FAK) rescued SERT function in synapses of KI mice, demonstrating that constitutive active FAK signaling downstream of the Pro32Pro33 integrin αvβ3 suppresses SERT activity. Our studies identify a complex regulation of 5-HT homeostasis and behaviors by integrin αvβ3, revealing an important role for integrins in modulating risk for neuropsychiatric disorders. SIGNIFICANCE STATEMENT The integrin β3 Leu33Pro coding polymorphism has been associated with autism spectrum disorders (ASDs) within a subgroup of patients with elevated blood 5-HT levels, linking integrin β3, 5-HT, and ASD risk. We capitalized on these interactions to demonstrate that the Pro33 coding variation in the murine

Impact of the Pro12Ala Polymorphism of the PPAR-Gamma 2 Gene on Metabolic and Clinical Characteristics in the Palestinian Type 2 Diabetic Patients

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S. Ereqat

2009-01-01

Full Text Available Peroxisome proliferators activated receptor-gamma2 (PPARγ2 represents the transcriptional master regulator of adipocyte differentiation and therefore has been suggested as a candidate gene for obesity, insulin resistance, and dyslipidemia. The objective of the study was to investigate for the first time the potential association of the most common variant Pro12Ala (p.P12A substitution of the PPARγ2 gene with body mass index (BMI, blood pressure, fasting plasma glucose, plasma total cholesterol, LDL and HDL cholesterol, and plasma triglyceride in a sample of 202 (138 females and 64 male type 2 diabetic Palestinians. Genotyping of the PPARγ2 p.P12A polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis. The A12 allele was associated with lower fasting plasma glucose (P=.03 but had no influence on blood pressure, BMI, or other metabolic parameters. In obese patients, the p.P12A substitution was associated with elevated total plasma cholesterol levels (P=.02 and a tendency toward increased LDL cholesterol level (P=.06. In conclusion, the p.P12A variant of the PPARγ2 may influence cardiovascular risk through effects on lipid metabolism in obese T2D Palestinian patients.

Recombinant Brucella abortus gene expressing immunogenic protein

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Mayfield, J.E.; Tabatabai, L.B.

1991-06-11

This patent describes a synthetic recombinant DNA molecule containing a DNA sequence. It comprises a gene of Brucella abortus encoding an immunogenic protein having a molecular weight of approximately 31,000 daltons as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis under denaturing conditions, the protein having an isoelectric point around 4.9, and containing a twenty-five amino acid sequence from its amino terminal end consisting of Gln-Ala-Pro-Thr-Phe-Phe-Arg-Ile-Gly-Thr-Gly-Gly-Thr-Ala-Gly-Thr-Tyr-Tyr-Pro-Ile-Gly-Gly-Leu-Ile-Ala, wherein Gln, Ala, Pro, Thr, Phe, Arg, Ile, Gly, Tyr, and Leu, respectively, represent glutamine, alanine, proline, threonine, phenylalanine, arginine, isolecuine, glycine, tyrosine, and leucine.

Polymorphisms in the selenoprotein S gene: lack of association with autoimmune inflammatory diseases

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Díaz-Rubio Manuel

2008-07-01

Full Text Available Abstract Background Selenoprotein S (SelS protects the functional integrity of the endoplasmic reticulum against the deleterious effects of metabolic stress. SEPS1/SelS polymorphisms have been involved in the increased release of pro-inflammatory cytokines interleukin (IL-1β, tumor necrosis factor (TNF-α and IL-6 in macrophages. We aimed at investigating the role of the SEPS1 variants previously associated with higher plasma levels of these cytokines and of the SEPS1 haplotypes in the susceptibility to develop immune-mediated diseases characterized by an inflammatory component. Results Six polymorphisms distributed through the SEPS1 gene (rs11327127, rs28665122, rs4965814, rs12917258, rs4965373 and rs2101171 were genotyped in more than two thousand patients suffering from type 1 diabetes, rheumatoid arthritis or inflammatory bowel diseases and 550 healthy controls included in the case-control study. Conclusion Lack of association of SEPS1 polymorphisms or haplotypes precludes a major role of this gene increasing predisposition to these inflammatory diseases.

The association of ghrelin polymorphisms with coronary artery disease and ischemic chronic heart failure in an elderly Chinese population.

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Zhang, Qin; Huang, Wei-Dong; Lv, Xue-Ying; Yang, Yun-Mei

2011-04-01

To investigate the association of coronary artery disease (CAD) and ischemic heart failure (IHF) with polymorphisms of the ghrelin gene in elderly Chinese patients. Fifty-six patients with ischemic heart failure, sixty patients with coronary artery disease without heart failure, and one hundred healthy control subjects participated in the study. The polymorphisms were evaluated by polymerase chain reaction, sequencing, and fragment length polymorphism analysis. Only one single nucleotide polymorphism (SNP), Leu72Met (408C/A), was observed across all samples. Gene frequencies of CC and allele frequencies of C were significantly greater in the CAD with IHF group than those in the CAD without IHF group (p=0.025, p=0.011). There was no significant association between the Leu72Met SNP with coronary artery disease risk factors. Our results suggest that a C allele at position 408 of the ghrelin gene is associated with genetic susceptibility to ischemic heart failure in Chinese elders. Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

R497K polymorphism in epidermal growth factor receptor gene is associated with the risk of acute coronary syndrome

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Pan Xin-Min

2008-07-01

Full Text Available Abstract Background Previous studies suggested that genetic polymorphisms in the epidermal growth factor receptor (EGFR gene had been implicated in the susceptibility to some tumors and inflammatory diseases. EGFR has been recently implicated in vascular pathophysiological processes associated with excessive remodeling and atherosclerosis. Acute coronary syndrome (ACS is a clinical manifestation of preceding atherosclerosis. Our purpose was to investigate the association of the EGFR polymorphism with the risk of ACS. In this context, we analyzed the HER-1 R497K and EGFR intron 1 (CAn repeat polymorphisms in 191 patients with ACS and 210 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP strategy and direct sequencing. Results There were significant differences in the genotype and allele distribution of R497K polymorphism of the EGFR gene between cases and controls. The Lys allele had a significantly increased risk of ACS compared with the Arg allele (adjusted OR = 1.49, 95% CI: 1.12–1.98, adjusted P = 0.006. However, no significant relationship between the number of (CAn repeats of EGFR intron 1 (both alleles P = 0.911. Considering these two polymorphisms together, there was no statistically significant difference between the two groups. Conclusion R497K polymorphism of the EGFR gene is significantly associated with the risk of ACS. Our data suggests that R497K polymorphism may be used as a genetic susceptibility marker of the ACS.

Implication of the Pro12Ala polymorphism of the PPAR-gamma 2 gene in type 2 diabetes and obesity in the French population

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Charles Marie-Aline

2005-03-01

Full Text Available Abstract Background The Pro12Ala Single Nucleotide Polymorphism (SNP of the Peroxisome Proliferator-Activated Receptor gamma 2 (PPAR-gamma 2 has been associated with insulin resistance and type 2 diabetes (T2D and also inconsistently with obesity. The aim of this study was to evaluate the impact of this SNP with regards to T2D and childhood and adult obesity in the French Caucasian population. Methods We conducted three independent case/control studies encompassing 2126 cases and 1124 controls. Results We found a significant association between PPAR-gamma 2 Pro12Ala SNP and T2D (p = 0.04, OR = 1.37, which was stronger when the T2D cohort was stratified according to the obesity status (p = 0.03, OR = 1.81 in obese T2D subjects. In contrast, there was no association between the Pro12Ala SNP and childhood and adulthood obesity. In normal glucose tolerant obese adults (but not in lean subjects, the Pro12 allele was associated with a significant increase in fasting insulin levels (p = 0.01, and in insulin resistance estimated by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR (p = 0.003, after adjustment for age, gender and BMI. We didn't detect evidence for an interaction effect between the Pro12Ala SNP and the obesity status with respect to the HOMA-IR index in normal glucose tolerant children, but we found a borderline interaction (p = 0.06 in normal glucose tolerant adults. Conclusion Our results showed that the Pro12Ala polymorphism is not associated with childhood or adult obesity in the French Caucasian population. In contrast, we confirm a contribution of the PPAR-gamma 2 Pro12 allele in the genetic risk forT2D, especially in obese subjects, where this allele worsens insulin resistanceand increases fasting insulin levels.

Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women

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Louise F. Saliba

2014-01-01

Full Text Available The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713, ADRB3 (Trp64Arg, rs4994 and GHRL (Leu72Met, rs696217 polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109. The body mass index (BMI was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (2 x 2 were used to analyze the intervention effect between polymorphisms and BMI over the period and after stratification for age and socioeconomic status (SES. The weight loss intervention resulted in decreased BMI over the seven-week period (p < 0.001, for high and low SES (p < 0.05 and mainly for participants with 30-49 y. The intervention did not result in a statistically significant difference in weight loss between polymorphism carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms did not moderate weight loss, the Gln27Glu polymorphism carriers showed a lower BMI compared to non-carriers in the low SES (p = 0.018 and the 30-39 y (p = 0.036 groups, suggesting a role for this polymorphism related to BMI control.

Do gene polymorphism in IL-1β, TNF-α and IL-6 influence therapeutic response in patients with drug refractory epilepsy?

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Tiwari, Prabhakar; Dwivedi, Rekha; Mansoori, Nasim; Alam, Rizwan; Chauhan, Ugam Kumari; Tripathi, Manjari; Mukhopadhyay, Asok Kumar

2012-09-01

Pro-inflammatory cytokines may play an important pathophysiological role in patients with epilepsy. To understand the role of genes encoding pro-inflammatory cytokines in epilepsy, this study aimed to evaluate the polymorphisms of the promoter regions of IL-1β-511C>T (rs16944), TNF-α-308G>A (rs1800629) and IL-6-174G>C (rs1800795) genes and to look into the interaction between these genes in influencing seizure susceptibility, seizure frequency and response to therapy. The comparative frequency of polymorphism was determined in rs16944, rs1800629 and rs1800795 using PCR-RFLP in a group of 120 persons with epilepsy (PWE) and 110 ethnically matched healthy subjects of comparable age and sex in the North Indian population. Alleles and genotypes of rs16944, rs1800629 and rs1800795 were not found to influence the odds ratio of having susceptibility to epilepsy. Also gene-gene interaction of possible nine combinations of these genes did not show any positive association with epilepsy. The genotype and allelic frequency of rs1800795 showed a significant association (prs16944 and rs1800629 were not found to have such effect. This study demonstrates that the rs16944, rs1800629 and rs1800795 polymorphism does not act as a strong susceptibility factor for epilepsy in North Indian population. The genotypic association of rs1800795 with seizure frequency and drug-refractory epilepsy raises the issue that a specific set of polymorphic genes can influence seizures and therapeutic response in epilepsy. Copyright © 2012 Elsevier B.V. All rights reserved.

Association of Pro12Ala polymorphism of PPAR-γ2 Gene and diabetic retinopathy in type 2 diabetes

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Yong-Qing Liu

2013-06-01

Full Text Available AIM: To observe the relationship between Prol2Ala polymorphism of peroxisome proliferator activated receptor-γ2(PPAR-γ2gene and diabetic retinopathy(DRwith type 2 diabetic mellitus(T2DMof the Han nationality in Shanxi province. METHODS: Totally 90 patients with T2DM were selected into our research, who were at the age of 40 to 70 years old, diabetic duration from 10 to 20 years, blood pressure PPAR-γ2 gene were determined by polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLPassay in all the patients. RESULTS: PCR results showed that there were 2 alleles and 3 genotypes in the groups. The frequency of genotype PP, PA, AA were 40.0%, 53.3%, 6.7% in NDR group, 70.0%, 30.0%, 0.0% in BDR group, 76.7%, 23.3%, 0% in PDR group, respectively. The allele frequency(χ2=10.208and gene frequency(χ2=10.351were statistically significant(PCONCLUSION: The alanine variant of Prol2Ala polymorphism of PPAR-γ2 gene is associated with DR in type 2 diabetes among the Hans in Shanxi area, and the Ala allele might be a protective factor for the development of diabetic retinopathy.

Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in Koreans.

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Choi, Hyung Jin; Cho, Young Min; Moon, Min Kyong; Choi, Hye Hun; Shin, Hyoung Doo; Jang, Hak Chul; Kim, Seong Yeon; Lee, Hong Kyu; Park, Kyong Soo

2006-11-01

Ghrelin is known to play a role in glucose metabolism and in beta-cell function. There are controversies regarding the role of ghrelin polymorphisms in diabetes and diabetes-related phenotypes. The objective of this study was to examine polymorphisms of the ghrelin gene in a Korean cohort and investigate associations between them and susceptibility to type 2 diabetes and its related phenotypes. The ghrelin gene was sequenced to identify polymorphisms in 24 DNA samples. Common variants were then genotyped in 760 type 2 diabetic patients and 641 nondiabetic subjects. Genetic associations with diabetes-related phenotypes were also analyzed. Nine polymorphisms were identified, and four common polymorphisms [g.-1500C>G, g.-1062G > C, g.-994C > T, g.+408C > A (Leu72Met)] were genotyped in a larger study. The genotype distributions of these four common polymorphisms in type 2 diabetes patients were similar to those of normal nondiabetic controls. However, these four common polymorphisms were variably associated with several diabetes-related phenotypes, such as high-density lipoprotein (HDL) cholesterol, fasting plasma glucose, and homeostasis model assessment of insulin resistance. In particular, subjects harboring g.-1062C were associated with a lower serum HDL cholesterol level after adjusting for other variables (P = 0.0004 or 0.01 after Bonferroni correction for 24 tests). The aforementioned four common polymorphisms in the ghrelin gene were not found to be significantly associated with susceptibility to type 2 diabetes mellitus in the Korean population. However, the common polymorphism g.-1062G > C in the promoter region of the ghrelin gene was found to be significantly associated with serum HDL cholesterol levels.

Compound heterozygous mutations (p.Leu13Pro and p.Tyr294*) associated with factor VII deficiency cause impaired secretion through ineffective translocation and extensive intracellular degradation of factor VII.

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Suzuki, Keijiro; Sugawara, Takeshi; Ishida, Yoji; Suwabe, Akira

2013-02-01

Congenital coagulation factor VII (FVII) deficiency is a rare coagulation disease. We investigated the molecular mechanisms of this FVII deficiency in a patient with compound heterozygous mutations. A 22-year-old Japanese female was diagnosed with asymptomatic FVII deficiency. The FVII activity and antigen were greatly reduced (activity, 13.0%; antigen, 10.8%). We analyzed the F7 gene of this patient and characterized mutant FVII proteins using in vitro expression studies. Sequence analysis revealed that the patient was compound heterozygous with a point mutation (p.Leu13Pro) in the central hydrophobic core of the signal peptides and a novel non-sense mutation (p.Tyr294*) in the catalytic domain. Expression studies revealed that mutant FVII with p.Leu13Pro (FVII13P) showed less accumulation in the cells (17.5%) and less secretion into the medium (64.8%) than wild type showed. Truncated FVII resulting from p.Tyr294* (FVII294X) was also decreased in the cells (32.0%), but was not secreted into the medium. Pulse-chase experiments revealed that both mutants were extensively degraded intracellularly compared to wild type. The majority of FVII13P cannot translocate into endoplasmic reticulum (ER). However, a small amount of FVII13P was processed normally with post-translational modifications and was secreted into the medium. The fact that FVII294X was observed only in ER suggests that it is retained in ER. Proteasome apparently plays a central role in these degradations. These findings demonstrate that both mutant FVIIs impaired secretion through ineffective translocation to and retention in ER with extensive intracellular degradation, resulting in an insufficient phenotype. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma-2 gene (PPARγ2 is associated with increased risk of coronary artery disease: a meta-analysis.

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Zhijun Wu

Full Text Available BACKGROUND: Contradictory results have been reported regarding the association between Pro12Ala polymorphism of PPARγ2 and coronary artery disease (CAD. We sought to estimate the inconsistent results by performing a comprehensive meta-analysis. METHODS: Studies in English or Chinese publications were identified by screening MEDLINE, Embase, CNKI, Wanfang and CBM. 22 studies including 8948 cases and 14427 controls were selected. A random-effects model was applied to combine the divergent outcomes of the individual studies, while addressing between-study heterogeneity and publication bias. RESULTS: The Pro12Ala polymorphism of control population followed Hardy-Weinberg equilibrium for all studies (P>0.05. Overall, a marginal increased risk of CAD under the recessive genetic model (AlaAla vs ProAla+ProPro: P = 0.04, OR = 1.31, 95%CI 1.01-1.69, P(heterogeneity = 0.67, I(2 = 0% and the homozygote comparison (AlaAla vs ProPro: P = 0.04,OR = 1.30, 95%CI 1.01-1.68, P(heterogeneity = 0.68, I(2 = 0% was observed. In the subgroup analysis by ethnicity, carriers of AlaAla homozygotes had a significant increased risk for CAD among Caucasians (AlaAla vs ProAla+ProPro: P = 0.01, OR = 1.45, 95%CI 1.08-1.96, P(heterogeneity = 0.48, I(2 = 0%; AlaAla vs ProPro: P = 0.02,OR = 1.44, 95%CI 1.07-1.93, P(heterogeneity = 0.46, I(2 = 0%. After dividing into population source, the CAD risk magnitude of hospital-based studies was distinctly strengthened under the recessive model (P = 0.03,OR = 1.85,95%CI 1.07-3.19, P(heterogeneity = 0.87,I(2 = 0% and the homozygote comparison (P = 0.03,OR = 1.83, 95%CI 1.06-3.16, P(heterogeneity = 0.88, I(2 = 0%. There was no observable publication bias as reflected by funnel plot and Egger's linear regression test (t = -0.12, P = 0.91. CONCLUSION: Our results demonstrated that the PPARγ2 Pro12Ala polymorphism might be risk-conferring locus for the progression of CAD among Caucasians, but not among Asians.

C282Y polymorphism in the HFE gene is associated with risk of breast cancer.

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Liu, Xiaoyan; Lv, Chunlei; Luan, Xiaorong; Lv, Ming

2013-10-01

The C282Y and H63D polymorphisms in the HFE gene have been implicated in susceptibility of breast cancer, but a number of studies have reported inconclusive results. The aim of this study is to investigate the association between the C282Y and H63D polymorphisms in the HFE gene and breast cancer risk by meta-analysis. We searched PubMed and Embase databases, covering all related studies until March 2, 2013. Statistical analysis was performed using STATA 10.0. A total of 7 studies including 1,720 cases and 18,296 controls for HFE C282Y polymorphism and 5 studies including 942 cases and 1,571 controls for HFE H63D polymorphism were included in the meta-analysis. The results showed that HFE C282Y polymorphism was significantly associated with increased risk of breast cancer under homozygotes vs. wild-type model (OR = 2.06, 95%CI = 1.19-3.58) and recessive model (OR = 1.98, 95%CI = 1.14-3.44) but not under heterozygotes vs. wild-type model (OR = 0.97, 95%CI = 0.70-1.35), dominant model (OR = 1.00, 95%CI = 0.72-1.40) and multiplicative model (OR = 1.04, 95%CI = 0.76-1.42). However, we did not find any association between HFE H63D polymorphism and breast cancer risk under all genetic models. This current meta-analysis suggested that C282Y polymorphism rather than H63D might be associated with increased risk of breast cancer.

[Polymorphism of CD209 and TLR3 genes in populations of North Eurasia].

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Barkhash, A V; Babenko, V N; Voevoda, M I; Romaschenko, A G

2016-06-01

The DC-SIGN (dendritic cell-specific intercellular adhesion molecule (ICAM)-3-grabbing non-integrin) and TLR3 (toll-like receptor 3) proteins are key effectors of the innate immunity and particularly play an important role in the organism’s antiviral defense as pattern-recognition receptors. Previously, we demonstrated that certain genotypes and alleles of single nucleotide polymorphisms (SNPs) rs2287886 (G/A) in the promoter region of the CD209 gene (encoding DC-SIGN) and rs3775291 (G/A, Leu412Phe) in the exon 4 of the TLR3 gene are associated with human predisposition to tick-borne encephalitis in the Russian population. In the present work, the distribution of genotype and allele frequencies for these SNPs was studied in seven populations of North Eurasia, including Caucasians (Russians and Germans (from Altai region)), Central Asian Mongoloids (Altaians, Khakass, Tuvinians, and Shorians), and Arctic Mongoloids (Chukchi). It was found that the CD209 gene rs2287886 SNP A/A genotype and A allele, as well as the TLR3 gene rs3775291 SNP G/G genotype and G allele (the frequencies of which in our previous studies were increased in tick-borne encephalitis patients as compared with the population control (Russian citizens of Novosibirsk)), are preserved with a high frequency in Central Asian Mongoloids (who for a long time regularly came in contact with tick-borne encephalitis virus in places of their habitation). We suggested that predisposition to tick-borne encephalitis in Central Asian Mongoloid populations can be predetermined by a different set of genes and their polymorphisms than in the Russian population.

Polymorphisms in phase I and phase II genes and breast cancer risk and relations to persistent organic pollutant exposure

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Ghisari, Mandana; Eiberg, Hans; Long, Manhai

2014-01-01

BACKGROUND: We have previously reported that chemicals belonging to the persistent organic pollutants (POPs) such as perfluorinated compounds (PFAS) and polychlorinated biphenyls (PCBs) are risk factors in Breast Cancer (BC) development in Greenlandic Inuit women. The present case-control study...... on BC risk in Greenlandic Inuit women. METHODS: The study population consisted of 31 BC cases and 115 matched controls, with information on serum levels of POPs. Genotyping was conducted for CYP1A1 (Ile462Val; rs1048943), CYP1B1 (Leu432Val; rs1056836), COMT (Val158Met; rs4680), CYP17A1 (A1> A2; rs743572...... aimed to investigate the main effect of polymorphisms in genes involved in xenobiotic metabolism and estrogen biosynthesis, CYP1A1, CYP1B1, COMT and CYP17, CYP19 and the BRCA1 founder mutation in relation to BC risk and to explore possible interactions between the gene polymorphisms and serum POP levels...

Peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk.

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Wang, Wei; Shao, Yan; Tang, Shenhua; Cheng, Xianyong; Lian, Haifeng; Qin, Chengyong

2015-01-01

The association between the peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk was inconclusive. We conducted a meta-analysis to evaluate the association between PPARγ Pro12Ala polymorphism and CRC risk. We searched Pubmed, EMBASE, and China National Knowledge Infrastructure databases. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A total of 17 case-control studies with 12635 and 15803 controls were included in this meta-analysis. Overall, PPARγ Pro12Ala polymorphism was associated with CRC risk (OR = 0.84, 95% CI 0.75-0.94, P = 0.003, I(2) = 35%). In the subgroup analysis by ethnicity, a significant association was found among Caucasians (OR = 0.85, 95% CI 0.75-0.96, P = 0.007, I(2) = 38%) but not among Asians (OR = 0.76, 95% CI 0.51-1.12, P = 0.17, I(2) = 28%). In the subgroup analysis by CRC site, a significant association was found among colon cancer (OR = 0.81, 95% CI 0.66-0.98, P = 0.03, I(2) = 16%) but not among rectal cancer (OR = 0.83, 95% CI 0.57-1.21, P = 0.34, I(2) = 63%). The sensitivity analysis did not influence the result by omitting low-quality studies (OR = 0.76, 95% CI 0.63-0.93, P = 0.006, I(2) = 51%). In conclusion, this meta-analysis suggested that PPARγ Pro12Ala polymorphism was significant associated with CRC risk.

Lipoprotein Lipase and PPAR Alpha Gene Polymorphisms, Increased Very-Low-Density Lipoprotein Levels, and Decreased High-Density Lipoprotein Levels as Risk Markers for the Development of Visceral Leishmaniasis by Leishmania infantum

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Márcia Dias Teixeira Carvalho

2014-01-01

Full Text Available In visceral leishmaniasis (VL endemic areas, a minority of infected individuals progress to disease since most of them develop protective immunity. Therefore, we investigated the risk markers of VL within nonimmune sector. Analyzing infected symptomatic and, asymptomatic, and noninfected individuals, VL patients presented with reduced high-density lipoprotein cholesterol (HDL-C, elevated triacylglycerol (TAG, and elevated very-low-density lipoprotein cholesterol (VLDL-C levels. A polymorphism analysis of the lipoprotein lipase (LPL gene using HindIII restriction digestion (N = 156 samples (H+ = the presence and H− = the absence of mutation revealed an increased adjusted odds ratio (OR of VL versus noninfected individuals when the H+/H+ was compared with the H−/H− genotype (OR = 21.3; 95% CI = 2.32–3335.3; P = 0.003. The H+/H+ genotype and the H+ allele were associated with elevated VLDL-C and TAG levels (P < 0.05 and reduced HDL-C levels (P < 0.05. An analysis of the L162V polymorphism in the peroxisome proliferator-activated receptor alpha (PPARα gene (n = 248 revealed an increased adjusted OR when the Leu/Val was compared with the Leu/Leu genotype (OR = 8.77; 95% CI = 1.41–78.70; P = 0.014. High TAG (P = 0.021 and VLDL-C (P = 0.023 levels were associated with susceptibility to VL, whereas low HDL (P = 0.006 levels with resistance to infection. The mutated LPL and the PPARα Leu/Val genotypes may be considered risk markers for the development of VL.

Acquisition through Horizontal Gene Transfer of Plasmid pSMA198 by Streptococcus macedonicus ACA-DC 198 Points towards the Dairy Origin of the Species

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Papadimitriou, Konstantinos; Anastasiou, Rania; Maistrou, Eleni; Plakas, Thomas; Papandreou, Nikos C.; Hamodrakas, Stavros J.; Ferreira, Stéphanie; Supply, Philip; Renault, Pierre; Pot, Bruno; Tsakalidou, Effie

2015-01-01

Background Streptococcus macedonicus is an intriguing streptococcal species whose most frequent source of isolation is fermented foods similarly to Streptococcus thermophilus. However, S. macedonicus is closely related to commensal opportunistic pathogens of the Streptococcus bovis/Streptococcus equinus complex. Methodology/Principal Findings We analyzed the pSMA198 plasmid isolated from the dairy strain Streptococcus macedonicus ACA-DC 198 in order to provide novel clues about the main ecological niche of this bacterium. pSMA198 belongs to the narrow host range pCI305/pWV02 family found primarily in lactococci and to the best of our knowledge it is the first such plasmid to be reported in streptococci. Comparative analysis of the pSMA198 sequence revealed a high degree of similarity with plasmids isolated from Lactococcus lactis strains deriving from milk or its products. Phylogenetic analysis of the pSMA198 Rep showed that the vast majority of closely related proteins derive from lactococcal dairy isolates. Additionally, cloning of the pSMA198 ori in L. lactis revealed a 100% stability of replication over 100 generations. Both pSMA198 and the chromosome of S. macedonicus exhibit a high percentage of potential pseudogenes, indicating that they have co-evolved under the same gene decay processes. We identified chromosomal regions in S. macedonicus that may have originated from pSMA198, also supporting a long co-existence of the two replicons. pSMA198 was also found in divergent biotypes of S. macedonicus and in strains isolated from dispersed geographic locations (e.g. Greece and Switzerland) showing that pSMA198’s acquisition is not a recent event. Conclusions/Significance Here we propose that S. macedonicus acquired plasmid pSMA198 from L. lactis via an ancestral genetic exchange event that took place most probably in milk or dairy products. We provide important evidence that point towards the dairy origin of this species. PMID:25584532

Towards understanding the tandem mass spectra of protonated oligopeptides. 2: The proline effect in collision-induced dissociation of protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp).

Science.gov (United States)

Bleiholder, Christian; Suhai, Sándor; Harrison, Alex G; Paizs, Béla

2011-06-01

The product ion spectra of proline-containing peptides are commonly dominated by y(n) ions generated by cleavage at the N-terminal side of proline residues. This proline effect is investigated in the current work by collision-induced dissociation (CID) of protonated Ala-Ala-Xxx-Pro-Ala (Xxx includes Ala, Ser, Leu, Val, Phe, and Trp) in an electrospray/quadrupole/time-of-flight (QqTOF) mass spectrometer and by quantum chemical calculations on protonated Ala-Ala-Ala-Pro-Ala. The CID spectra of all investigated peptides show a dominant y(2) ion (Pro-Ala sequence). Our computational results show that the proline effect mainly arises from the particularly low threshold energy for the amide bond cleavage N-terminal to the proline residue, and from the high proton affinity of the proline-containing C-terminal fragment produced by this cleavage. These theoretical results are qualitatively supported by the experimentally observed y(2)/b(3) abundance ratios for protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp). In the post-cleavage phase of fragmentation the N-terminal oxazolone fragment with the Ala-Ala-Xxx sequence and Pro-Ala compete for the ionizing proton for these peptides. As the proton affinity of the oxazolone fragment increases, the y(2)/b(3) abundance ratio decreases.

Association study of ghrelin receptor gene polymorphisms in rheumatoid arthritis.

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Robledo, G; Rueda, B; Gonzalez-Gay, M A; Fernández, B; Lamas, J R; Balsa, A; Pascual-Salcedo, D; García, A; Raya, E; Martín, J

2010-01-01

Ghrelin is a newly characterised growth hormone (GH) releasing peptide widely distributed that may play an important role in the regulation of metabolic balance in inflammatory diseases such as rheumatoid arthritis (RA) by decreasing the pro-inflammatory Th1 responses. In this study we investigated the possible contribution of several polymorphisms in the functional Ghrelin receptor to RA susceptibility. A screening of 3 single nucleotide polymorphisms (SNPs) was performed in a total of 950 RA patients and 990 healthy controls of Spanish Caucasian origin. Genotyping of all 3 SNPs was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. We observed no statistically significant deviation between RA patients and controls for the GHSR SNPs analysed. In addition, we performed a haplotype analysis that did not reveal an association with RA susceptibility. The stratification analysis for the presence of shared epitope (SE), rheumatoid factor (RF) or antibodies anti cyclic citrullinated peptide (anti-CCP) did not detect significant association of the GHSR polymorphisms with RA. These findings suggest that the GHSR gene polymorphisms do not appear to play a major role in RA genetic predisposition in our population.

Peptide (Lys-Leu) and amino acids (Lys and Leu) supplementations improve physiological activity and fermentation performance of brewer's yeast during very high-gravity (VHG) wort fermentation.

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Yang, Huirong; Zong, Xuyan; Cui, Chun; Mu, Lixia; Zhao, Haifeng

2017-12-22

Lys and Leu were generally considered as the key amino acids for brewer's yeast during beer brewing. In the present study, peptide Lys-Leu and a free amino acid (FAA) mixture of Lys and Leu (Lys + Leu) were supplemented in 24 °P wort to examine their effects on physiological activity and fermentation performance of brewer's yeast during very high-gravity (VHG) wort fermentation. Results showed that although both peptide Lys-Leu and their FAA mixture supplementations could increase the growth and viability, intracellular trehalose and glycerol content, wort fermentability, and ethanol content for brewer's yeast during VHG wort fermentation, and peptide was better than their FAA mixture at promoting growth and fermentation for brewer's yeast when the same dose was kept. Moreover, peptide Lys-Leu supplementation significantly increased the assimilation of Asp, but decreased the assimilation of Gly, Ala, Val, (Cys)2, Ile, Leu, Tyr, Phe, Lys, Arg, and Pro. However, the FAA mixture supplementation only promoted the assimilation of Lys and Leu, while reduced the absorption of total amino acids to a greater extent. Thus, the peptide Lys-Leu was more effective than their FAA mixture on the improvement of physiological activity, fermentation performance, and nitrogen metabolism of brewer's yeast during VHG wort fermentation. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

Recurrent pregnancy failure is associated with a polymorphism in the p53 tumour suppressor gene.

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Pietrowski, Detlef; Bettendorf, Hertha; Riener, Eva-Katrin; Keck, Christoph; Hefler, Lukas A; Huber, Johannes C; Tempfer, Clemens

2005-04-01

The p53 tumour suppressor gene is a well-known factor regulating apoptosis in a wide variety of cells and tissues. Alterations in the p53 gene are among the most common genetic changes in human cancers. In addition, recent data provide evidence that p53 plays a critical role in mediating pregnancy by regulating steroid hormone activation. In idiopathic recurrent miscarriages (IRM), causes and associations are much debated as the exact pathophysiological mechanisms are unknown. In this study, we assess whether an established polymorphism in the p53 gene is associated with the occurrence of IRM. Genotyping was performed by PCR-based amplification of the p53 Arg and Pro variants at codon 72 in 175 cases of IRM and 143 controls. We observed a statistically significant association between carriage of the Pro allele and the occurrence of IRM (P = 0.03, odds ratio 1.49, confidence interval 1.04-2.14). Distribution of genotypes was in Hardy-Weinberg equilibrium. Our results indicate an over-representation of the Pro allele of the p53 gene in women with IRM, giving support to the theory that p53 has a potential role during pregnancy.

Leptin receptor and ghrelin genes polymorphisms in relation to the metabolism of lipids

Directory of Open Access Journals (Sweden)

Anna Trakovická

2015-10-01

Full Text Available The aim of this work was to analyse genetic polymorphisms in genes encoding leptin receptor (LEPR and ghrelin (GHR as genetic markers of metabolic disorders in human nutrition. Genomic DNA was obtained from in total 84 human blood samples. Effect of analysed genetic markers was evaluated for three biochemical parameters: total cholesterol, HDL and LDL cholesterol. The PCR-RFLP method was used for identification of SNPs in LEPR (Gln223Arg and GHR (171T/C genes. In analysed population prevalence of heterozygous LEPRAG (47.62% and GHRCT (40.48% genotypes was observed. Frequency of LEPRA and LEPRB alleles were 0.55 and 0.45, respectively. Similar the GHRC allele had only slight predominance than GHRT allele (0.54/0.46. In population was found higher level of observed heterozygosity across loci (0.44. For both SNPs was found high effective allele number (1.98 which was also transferred to the median level of polymorphic information content (0.37. Association analysis of LEPR and GHR genotypes effect on selected biochemical parameters was performed using GLM procedure. Significant association was found only for levels of LDL cholesterol (P<0.01. Our study shows that both genes are involved in nutritional status and therefore can be considered as candidate genes of lipids metabolism disorders and obesity.

Association of pro-ghrelin and GHS-R1A gene polymorphisms and haplotypes with heavy alcohol use and body mass.

Science.gov (United States)

Landgren, Sara; Jerlhag, Elisabet; Zetterberg, Henrik; Gonzalez-Quintela, Arturo; Campos, Joaquin; Olofsson, Ulrica; Nilsson, Staffan; Blennow, Kaj; Engel, Jörgen A

2008-12-01

Ghrelin, an orexigenic peptide, acts on growth hormone secretagogue receptors (GHS-R1A), expressed in the hypothalamus as well as in important reward nodes such as the ventral tegmental area. Interestingly, ghrelin has been found to activate an important part of the reward systems, i.e., the cholinergic-dopaminergic reward link. Additionally, the rewarding and neurochemical properties of alcohol are, at least in part, mediated via this reward link. There is comorbidity between alcohol dependence and eating disorders. Thus, plasma levels of ghrelin are altered in patients with addictive behaviors such as alcohol and nicotine dependence and in binge eating disorder. This overlap prompted as to investigate the pro-ghrelin and GHS-R1A genes in a haplotype analysis of heavy alcohol-using individuals. A total of 417 Spanish individuals (abstainers, moderate, and heavy alcohol drinkers) were investigated in a haplotype analysis of the pro-ghrelin and GHS-R1A genes. Tag SNPs were chosen using HapMap data and the Tagger and Haploview softwares. These SNPs were then genotyped using TaqMan Allelic Discrimination. SNP rs2232165 of the GHS-R1A gene was associated with heavy alcohol consumption and SNP rs2948694 of the same gene as well as haplotypes of both the pro-ghrelin and the GHS-R1A genes were associated with body mass in heavy alcohol consuming individuals. The present findings are the first to disclose an association between the pro-ghrelin and GHS-R1A genes and heavy alcohol use, further strengthening the role of the ghrelin system in addictive behaviors and brain reward.

PPARγ gene polymorphism, C-reactive protein level, BMI and periodontitis in post-menopausal Japanese women.

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Wang, Yangming; Sugita, Noriko; Yoshihara, Akihiro; Iwasaki, Masanori; Miyazaki, Hideo; Nakamura, Kazutoshi; Yoshie, Hiromasa

2016-03-01

Several studies have reported inconsistent results regarding the association between the PPARγPro12Ala polymorphism and obesity. Obese individuals had higher C-reactive protein (CRP) levels compared with those of normal weight, and PPARγ activation could significantly reduce serum high-sensitive CRP level. We have previously suggested that the Pro12Ala polymorphism represents a susceptibility factor for periodontitis, which is a known risk factor for increased CRP level. The aim was to investigate associations between PPARγ gene polymorphism, serum CRP level, BMI and/or periodontitis among post-menopausal Japanese women. The final sample in this study comprised 359 post-menopausal Japanese women. Periodontal parameters, including PD, CAL and BOP, were measured per tooth. PPARγPro12Ala genotype was determined by PCR-RFLP. Hs-CRP value was measured by a latex nephelometry assay. No significant differences in age, BMI or periodontal parameters were found between the genotypes. The percentages of sites with PD ≥ 4 mm were significantly higher among the hsCRP ≥ 1 mg/l group than the hsCRP periodontitis, serum CRP level or BMI in post-menopausal Japanese women. However, serum hsCRP level correlated with periodontitis in Ala allele carriers, and with BMI in non-carriers. © 2014 John Wiley & Sons A/S and The Gerodontology Society. Published by John Wiley & Sons Ltd.

Agonist properties of a stable hexapeptide analog of neurotensin, N alpha MeArg-Lys-Pro-Trp-tLeu-Leu (NT1).

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Akunne, H C; Demattos, S B; Whetzel, S Z; Wustrow, D J; Davis, D M; Wise, L D; Cody, W L; Pugsley, T A; Heffner, T G

1995-04-18

The major signal transduction pathway for neurotensin (NT) receptors is the G-protein-dependent stimulation of phospholipase C, leading to the mobilization of intracellular free Ca2+ ([Ca2+]i) and the stimulation of cyclic GMP. We investigated the functional actions of an analog of NT(8-13), N alpha MeArg-Lys-Pro-Trp-tLeu-Leu (NT1), and other NT related analogs by quantitative measurement of the cytosolic free Ca2+ concentration in HT-29 (human colonic adenocarcinoma) cells using the Ca(2+)-sensitive dye fura-2/AM and by effects on cyclic GMP levels in rat cerebellar slices. The NT receptor binding affinities for these analogs to HT-29 cell membranes and newborn (10-day-old) mouse brain membranes were also investigated. Data obtained from HT-29 cell and mouse brain membrane preparations showed saturable single high-affinity sites and binding densities (Bmax) of 130.2 and 87.5 fmol/mg protein, respectively. The respective KD values were 0.47 and 0.39 nM, and the Hill coefficients were 0.99 and 0.92. The low-affinity levocabastine-sensitive site was not present (K1 > 10,000) in either membrane preparation. Although the correlation of binding between HT-29 cell membranes and mouse brain membranes was quite significant (r = 0.92), some of the reference agents had lower binding affinities in the HT-29 cell membranes. The metabolically stable compound NT1 plus other NT analogs and related peptides [NT, NT(8-13), xenopsin, neuromedin N, NT(9-13), kinetensin and (D-Trp11)-NT] increased intracellular Ca2+ levels in HT-29 cells, indicating NT receptor agonist properties. The effect of NT1 in mobilizing [Ca2+]i blocked by SR 48692, a non-peptide NT antagonist. Receptor binding affinities of NT analogs to HT-29 cell membranes were positively correlated with potencies for mobilizing intracellular calcium in the same cells. In addition, NT1 increased cyclic GMP levels in rat cerebellar slices, confirming the latter findings of its NT agonist action. These results substantiate

Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome.

Science.gov (United States)

Baldani, Dinka Pavicic; Skrgatic, Lana; Cerne, Jasmina Z; Ferk, Polonca; Simunic, Velimir; Gersak, Ksenija

2014-03-01

Insulin resistance is one of the key factors in the pathogenesis of polycystic ovary syndrome (PCOS). The peroxisome proliferator-activated receptor gamma (PPARG) plays a role in the regulation of insulin sensitivity. The aim of the present study was to establish a possible association of the PPARG Pro12Ala polymorphism with PCOS and its effect on family and personal history, as well as on the metabolic and endocrine parameters in PCOS patients. A total of 151 PCOS patients and 179 healthy women of reproductive age were enrolled. History, body mass index (BMI), waist-to-hip ratio and the presence of phenotypic hyperandrogenism were recorded. Hormonal, metabolic and biochemical profiles were assessed. A molecular analysis for the genetic polymorphism was performed. One third (29.8%) of the PCOS patients were found to be carriers of at least one variant of the Ala allele (X/Ala), while 70.2% carried two wild-type Pro alleles (Pro/Pro), with an equal distribution observed in the control group. The PCOS patients carrying the X/Ala alleles exhibited lower serum fasting insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and BMI compared to Pro/Pro carriers. This finding was significant only in the lean PCOS group. The polymorphic genotype exerted no effect on history, hormonal and clinical hyperandrogenism, lipid status or C-reactive protein, leptin, adiponectin, resistin and ghrelin serum levels in women with PCOS. In conclusion, although the PPARG Pro12Ala polymorphism is not a major determinant of PCOS in the Croatian population, it may exert a positive effect on insulin sensitivity and BMI. As these associations were recorded exclusively in the lean group of patients with PCOS, this polymorphism potentially contributes to a protective role against hyperinsulinemia and obesity.

Determination of the frequency of polymorphisms in genes related to the genome stability maintenance of the population residing at Monte Alegre, PA (Brazil) municipality

International Nuclear Information System (INIS)

Hozumi, Cristiny Gomes

2010-01-01

The human exposure to ionizing radiation coming from natural sources is an inherent feature of human life on earth, for man and all living things have always been exposed to these sources. Ionizing radiation is a known genotoxic agent which can affect the genomic stability and genes related to DNA repair may play a role when they have committed certain polymorphism. This study aimed to analyze the frequency of polymorphisms (SNPs) in genes of DNA repair and cell cycle control: hOGG1 (Ser326Cys), XRCC3 (Thr241 Met) and p53 (Arg72Pro) in saliva samples from a population located Monte Alegre, state of Para were collected in August 2008 and 40 samples of men and 46 samples of women, adding a total of 86 samples. By RFLP was determined the frequency of homozygous genotypes and / or heterozygous for polymorphic genes. The I)OGG1 gene was 5% of the allele 326Cys, XRCC3 gene found about 21 % of the allele 241 Met and p53 gene showed 40.8% of the 72Pro allele. And the genotype frequencies of individuals for the three genes were 91.04%, 88.06% and 59.7% for homozygous wild genotype, 5.97%, 11.94% and 22.39% for heterozygote genotype and 2,99%, zero and 17:91% for homozygous polymorphic hOGG1 genes respectively, XRCC3, p53. These values are similar to those found in previous studies. The influence of these polymorphisms, which are involved in DNA repair and consequent genotoxicity induced by radiation depends on dose and exposure factors such as smoking, which is statistically a factor in public health surveillance in the region. This study gathered information and molecular epidemiology in Monte Alegre, that help to characterization of local population. (author)

Combined effects of NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism and smoking on bladder cancer risk: Two meta-analyses.

Science.gov (United States)

Wang, Xiao-Chun; Wang, Jian; Tao, Hui-Hui; Zhang, Chao; Xu, Li-Fa

2017-07-14

Objectives: Cigarette smoking is the major risk factor of bladder cancer via exposure to chemical carcinogens. Nicotinamide adenine dinucleotide phosphate (NADP+): quinine oxidoreductase 1 (NQO1) and sulfotransferase 1A1 (SULT1A1) have been reported to involve in the metabolism of polycyclic aromatic hydrocarbons (PAHs) and aromatic amines. Therefore, the risk of bladder cancer (BC) may be influenced by polymorphisms in the genes that modulate metabolic detoxification in particular by interacting with cigarette smoking. Considering the limited power by the individual studies with a relatively small sample size, especially when analyzing the combined effect of polymorphisms in NQO1 and SULT1A1 genes and smoking, these 2 meta-analyses have aimed to clarify the combined effects of them on BC risk by integrating related studies. Two meta-analyses included 1341 cases and 1346 controls concerning NQO1 Pro187Ser and smoking, and 1921 cases and 1882 controls on SULT1A1 Arg213His and smoking were performed. Odds ratios (OR) and 95% confidence intervals (CI) were used for assessing the strength of the association. The result has demonstrated that smokers with NQO1 Pro/Ser or Ser/Ser genotypes have a prominent association with the risk of BC as compared with non-smokers with NQO1 Pro/Pro genotype, with OR equal to 3.71 (95% CI: 2.87-4.78, pheterogeneity = 0.376). Besides, smokers carrying SULT1A1 Arg/Arg genotypes were observed to confer 2.38 fold increased risk of BC (95% CI: 1.44-3.93, pheterogeneity = 0.001) when compared with non-smokers with SULT1A1 Arg/Arg or His/His genotypes. These findings have suggested that the NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism combination with smoking significantly confer susceptibility to BC. Int J Occup Med Environ Health 2017;30(5):791-802. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Combined effects of NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism and smoking on bladder cancer risk: Two meta-analyses

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Xiao-Chun Wang

2017-10-01

Full Text Available Objectives: Objectives: Cigarette smoking is the major risk factor of bladder cancer via exposure to chemical carcinogens. Nicotinamide adenine dinucleotide phosphate (NADP+: quinine oxidoreductase 1 (NQO1 and sulfotransferase 1A1 (SULT1A1 have been reported to involve in the metabolism of polycyclic aromatic hydrocarbons (PAHs and aromatic amines. Therefore, the risk of bladder cancer (BC may be influenced by polymorphisms in the genes that modulate metabolic detoxification in particular by interacting with cigarette smoking. Considering the limited power by the individual studies with a relatively small sample size, especially when analyzing the combined effect of polymorphisms in NQO1 and SULT1A1 genes and smoking, these 2 meta-analyses have aimed to clarify the combined effects of them on BC risk by integrating related studies. Material and Methods: Two meta-analyses included 1341 cases and 1346 controls concerning NQO1 Pro187Ser and smoking, and 1921 cases and 1882 controls on SULT1A1 Arg213His and smoking were performed. Odds ratios (OR and 95% confidence intervals (CI were used for assessing the strength of the association. Results: The result has demonstrated that smokers with NQO1 Pro/Ser or Ser/Ser genotypes have a prominent association with the risk of BC as compared with non-smokers with NQO1 Pro/Pro genotype, with OR equal to 3.71 (95% CI: 2.87–4.78, pheterogeneity = 0.376. Besides, smokers carrying SULT1A1 Arg/Arg genotypes were observed to confer 2.38 fold increased risk of BC (95% CI: 1.44–3.93, pheterogeneity = 0.001 when compared with non-smokers with SULT1A1 Arg/Arg or His/His genotypes. Conclusions: These findings have suggested that the NQO1 Pro187Ser or SULT1A1 Arg213His polymorphism combination with smoking significantly confer susceptibility to BC. Int J Occup Med Environ Health 2017;30(5:791–802

[The association of polymorphisms in SLC18A1, TPH1 and RELN genes with risk of paranoid schizophrenia].

Science.gov (United States)

Galaktionova, D Iu; Gareeva, A E; Khusnutdinova, E K; Nasedkina, T V

2014-01-01

We have developed a biochip for the analysis of polymorphisms in candidate genes for schizophrenia: DISC1, RELN, ZNF804A, PLXNA2, COMT, SLC18A41, CACNA1C, ANK3, TPH1, PLAA and SNAP-25. Using biochip the allele and genotype frequencies in 198 patients with schizophrenia and 192 healthy individuals have been obtained. For SLC18A1 polymorphism rs2270641 A>C, the frequencies of A allele (p = 0.007) and AA genotype (p = 0.002) were lower in patients compared with healthy individuals. A significant association was found between AA genotype (p = 0.036) of the TPH1 polymorphism rs1800532 C>A and schizophrenia. The C allele (p = 0.039) of the RELNpolymorphism rs7341475 C>T were lower in patients with schizophrenia compared with healthy individuals in a tatar population. Genotype AA of the TPH1 polymorphism rs1800532 C>A were more frequent in patients with schizophrenia compared with healthy individuals. Ithas been shown that the C allele (p = 0.0001) and GC (p = = 0.0001) genotype of the PLXNA2 polymorphism rs1327175 G>C are associated with the family history in patients with paranoid schizophrenia. The obtained data suggest that SLC18A1, TPH1 and RELN gene polymorphisms are associated with the risk of paranoid schizophrenia.

The Pai-associated leuX specific tRNA5(Leu) affects type 1fimbriation in pathogenic Escherichia coli by control of FimB recombinase expression

DEFF Research Database (Denmark)

Ritter, A.; Gally, D.; Olsen, Peter Bjarke

1997-01-01

The uropathogenic Escherichia coli strain 536 (06:K15:H31) carries two large chromosomalpathogenicity islands (Pais). Both Pais are flanked by tRNA genes. Spontaneous deletion of Pai IIresults in truncation of the leuX tRNA5Leu gene. This tRNA is required for the expression of type 1fimbriae (Fim...

Inflammatory Gene Polymorphisms in Lung Cancer Susceptibility.

Science.gov (United States)

Eaton, Keith D; Romine, Perrin E; Goodman, Gary E; Thornquist, Mark D; Barnett, Matt J; Petersdorf, Effie W

2018-05-01

Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the β-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [IFNG], interleukin 10 gene [IL10], interleukin 1 alpha gene [IL1A], interleukin 1 beta gene [IL1B], interleukin 2 gene [IL2], interleukin 4 receptor gene [IL4R], interleukin 4 gene [IL4], interleukin 6 gene [IL6], prostaglandin-endoperoxide synthase 2 gene [PTGS2] (also known as COX2), transforming growth factor beta 1 gene [TGFB1], and tumor necrosis factor alpha gene [TNFA]) was evaluated. Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1β-511C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58-0.94] and OR = 0.71 [95% CI: 0.50-1.01], respectively, p = 0.03). Similar results were observed for the IL-1β-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59-0.95] and OR = 0.69 [95% CI: 0.46-1.03], respectively, p = 0.03). Survival was not influenced by genotype. This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Analysis of single nucleotide polymorphisms of CRYGA and CRYGB genes in control population of western Indian origin

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Kapur Suman

2009-01-01

Full Text Available Aim: Polymorphisms in γ-crystallins ( CRYG can serve as markers for lens differentiation and eye disorders leading to cataract. Several investigators have reported the presence of sequence variations within crystallin genes, with or without apparent effects on the function of the proteins both in mice and humans. Delineation of these polymorphic sites may explain the differences observed in the susceptibility to cataract observed among various ethnic groups. An easier Restriction Fragment Length Polymorphism (RFLP-based method has been used to detect the frequency of four single nucleotide polymorphisms (SNPs in CRYGA / CRYGB genes in control subjects of western Indian origin. Materials and Methods: A total of 137 healthy volunteers from western India were studied. Examination was performed to exclude volunteers with any ocular defects. Polymerase chain reaction (PCR-RFLP based method was developed for genotyping of G198A (Intron A, T196C (Exon 3 of CRYGA and T47C (Promoter, G449T (Exon 2 of CRYGB genes. Results: The exonic SNPs in CRYGA and CRYGB were found to have an allele frequency 0.03 and 1.00 for ancestral allele respectively, while frequency of non-coding SNP in CRYGA was 0.72. Allele frequency of T90C of CRYGB varied significantly ( P = 0.02 among different age groups. An in-silico analysis reveals that this sequence variation in CRYGB promoter impacts the binding of two transcription factors, ACE2 (Member of CLB2 cluster and Progesterone Receptor (PR which may impact the expression of CRYGB gene. Conclusions: This study establishes baseline frequency data for four SNPs in CRYGA and CRYGB genes for future case control studies on the role of these SNPs in the genetic basis of cataract.

Meta-analysis of association between the TP53 Arg72Pro polymorphism and risk of endometriosis based on case-control studies.

Science.gov (United States)

Yan, Yulan; Wu, Renzheng; Li, Shaojing; He, Jinlong

2015-06-01

In the light of the relationship between the TP53 Arg72Pro (rs1042522) polymorphism and the risk of endometriosis remains inclusive or controversial. For better understanding of the effect of TP53 Arg72Pro polymorphism on endometriosis risk, we performed a meta-analysis. The relevant studies were identified through a search of PubMed, Web of Science, EMBASE, Ovid, Springer, China National Knowledge Infrastructure (CNKI), cqvip, Wanfang database, and Chinese Biomedical Literature (CBM) databases up to December, 2014. The association between the TP53 Arg72Pro polymorphism and endometriosis risk was pooled by conducted by odds ratios and 95% confidence intervals. A total of fifteen case-control studies with 2683 cases and 3335 controls were eventually identified. There was significant association between Arg72Pro polymorphism and endometriosis risk in all of the five models in overall populations (C vs. G: OR=1.32, 95%CI=1.14-1.53, p=0.00; CC vs. GG: OR=1.80, 95%CI=1.28-2.53, p=0.001; GC vs. GG: OR=1.52, 95%CI=1.22-1.88, p=0.00; CC vs. OR=1.32, 95%CI=1.05-1.66, p=0.016; CC/GC vs. GG: OR=1.59, 95%CI=1.26-2.00, p=0.00). In the sub-group analysis according to ethnicity, the results suggested that TP53 Arg72Pro polymorphism was not associated with endometriosis risk in Caucasians. However, the significant association was found in Asians and Mixed race (MIX) under the five models. The results of this meta-analysis suggest that the TP53 Arg72Pro polymorphism can increase the risk of endometriosis, especially among Asians and MIX populations. Considering the limited sample size and ethnicities included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Girl with Autoimmune Cytopenias, Nonmalignant Lymphadenopathy, and Recurrent Infections

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Marjolein A. C. Mattheij

2012-01-01

Full Text Available We describe a girl, now 9 years of age, with chronic idiopathic thrombocytopenic purpura, persistent nonmalignant lymphadenopathy, splenomegaly, recurrent infections, and autoimmune hemolytic anemia. Her symptoms partly fit the definitions of both autoimmune lymphoproliferative syndrome (ALPS and common variable immunodeficiency disorders (CVIDs. Genetic analysis showed no abnormalities in the ALPS-genes FAS, FASLG, and CASP10. The CVID-associated TACI gene showed a homozygous polymorphism (Pro251Leu, which is found also in healthy controls.

Methylenetetrahydrofolate reductase gene polymorphism in type 1 ...

African Journals Online (AJOL)

In patients with type-I diabetes mellitus folate deficiency is associated with endothelial dysfunction. So, polymorphism in genes involved in folate metabolism may have a role in vascular disease. This study was designed to evaluate the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism ...

Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer

International Nuclear Information System (INIS)

Sáenz-López, Pablo; Carretero, Rafael; Cózar, José Manuel; Romero, José Maria; Canton, Julia; Vilchez, José Ramón; Tallada, Miguel; Garrido, Federico; Ruiz-Cabello, Francisco

2008-01-01

Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk. A case-control study design was used to test the association between prostate cancer risk and the polymorphisms TNF-A-308 A/G (rs 1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587) and MCP-1 2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area. Diagnosis of prostate cancer was significantly associated with TNF-A GA + AA genotype (OR, 1.61; 95% CI, 1.09–2.64) and RANTES GA + AA genotype (OR, 1.44; 95% CI, 1.09–2.38). A alleles in TNF-A and RANTES influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and IL1-A or MCP-1 polymorphisms. Our results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development

Association Between ACE Gene Polymorphism and QT Dispersion in Patients with Acute Myocardial Infarction.

Science.gov (United States)

Karahan, Zulkuf; Ugurlu, Murat; Ucaman, Berzal; Veysel Ulug, Ali; Kaya, Ilyas; Cevik, Kemal; Sahin Adiyaman, Mehmet; Oztürk, Onder; Iyem, Hikmet; Ozdemir, Ferit

2016-01-01

Angiotensin converting enzyme (ACE) gene polymorphism is associated with high renin-angiotensin system causing myocardial fibrosis and ventricular repolarization abnormality. Based on these findings, this study was designed to determine the association between ACE gene insertion/deletion (I/D) polymorphism and QT dispersion after acute myocardial infarction (MI). The study included 108 patients with acute MI. Blood samples were obtained from all the patients for genomic DNA analysis. ECGs were recorded at baseline and at the end of a 6-month follow up. The OT dispersion was manually calculated. The mean age of the patients was 57.5 ±9.9 years (ranging from 36 to 70). The patients with DD genotype showed longer QT dispersion than patients with II or DI genotype at the baseline, while at the end of the six-month follow up the patients with DI genotype showed longer QT dispersion than patients with DD or II genotypes. However, the magnitude of the QT dispersion prolongation was higher in patients carrying the ACE D allele than patients who were not carrying it, at baseline and at the end of six-month follow up (52.5 ±2.6 msn vs. 47.5±2.1 msn at baseline, 57±3.2 msn vs. 53±2.6 msn in months, P: 0.428 and P: 0.613, respectively). Carriers of the D allele of ACE gene I/D polymorphism may be associated with QT dispersion prolongation in patients with MI.An interaction of QT dispersion and ACE gene polymorphism may be associated with an elevation of serum type I-C terminal pro-collagen concentration, possibly leading to myocardial fibrosis, and increased action potential duration.

Genetic polymorphisms in CYP1A1, CYP1B1 and COMT genes in Greenlandic Inuit and Europeans.

Science.gov (United States)

Ghisari, Mandana; Long, Manhai; Bonefeld-Jørgensen, Eva C

2013-01-01

The Indigenous Arctic population is of Asian descent, and their genetic background is different from the Caucasian populations. Relatively little is known about the specific genetic polymorphisms in genes involved in the activation and detoxification mechanisms of environmental contaminants in Inuit and its relation to health risk. The Greenlandic Inuit are highly exposed to legacy persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), and an elucidation of gene-environment interactions in relation to health risks is needed. The aim of this study was to determine and compare the genotype and allele frequencies of the cytochrome P450 CYP1A1 Ile462Val (rs1048943), CYP1B1 Leu432Val (rs1056836) and catechol-O-methyltransferase COMT Val158Met (rs4680) in Greenlandic Inuit (n=254) and Europeans (n=262) and explore the possible relation between the genotypes and serum levels of POPs. The genotype and allele frequency distributions of the three genetic polymorphisms differed significantly between the Inuit and Europeans. For Inuit, the genotype distribution was more similar to those reported for Asian populations. We observed a significant difference in serum polychlorinated biphenyl (CB-153) and the pesticide 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) levels between Inuit and Europeans, and for Inuit also associations between the POP levels and genotypes for CYP1A1, CYP1B1 and COMT. Our data provide new information on gene polymorphisms in Greenlandic Inuit that might support evaluation of susceptibility to environmental contaminants and warrant further studies.

Gene polymorphisms in chronic periodontitis

NARCIS (Netherlands)

Laine, M.L.; Loos, B.G.; Crielaard, W.

2010-01-01

We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP) susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or

gene polymorphism and its serum lev

Indian Academy of Sciences (India)

Navya

polymorphisms and its serum level with the risk of MetS as well as their ... population for quantifying insulin resistance and β-cell function (Matthews et al. 1985). .... of IL-10 -819 C >T gene polymorphism (Co-dominant model) was significantly.

-765 G>C POLYMORPHISM OF THE COX-2 GENE AND GASTRIC CANCER RISK IN BRAZILIAN POPULATION

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Vanessa Maria de Lima Pazine CAMPANHOLO

2014-04-01

Full Text Available Context Genomic alterations play important roles in gastric cancer carcinogenesis. Cyclooxygenases (COX are important enzymes in the maintenance of mucosal integrity and in pathological processes, mainly in inflammation and cancer. The -765G>C COX-2 polymorphism has been implicated in gastric cancer risk. Objectives To evaluate the COX-2 gene polymorphism as a predictor of gastric cancer risk. Methods One hundred gastric cancer patients and 150 controls were enrolled from a Brazilian centre. Personal data regarding related risk factors, including alcohol consumption and smoking behavior, were collected via questionnaire. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism. Results G/G, G/C and C/C genotypes frequencies was 42.7%, 50% and 7.3%, respectively in controls and 59.0%, 34.0% and 7.0% in gastric cancer. The frequency of the genotypes differed between the groups (P = 0.033. A higher risk of gastric cancer was associated with COX-2 -765G/G genotype (P = 0.048; OR:1.98, 95% CI = 1.01-3.90. Alcohol consumption and smoking in patients with -765G/G genotype also increased the risk of gastric cancer. Conclusions The -765G/G genotype and the -765G allele had been associated with an increased risk for gastric cancer. The presence of smoking and alcohol consumption increased the risk for gastric cancer in subjects with -765G/G genotype compared with the control group. Polymorphism of COX-2 gene and gastric cancer risk.

Ancestral Variations of the PCDHG Gene Cluster Predispose to Dyslexia in a Multiplex Family

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Teesta Naskar

2018-02-01

Full Text Available Dyslexia is a heritable neurodevelopmental disorder characterized by difficulties in reading and writing. In this study, we describe the identification of a set of 17 polymorphisms located across 1.9 Mb region on chromosome 5q31.3, encompassing genes of the PCDHG cluster, TAF7, PCDH1 and ARHGAP26, dominantly inherited with dyslexia in a multi-incident family. Strikingly, the non-risk form of seven variations of the PCDHG cluster, are preponderant in the human lineage, while risk alleles are ancestral and conserved across Neanderthals to non-human primates. Four of these seven ancestral variations (c.460A > C [p.Ile154Leu], c.541G > A [p.Ala181Thr], c.2036G > C [p.Arg679Pro] and c.2059A > G [p.Lys687Glu] result in amino acid alterations. p.Ile154Leu and p.Ala181Thr are present at EC2: EC3 interacting interface of γA3-PCDH and γA4-PCDH respectively might affect trans-homophilic interaction and hence neuronal connectivity. p.Arg679Pro and p.Lys687Glu are present within the linker region connecting trans-membrane to extracellular domain. Sequence analysis indicated the importance of p.Ile154, p.Arg679 and p.Lys687 in maintaining class specificity. Thus the observed association of PCDHG genes encoding neural adhesion proteins reinforces the hypothesis of aberrant neuronal connectivity in the pathophysiology of dyslexia. Additionally, the striking conservation of the identified variants indicates a role of PCDHG in the evolution of highly specialized cognitive skills critical to reading.

Alpha-1 antitrypsin deficiency caused by a novel mutation (p.Leu263Pro: Pi*ZQ0gaia – Q0gaia allele

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M.J. Oliveira

2015-11-01

Full Text Available Severe alpha-1 antitrypsin deficiency (AATD is generally associated with PI*ZZ genotype and less often with combinations of PI*Z, PI*S, and other rarer deficiency or null (Q0 alleles. Severe AATD predisposes patients to various diseases, including pulmonary emphysema. Presented here is a case report of a young man with COPD and AATD. The investigation of the AATD showed a novel mutation p.Leu263Pro (c.860T>C, which was named Q0gaia (Pi*ZQ0gaia. Q0gaia is associated with very low or no detectable serum concentrations of AAT. Keywords: Alpha-1 antitrypsin deficiency, Null allele, COPD

Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography

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Fujimoto Kei

2007-09-01

Full Text Available Abstract Background Although oxidative stress by accumulation of reactive oxygen species (ROS in diabetes has become evident, it remains unclear what genes, involved in redox balance, would determine susceptibility for development of atherosclerosis in diabetes. This study evaluated the effect of genetic polymorphism of enzymes producing or responsible for reducing ROS on coronary artery calcification in type 2 diabetes (T2D. Methods An index for coronary-arteriosclerosis, coronary artery calcium score (CACS was evaluated in 91 T2D patients using a multi-slice computed tomography. Patients were genotyped for ROS-scavenging enzymes, Glutathione peroxidase-1 (GPx-1, Catalase, Mn-SOD, Cu/Zn-SOD, as well as SNPs of NADPH oxidase as ROS-promoting elements, genes related to onset of T2D (CAPN10, ADRB3, PPAR gamma, FATP4. Age, blood pressure, BMI, HbA1c, lipid and duration of diabetes were evaluated for a multivariate regression analysis. Results CACS with Pro/Leu genotype of the GPx-1 gene was significantly higher than in those with Pro/Pro (744 ± 1,291 vs. 245 ± 399, respectively, p = 0.006. In addition, genotype frequency of Pro/Leu in those with CACS ≥ 1000 was significantly higher than in those with CACS OR = 3.61, CI = 0.97–13.42; p = 0.045 when tested for deviation from Hardy-Weinberg's equilibrium. Multivariate regression analyses revealed that CACS significantly correlated with GPx-1 genotypes and age. Conclusion The presence of Pro197Leu substitution of the GPx-1 gene may play a crucial role in determining genetic susceptibility to coronary-arteriosclerosis in T2D. The mechanism may be associated with a decreased ability to scavenge ROS with the variant GPx-1.

Association of Genetic Polymorphism in the Interleukin-8 Gene with Risk of Oral Cancer and Its Correlation with Pain.

Science.gov (United States)

Singh, Prithvi Kumar; Chandra, Girish; Bogra, Jaishri; Gupta, Rajni; Kumar, Vijay; Hussain, Syed Rizwan; Jain, Amita; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem

2016-02-01

Oral cancer is a multifactorial disease process and involves complex interactions between gene to gene and gene to environmental factors. Interleukin 8 (IL-8), a pro-inflammatory cytokine, having angiogenic activity with elevated expression in tumor cells, is reported to play an essential role in oral cancer development. This study was conducted with the aim to investigate the role of IL-8 (-A251T) gene polymorphism in susceptibility, progression, and self-reporting pain in oral cancer. The single nucleotide polymorphisms of the IL-8 (-A251T) gene were screened in 300 patients with oral cancer and 300 healthy controls, by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele frequencies were evaluated by chi-square test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. The results of the study demonstrated that IL-8 (-A251T) gene polymorphism was significantly associated with susceptibility of oral cancer, whereas its correlation with clinico-pathological status or pain due to oral cancer could not be established. The AT heterozygous (OR 5.31; CI 3.38-8.34; p 0.0001) and AA homozygous (OR 2.89; CI 1.76-4.75; p 0.0001) had a greater risk for oral cancer compared to TT homozygous. Furthermore, significantly increased values of A allele frequencies compared to T allele were observed in all patients (OR 1.56; CI 1.24-1.96; p 0.0002). Tobacco chewing and smoking were also found to influence the development of oral cancer and increased the incidence of pain in oral cancer patients. The findings of this study suggest that the IL-8 (-A251T) gene polymorphism may be associated with increased risk of oral cancer.

Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro).

Science.gov (United States)

Yuca, Sevil Ari; Rendtorff, Nanna Dahl; Boulahbel, Houda; Lodahl, Marianne; Tranebjærg, Lisbeth; Cesur, Yasar; Dogan, Murat; Yilmaz, Cahide; Akgun, Cihangir; Acikgoz, Mehmet

2012-01-01

Wolfram syndrome, also named "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an inherited association of juvenile-onset diabetes mellitus and optic atrophy as key diagnostic criteria. Renal tract abnormalities and neurodegenerative disorder may occur in the third and fourth decade. The wolframin gene, WFS1, associated with this syndrome, is located on chromosome 4p16.1. Many mutations have been described since the identification of WFS1 as the cause of Wolfram syndrome. We identified a new homozygous WFS1 mutation (c.1532T>C; p.Leu511Pro) causing Wolfram syndrome in a large inbred Turkish family. The patients showed early onset of IDDM, diabetes insipidus, optic atrophy, sensorineural hearing impairment and very rapid progression to renal failure before age 12 in three females. Ectopic expression of the wolframin mutant in HEK cells results in greatly reduced levels of protein expression compared to wild-type wolframin, strongly supporting that this mutation is disease-causing. The mutation showed perfect segregation with disease in the family, characterized by early and severe clinical manifestations. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Development of a tetra-primer ARMS-PCR for detecting the E198A SNP in the isotype-1 β-tubulin gene of Haemonchus contortus populations in China.

Science.gov (United States)

Zongze, Zhang; Xin, Yang; Awais, Ali Ahmad; Weiqiang, Lei; Chunqun, Wang; Di, Wenda; Yanqin, Zhou; Junlong, Zhao; Rui, Fang; Min, Hu

2018-03-15

The tetra-primer ARMS-PCR is a rapid, simple and low cost method for single nucleotide polymorphism (SNP) genotyping and has been used to detect SNPs associated with diseases and drug resistance. E198A in the isotype-1 β-tubulin gene is one of the three SNPs associated with benzimidazole resistance in parasitic nematode Haemonchus contortus. However, up to now, only PCR-RFLP method was used to test E198A in H. contortus. In the present study, we developed a tetra-primer ARMS-PCR to detect E198A in H. contortus and the accuracy of the results was compared with that of PCR-coupled sequencing. The results showed that optimization of PCR reaction system, especially the proportion of the amount of inner and outer primers, could achieve desirable amplification effect. Three different profiles displaying three distinct genotypes could be identified clearly and intuitively on the agarose gel where the samples with amplified PCR products containing two bands of 433 bp and 200 bp in size indicated susceptible homozygous (SS), those with PCR products containing two bands of 433 bp and 284 bp in length indicated resistant homozygous (RR) and the samples with amplified PCR products containing three bands of 433 bp, 284 bp and 200 bp in size indicated heterozygous (RS). The results showed that the established method can be successfully applied to the detection of E198A in H. contortus, which has high accuracy and is easy to perform. Copyright © 2018 Elsevier B.V. All rights reserved.

Evidence that the mitochondrial leucyl tRNA synthetase (LARS2) gene represents a novel type 2 diabetes susceptibility gene

DEFF Research Database (Denmark)

hart, Leen M; Hansen, Torben; Rietveld, Ingrid

2005-01-01

Previously, we have shown that a mutation in the mitochondrial DNA-encoded tRNA(Leu(UUR)) gene is associated with type 2 diabetes. One of the consequences of this mutation is a reduced aminoacylation of tRNA(Leu(UUR)). In this study, we have examined whether variants in the leucyl tRNA synthetase...... gene (LARS2), involved in aminoacylation of tRNA(Leu(UUR)), associate with type 2 diabetes. Direct sequencing of LARS2 cDNA from 25 type 2 diabetic subjects revealed eight single nucleotide polymorphisms. Two of the variants were examined in 7,836 subjects from four independent populations...... in the Netherlands and Denmark. A -109 g/a variant was not associated with type 2 diabetes. Allele frequencies for the other variant, H324Q, were 3.5% in type 2 diabetic and 2.7% in control subjects, respectively. The common odds ratio across all four studies was 1.40 (95% CI 1.12-1.76), P = 0.004. There were...

Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women with Polycystic Ovary Syndrome

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Moushira Zaki

2017-06-01

CONCLUSION: The PPARG Pro12Ala polymorphism might contribute to the risk of PCOS and abnormal metabolic parameters and could be considered as a biomarker for early diagnosis and clinic prediction of metabolic complications.

Effects of BDNF polymorphisms on antidepressant action.

Science.gov (United States)

Tsai, Shih-Jen; Hong, Chen-Jee; Liou, Ying-Jay

2010-12-01

Evidence suggests that the down-regulation of the signaling pathway involving brain-derived neurotrophic factor (BDNF), a molecular element known to regulate neuronal plasticity and survival, plays an important role in the pathogenesis of major depression. The restoration of BDNF activity induced by antidepressant treatment has been implicated in the antidepressant therapeutic mechanism. Because there is variability among patients with major depressive disorder in terms of response to antidepressant treatment and since genetic factors may contribute to this inter-individual variability in antidepressant response, pharmacogenetic studies have tested the associations between genetic polymorphisms in candidate genes related to antidepressant therapeutic action. In human BDNF gene, there is a common functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF. Because of the potentially important role of BDNF in the antidepressant mechanism, many pharmacogenetic studies have tested the association between this polymorphism and the antidepressant therapeutic response, but they have produced inconsistent results. A recent meta-analysis of eight studies, which included data from 1,115 subjects, suggested that the Val/Met carriers have increased antidepressant response in comparison to Val/Val homozygotes, particularly in the Asian population. The positive molecular heterosis effect (subjects heterozygous for a specific genetic polymorphism show a significantly greater effect) is compatible with animal studies showing that, although BDNF exerts an antidepressant effect, too much BDNF may have a detrimental effect on mood. Several recommendations are proposed for future antidepressant pharmacogenetic studies of BDNF, including the consideration of multiple polymorphisms and a haplotype approach, gene-gene interaction, a single antidepressant regimen, controlling for age and gender interactions, and pharmacogenetic

Polymorphism of the VEGF gene and its association with growth ...

African Journals Online (AJOL)

User

Keywords: VEGF gene, caprine, single nucleotide polymorphism (SNP), genetic variation, PCR-SSCP ... This field is strongly focusing on gene loci and polymorphisms that have ..... Enhance the efficiency of single-strand conformation polymorphism analysis by short polyacrylamide gel and modified silver staining. Anal.

Resistance mutations of Pro197, Asp376 and Trp574 in the acetohydroxyacid synthase (AHAS) affect pigments, growths, and competitiveness of Descurainia sophia L.

Science.gov (United States)

Zhang, Yongzhi; Xu, Yufang; Wang, Shipeng; Li, Xuefeng; Zheng, Mingqi

2017-11-27

D. Sophia is one of the most problematic weed species infesting winter wheat in China, and has evolved high resistance to tribenuron-methyl. Amino acid substitutions at site of Pro197, Asp376 and Trp574 in acetohydroxyacid synthase (AHAS) were mainly responsible for D. sophia resistance to tribenuron-methyl. In this study, D. sophia plant individually homozygous for specific AHAS mutation (Pro197Leu, Pro197His, Pro197Ser, Pro197Thr, Asp376Glu and Trp574Leu) were generated. In addition, the effects of resistance mutations on pigments, growths and competitiveness of susceptible (S) and resistant (R) plants of D. sophia were investigated. The results indicated the R plants carrying Pro197Leu or Pro197His or Asp376Glu or Trp574Leu displayed stronger competitiveness than S plants. The adverse effects on R plants aggravated with the increase of R plants proportion, which made the R plants against domination the weed community in absent of herbicide selection. Therefore, these resistance mutation have no obvious adverse effects on the pigments (chlorophyll a, chlorophyll b and carotenoid), relative growth rates (RGR), leaf area ratio (LAR) and net assimilation rate (NAR) of R plants.

Identification of a novel PSEN1 mutation (Leu232Pro) in a Korean patient with early-onset Alzheimer's disease and a family history of dementia.

Science.gov (United States)

Park, Jiyun; An, Seong Soo A; Giau, Vo Van; Shim, Kyuhwan; Youn, Young Chul; Bagyinszky, Eva; Kim, SangYun

2017-08-01

In the present study, a novel mutation in exon 7 of presenilin 1 (Leu232Pro) was discovered in a Korean patient with early-onset Alzheimer's disease, who represented memory decline at 37 years of age, followed by impairment in spatial activity and concentrations and personality changes. Imaging analyses with magnetic resonance scan showed diffuse atrophy in the frontoparietal regions. Targeted next generation sequencing and Sanger sequencing identified a heterozygous T to C transition at position 695 (c.695T>C) of in presenilin 1 gene (PSEN1), resulting in a novel missense mutation at codon 232 from leucine to proline (L232P). Several family members of the patient developed dementia, suggesting an autosomal dominant inheritance; however, we were unable to perform a segregation analysis to confirm this. Since the proline may play a role as a helix breaker, this mutation could significantly disturb the transmembrane helix domain-V of PSEN1 and perturb its protein functions. This hypothesis was supported by the results from the in silico analyses, predicted a major kink on this helix. Several leucine>proline substitutions in other PSEN1 transmembrane helices revealed aggressive AD phenotypes. Future functional studies would be needed to evaluate the pathogenicity of this mutation in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

gene polymorphism and its serum lev

Indian Academy of Sciences (India)

Navya

Association of Interleukin-10 (-1082 A>G, -819 C >T and -592 C >A) gene polymorphism and its ... Th2 induced component of anti-β cell immunity is mediated principally by IL-10 (Lee et al. ..... promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma. ... Bone Marrow Transplant 36, 1089-1095.

Determination of the frequency of polymorphisms in genes related to the genome stability maintenance of the population residing at Monte Alegre, PA (Brazil) municipality; Determinacao da frequencia de polimorfismos em genes relacionados a manutencao da estabilidade do genoma na populacao residente no municipio de Monte Alegre, PA

Energy Technology Data Exchange (ETDEWEB)

Hozumi, Cristiny Gomes

2010-07-01

The human exposure to ionizing radiation coming from natural sources is an inherent feature of human life on earth, for man and all living things have always been exposed to these sources. Ionizing radiation is a known genotoxic agent which can affect the genomic stability and genes related to DNA repair may play a role when they have committed certain polymorphism. This study aimed to analyze the frequency of polymorphisms (SNPs) in genes of DNA repair and cell cycle control: hOGG1 (Ser326Cys), XRCC3 (Thr241 Met) and p53 (Arg72Pro) in saliva samples from a population located Monte Alegre, state of Para were collected in August 2008 and 40 samples of men and 46 samples of women, adding a total of 86 samples. By RFLP was determined the frequency of homozygous genotypes and / or heterozygous for polymorphic genes. The I)OGG1 gene was 5% of the allele 326Cys, XRCC3 gene found about 21 % of the allele 241 Met and p53 gene showed 40.8% of the 72Pro allele. And the genotype frequencies of individuals for the three genes were 91.04%, 88.06% and 59.7% for homozygous wild genotype, 5.97%, 11.94% and 22.39% for heterozygote genotype and 2,99%, zero and 17:91% for homozygous polymorphic hOGG1 genes respectively, XRCC3, p53. These values are similar to those found in previous studies. The influence of these polymorphisms, which are involved in DNA repair and consequent genotoxicity induced by radiation depends on dose and exposure factors such as smoking, which is statistically a factor in public health surveillance in the region. This study gathered information and molecular epidemiology in Monte Alegre, that help to characterization of local population. (author)

Association of DPP4 Gene Polymorphisms with Type 2 Diabetes Mellitus in Malaysian Subjects.

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Radwan H Ahmed

Full Text Available Genetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4 gene may play a role in the etiology of type 2 diabetes mellitus (T2DM. This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV.Ten DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 controls. Of these, 71 metabolic syndrome (MetS subjects were excluded from subsequent analysis. The odds ratios (ORs and their 95% confidence interval (CIs were calculated using multiple logistic regression for the association between the SNPs of DPP4 and T2DM. In addition, the serum levels of sDPP-IV were investigated to evaluate the association of the SNPs of DPP4 with the sDPP-IV levels.Dominant, recessive, and additive genetic models were employed to test the association of DPP4 polymorphisms with T2DM, after adjusting for age, race, gender and BMI. The rs12617656 was associated with T2DM in Malaysian subjects in the recessive genetic model (OR = 1.98, p = 0.006, dominant model (OR = 1.95, p = 0.008, and additive model (OR = 1.63, p = 0.001. This association was more pronounced among Malaysian Indians, recessive (OR = 3.21, p = 0.019, dominant OR = 3.72, p = 0.003 and additive model (OR = 2.29, p = 0.0009. The additive genetic model showed that DPP4 rs4664443 and rs7633162 polymorphisms were associated with T2DM (OR = 1.53, p = 0.039, and (OR = 1.42, p = 0.020, respectively. In addition, the rs4664443 G>A polymorphism was associated with increased sDPP-IV levels (p = 0.042 in T2DM subjects.DPP4 polymorphisms were associated with T2DM in Malaysian subjects, and linked to variations in sDPP-IV levels. In addition, these associations were more pronounced among Malaysian Indian subjects.

Polymorphisms of the P-selectin gene and risk of myocardial infarction in men and women in the ECTIM extension study. Etude cas-temoin de l'infarctus myocarde.

Science.gov (United States)

Kee, F; Morrison, C; Evans, A E; McCrum, E; McMaster, D; Dallongeville, J; Nicaud, V; Poirier, O; Cambien, F

2000-11-01

Studies in animal models and humans implicate cell adhesion molecules in atherogenesis but their role in mediating the risk of myocardial infarction is unclear. The ECTIM (étude cas-temoin de l'infarctus myocarde) extension study was established to determine whether a previously implicated polymorphism of the P-selectin gene was associated with myocardial infarction risk in men and women in Belfast and Glasgow. PATIENTS AND STUDY SETTING: 696 cases with a recent myocardial infarction and 561 age matched controls (both male and female) were recruited into a case-control study in MONICA project areas of Belfast and Glasgow. Demographic and lifestyle information was collected by interview administered questionnaire, and each subject was examined and provided a blood sample for DNA extraction. The polymerase chain reaction (PCR) was used to amplify regions encompassing the P-selectin Thr-->Pro (A/C) polymorphism at position 715. Genotype odds ratios for myocardial infarction were estimated by logistic regression adjusted for population, age, and sex. There was no significant association between conventional risk factors (such as hypercholesterolaemia, increased body mass index, or raised blood pressure) and either the rare or the common Pro(715) allele of the P-selectin gene in controls. Overall, comparing Pro(715)/Pro(715) and Pro(715)/Thr(715) with Thr(715)/Thr(715), with adjustment for centre, age, and sex, the odds ratio was 0.78 (95% confidence interval 0.60 to 1.00) (p = 0.054), indicating a "protective" effect of the less common Pro(715) allele. There was no significant heterogeneity in odds ratios between men and women either in this sample or when combined with the original ECTIM subjects. In a large population based study in two regions of the UK, we have been able to corroborate the earlier ECTIM findings of a lower frequency of the Thr/Pro(715) polymorphism in subjects with myocardial infarction. An apparently "protective effect" of similar magnitude also

Gene-gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems in recurrent pregnancy loss.

Science.gov (United States)

Su, Mei-Tsz; Lin, Sheng-Hsiang; Chen, Yi-Chi; Kuo, Pao-Lin

2014-06-01

Both vascular endothelial growth factor A (VEGFA) and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) systems play major roles in angiogenesis. A body of evidence suggests VEGFs regulate critical processes during pregnancy and have been associated with recurrent pregnancy loss (RPL). However, little information is available regarding the interaction of these two major major angiogenesis-related systems in early human pregnancy. This study was conducted to investigate the association of gene polymorphisms and gene-gene interaction among genes in VEGFA and EG-VEGF systems and idiopathic RPL. A total of 98 women with history of idiopathic RPL and 142 controls were included, and 5 functional SNPs selected from VEGFA, KDR, EG-VEGF (PROK1), PROKR1 and PROKR2 were genotyped. We used multifactor dimensionality reduction (MDR) analysis to choose a best model and evaluate gene-gene interactions. Ingenuity pathways analysis (IPA) was introduced to explore possible complex interactions. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL (P<0.01). The MDR test revealed that the KDR (Q472H) polymorphism was the best loci to be associated with RPL (P=0.02). IPA revealed EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3 signaling pathways. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL. EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3.

Serotonin transporter (SERT gene polymorphism in Parkinson’s disease

Directory of Open Access Journals (Sweden)

Mahmut Özkaya

2004-06-01

Full Text Available Background: Parkinson disease (PD is the second most common neurodegenerative disorder with a prevalence of about 2% in persons older than 65 years of age. Neurodegenerative process in PD is not restricted to the dopaminergic neurons of the substantia nigra but also affects serotoninergic neurons. It has been shown that PD brains with Lewy bodies in the substantia nigra also had Lewy bodies in the raphe nuclei. The re-uptake of 5HT released into the synaptic cleft is mediated by the 5HT transporter (SERT. The SERT gene has been mapped to the chromosome of 17q11.1-q12 and has two main polymorphisms: intron two VNTR polymorphism and promoter region 44 bp insertion/deletion polymorphism. Objective: In this study we investigated whether two polymorphic regions in the serotonin transporter gene are associated with PD. Material and Method: After obtaining informed consent, blood samples were collected from 76 patients and 54 healthy volunteers. Genomic DNA was extracted from peripheral leucocytes using standard methods. The SERT gene genotypes were determined using polymerase chain reaction (PCR method. Results: Based on the intron 2 VNTR polymorphism of SERT gene, the distribution of 12/12, 12/10 and 10/10 genotypes were found as, 56.6 %, 35.5 %, 7.9 % in patients whereas this genotype distribution in control group was 40.7 %, 46.3 % and 13 %, respectively. According to 5-HTTLPR polymorphism, the distribution of L/L, L/S and S/S genotypes were found as 27.6 % 51.3 % and 21.1 % in patients whereas this genotype distribution in control group was 33.4 %, 50.0 % and 16.6 %, respectively. Despite the fact that the genotype distribution of SERT gene polymorphism in patients and control group seemed to be different from each other, this difference was not found to be statistically significant. Conclusion: This finding suggests that polymorphisms within the SERT gene do not play a major role in PD susceptibility in the Turkish population.

Association of -330 interleukin-2 gene polymorphism with oral cancer.

Science.gov (United States)

Singh, Prithvi Kumar; Kumar, Vijay; Ahmad, Mohammad Kaleem; Gupta, Rajni; Mahdi, Abbas Ali; Jain, Amita; Bogra, Jaishri; Chandra, Girish

2017-12-01

Cytokines play an important role in the development of cancer. Several single-nucleotide polymorphisms (SNPs) of cytokine genes have been reported to be associated with the development and severity of inflammatory diseases and cancer predisposition. This study was undertaken to evaluate a possible association of interleukin 2 (IL-2) (- 330A>C) gene polymorphisms with the susceptibility to oral cancer. The SNP in IL-2 (-330A>C) gene was genotyped in 300 oral cancer patients and in similar number of healthy volunteers by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the association of the gene with the disease was evaluated. IL-2 (-330A>C) gene polymorphism was significantly associated with oral cancer whereas it was neither associated with clinicopathological status nor with cancer pain. The AC heterozygous genotype was significantly associated with oral cancer patients as compared to controls [odds ratio (OR): 3.0; confidence interval (CI): 2.14-4.20; Poral cancer (OR: 1.80; CI: 1.39-2.33; PC) gene polymorphism was also associated with oral cancer in tobacco smokers and chewers. Our results showed that oral cancer patients had significantly higher frequency of AA genotype but significantly lower frequency of AC genotype and C allele compared to controls. The IL-2 AC genotype and C allele of IL-2 (-330A>C) gene polymorphisms could be potential protective factors and might reduce the risk of oral cancer in Indian population.

STAT4 gene polymorphism in patients after renal allograft transplantation.

Science.gov (United States)

Dąbrowska-Żamojcin, Ewa; Dziedziejko, Violetta; Safranow, Krzysztof; Domański, Leszek; Słuczanowska-Głabowska, Sylwia; Pawlik, Andrzej

2016-01-01

STAT4 (signal transducer and activator of transcription 4) is involved in the regulation of innate and adaptive immune responses. Some studies have suggested that STAT4 may be involved in the immune response after graft transplantation. Several polymorphisms in the STAT4 gene have been identified. The most commonly studied polymorphism in the STAT4 gene is rs7574865. In our study, we examined whether this polymorphism is associated with the early and late functions of renal allografts. A total of 270 recipients of first renal transplants were included in the study. Single nucleotide polymorphisms (SNPs) within the STAT4 gene were genotyped using TaqMan genotyping assays. There were no statistically significant associations between the STAT4 gene rs7574865 polymorphism and delayed graft function, acute rejection, chronic allograft dysfunction, post-transplant diabetes mellitus, or creatinine serum concentrations after transplantation. Our results suggest a lack of association between the STAT4 rs7574865 SNP and kidney allograft function in the Polish population.

Evaluation of inflammation-related genes polymorphisms in Mexican with Alzheimer’s disease: a pilot study

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Danira eToral-Rios

2015-05-01

Full Text Available Amyloid peptide is able to promote the activation of microglia and astrocytes in Alzheimer’s disease (AD, and this stimulates the production of pro-inflammatory cytokines. Inflammation contributes to the process of neurodegeneration and therefore is a key factor in the development of AD. Some of the most important proteins involved in AD inflammation are: clusterin (CLU, complement receptor 1 (CR1, C reactive protein (CRP, tumor necrosis factor α (TNF- α, the interleukins 1α (IL - 1α, 6 (IL-6, 10 (IL-10 and cyclooxygenase 2 (COX-2. In particular, COX-2 is encoded by the prostaglandin-endoperoxide synthase 2 gene (PTGS2. Since variations in the genes that encode these proteins may modify gene expression or function, it is important to investigate whether these variations may change the developing AD. The aim of this study was to determine whether the presence of polymorphisms in the genes encoding the aforementioned proteins is associated Mexican patients with AD. Fourteen polymorphisms were genotyped in 96 subjects with AD and the differences in allele, genotype and haplotype frequencies were analyzed. Additionally, an ancestry analysis was conducted to exclude differences in genetic ancestry among groups as a confounding factor in the study. Significant differences in frequencies between AD and controls were found for the SNP rs20417 within the PTGS2 gene. Ancestry analysis revealed no significant differences in the ancestry of the compared groups, and the association was significant even after adjustment for ancestry and correction for multiple testing, which strengthens the validity of the results. We conclude that this polymorphism plays an important role in the development of the AD pathology and further studies are required, including their proteins.

A novel polymorphism of resistin gene and its association with meat ...

African Journals Online (AJOL)

Searching for candidate gene polymorphisms and their relationship with meat quality traits is an important issue for Bos taurus industry. In this study, we evaluated polymorphism of resistin (RETN) gene involved in energy metabolism. Using the polymerase chain reaction-single strand conformation polymorphism ...

Functional analysis of four naturally occurring variants of human constitutive androstane receptor.

Science.gov (United States)

Ikeda, Shinobu; Kurose, Kouichi; Jinno, Hideto; Sai, Kimie; Ozawa, Shogo; Hasegawa, Ryuichi; Komamura, Kazuo; Kotake, Takeshi; Morishita, Hideki; Kamakura, Shiro; Kitakaze, Masafumi; Tomoike, Hitonobu; Tamura, Tomohide; Yamamoto, Noboru; Kunitoh, Hideo; Yamada, Yasuhide; Ohe, Yuichiro; Shimada, Yasuhiro; Shirao, Kuniaki; Kubota, Kaoru; Minami, Hironobu; Ohtsu, Atsushi; Yoshida, Teruhiko; Saijo, Nagahiro; Saito, Yoshiro; Sawada, Jun-ichi

2005-01-01

The human constitutive androstane receptor (CAR, NR1I3) is a member of the orphan nuclear receptor superfamily that plays an important role in the control of drug metabolism and disposition. In this study, we sequenced all the coding exons of the NR1I3 gene for 334 Japanese subjects. We identified three novel single nucleotide polymorphisms (SNPs) that induce non-synonymous alterations of amino acids (His246Arg, Leu308Pro, and Asn323Ser) residing in the ligand-binding domain of CAR, in addition to the Val133Gly variant, which was another CAR variant identified in our previous study. We performed functional analysis of these four naturally occurring CAR variants in COS-7 cells using a CYP3A4 promoter/enhancer reporter gene that includes the CAR responsive elements. The His246Arg variant caused marked reductions in both transactivation of the reporter gene and in the response to 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO), which is a human CAR-specific agonist. The transactivation ability of the Leu308Pro variant was also significantly decreased, but its responsiveness to CITCO was not abrogated. The transactivation ability and CITCO response of the Val133Gly and Asn323Ser variants did not change as compared to the wild-type CAR. These data suggest that the His246Arg and Leu308Pro variants, especially His246Arg, may influence the expression of drug-metabolizing enzymes and transporters that are transactivated by CAR.

The Serotonin Transporter Gene Polymorphisms and Risk of Ischemic Stroke

DEFF Research Database (Denmark)

Mortensen, Janne Kærgård; Kraglund, Kristian Lundsgaard; Johnsen, Søren Paaske

2018-01-01

may influence platelet activity, as they result in different levels of transporters and thereby different levels of serotonin in platelets. SERT gene polymorphisms have thus been associated with the risk of myocardial infarction. A similar association may exist between SERT gene polymorphisms...... and stroke. However, to our knowledge, this potential association has not previously been studied. We therefore aimed to investigate the association between polymorphisms in the SERT gene and the risk of ischemic stroke/transitory ischemic attack (TIA). MATERIALS AND METHODS: We conducted a case...

CYP1A1 and CYP1B1 in human lymphocytes as biomarker of exposure: effect of dioxin exposure and polymorphisms

Energy Technology Data Exchange (ETDEWEB)

Duursen, M. van; Sanderson, T.; Berg, M. van den [Inst. for Risk Assessment Sciences, Utrecht (Netherlands)

2004-09-15

There are several known genetic polymorphisms of the CYP1A1 and CYP1B1 genes. A polymorphism in the 3'-untranslated region of the CYP1A1 gene (CYP1A1 MspI or CYP1A1 m1) is often studied in relation with breast or lung cancer, but little is known about the functional effect of this polymorphism. An amino acid substitution in codon 432 (Val to Leu) of the CYP1B1 gene is associated with a lower catalytic activity of the enzyme. However, the involvement of these polymorphisms on the inducibility of CYP1A1 and CYP1B1 gene expression is unclear. CYP1A1 and CYP1B1 mRNA expression levels can be determined in peripheral blood lymphocytes. This makes them potential candidates for use as biomarker of exposure to environmental compounds. Interindividual variations in mRNA expression patterns, catalytic activity and polymorphisms are very important factors when CYP1A1 and CYP1B1 expression patterns are used as biomarker of exposure, but little is known about it. Spencer et al. showed a concentration-dependent increase of CYP1B1 mRNA in lymphocytes upon exposure in vitro to 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD), the most potent dioxin. Yet, only a few studies describe the in vivo correlation between polymorphisms, mRNA expression level and exposure to environmental factors. In this study, we wanted to obtain a better insight in the CYP1A1 and CYP1B1 mRNA expression and enzyme activity in human lymphocytes. We determined the constitutive CYP1A1 and CYP1B1 mRNA expression in lymphocytes of ten healthy volunteers and the variability in sensitivity toward enzyme induction by TCDD. Further, the CYP1A1 m1 and CYP1B1 Val432Leu polymorphisms were determined.

Highly significant association between two common single nucleotide polymorphisms in CORIN gene and preeclampsia in Caucasian women.

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Alain Stepanian

Full Text Available Preeclampsia is a frequent medical complication during pregnancy. Corin, a serine protease which activates pro-atrial natriuretic peptide, has recently been shown to be involved in the pathophysiology of preeclampsia. The aim of this study was to search for CORIN gene variations and their association to preeclampsia in Caucasian and African women. Our study population was composed of 571 pregnant women (295 with preeclampsia and 276 normotensive controls matched for maternal and gestational age, and ethnic origin. The 22 exons of the CORIN gene were sequenced in a discovery sample (n = 260, where 31 single nucleotide polymorphisms were identified. In a replication sample (n = 311, 4 single nucleotide polymorphisms were tested. Two minor alleles (C for rs2271036 and G for rs2271037 were significantly associated to preeclampsia. Adjusted odds ratios [95% confidence interval] were 2.5 [1.2-3.8] (p = 0.007 and 2.3 [1.5-3.5] (p = 1.3 × 10(-4, respectively. These associations were ethnic-specific, as only found in the Caucasian of subjects (odds ratio = 3.5 [1.8-6.6], p = 1.1 × 10(-4; odds ratio = 3.1 [1.7-5.8], p = 2.1 × 10(-4, for each single nucleotide polymorphism, respectively. The two single nucleotide polymorphisms are in almost perfect linkage disequilibrium (r(2 = 0.93. No specific association was found with severe preeclampsia, early-onset preeclampsia nor fetal growth retardation. In conclusion, this is the first report of a highly significant association between these two single nucleotide polymorphisms in CORIN gene and preeclampsia. Our findings further support the probability of a critical role of corin in preeclamspia pathophysiology at the uteroplacental interface.

Association of transforming growth factor-ß3 gene polymorphism ...

African Journals Online (AJOL)

Genotyping for the TGF-β3 gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and BslI restriction endonuclease showed a mutation in 294-bp fragment located on the fourth intron of chromosome 5. Polymorphism in TGF-β3 gene was significantly (P < 0.1) associated with ...

PPARγ Pro12Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes

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Jensen Majken K

2009-06-01

Full Text Available Abstract Background Acute coronary syndrome (ACS is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor γ (PPARγ plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim was to investigate if the polymorphism PPARγ2 Pro12Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPARγ activity, such as alcohol intake, smoking, and use of non-steroidal anti-inflammatory medicine. Methods A case-cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested within the population-based prospective study Diet, Cancer and Health of 57,053 individuals. Results Homozygous male variant allele carriers of PPARγ2 Pro12Ala were at higher risk of ACS (HR = 2.12, 95% CI: 1.00–4.48 than homozygous carriers of the Pro-allele. Among men, there was a statistically significant interaction between genotypes and alcohol intake such that homozygous variant allele carriers with a low alcohol intake were at higher risk of ACS (HR = 25.3, CI: 16.5–38.7 compared to homozygous common allele carriers (p for interaction Conclusion In the present study, there were no consistent associations between PPARγ Pro12Ala and risk of ACS, and no consistent interaction with alcohol, BMI, NSAID or smoking in relation to ACS.

The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

Science.gov (United States)

Ramos-Araque, Maria E; Rodriguez, Cristina; Vecino, Rebeca; Cortijo Garcia, Elisa; de Lera Alfonso, Mercedes; Sanchez Barba, Mercedes; Colàs-Campàs, Laura; Purroy, Francisco; Arenillas, Juan F; Almeida, Angeles; Delgado-Esteban, Maria

2018-04-23

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.

Association of Interleukin-27 gene rs153109 polymorphism and chronic hepatitis B infection

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Samira Mokhtari

2017-04-01

Full Text Available Background: According to World Health Organization (WHO report about 400 million people are chronically infected with hepatitis B virus (HBV. Host immune responses which are mainly controlled by cytokines, can be either effective in disease progression or control the infection. Interleukin-27 (IL-27 is a pro-inflammatory cytokine which promotes Th1 responses. Genetic variations (e.g. single nucleotide polymorphisms [SNPs] can affect the product or activity of IL-27 gene. The aim of present study was to determine the association between IL-27 rs153109 and chronic HBV infection among the Iranian population. Materials and Methods: In this study chronic HBV patients (n=120, Anti-HBc Ab positive and HBsAg positive for more than 6 months and controls (n=120 from healthy individuals referred to Tehran Taleghani hospital (2013-2014 were studied. Genotypes of IL-27 gene polymorphism were detected by PCR-RFLP. DNA sequencing was applied on 10% of samples to validate the genotyping results. The studied variables were polymorphism genotypes/alleles, clinical status, age and gender. Results: Results showed no statistically significant difference for patients and control groups neither in genotype frequencies of AA among the chronic group (30% compared to healthy controls (32.5% (P=0.368; nor in allele frequency A 60.4% for patients against A 59.2% in control groups (P=0.780. Conclusion: Despite the importance of IL-27 in the immune response, the findings of this study suggests that genetic variants of IL-27 SNP 153109A/G were not associated with susceptibility to the chronic infection of HBV.

Leu-9 (CD 7) positivity in acute leukemias: a marker of T-cell lineage?

Science.gov (United States)

Ben-Ezra, J; Winberg, C D; Wu, A; Rappaport, H

1987-01-01

Monoclonal antibody Leu-9 (CD 7) has been reported to be a sensitive and specific marker for T-cell lineage in leukemic processes, since it is positive in patients whose leukemic cells fail to express other T-cell antigens. To test whether Leu-9 is indeed specific for T-cell leukemias, we examined in detail 10 cases of acute leukemia in which reactions were positive for Leu-9 and negative for other T-cell-associated markers including T-11, Leu-1, T-3, and E-rosettes. Morphologically and cytochemically, 2 of these 10 leukemias were classified as lymphoblastic, 4 as myeloblastic, 2 as monoblastic, 1 as megakaryoblastic, and 1 as undifferentiated. The case of acute megakaryoblastic leukemia is the first reported case to be Leu-9 positive. None of the 10 were TdT positive. Of six cases (two monoblastic, one lymphoblastic, one myeloblastic, one megakaryoblastic, and one undifferentiated) in which we evaluated for DNA gene rearrangements, only one, a peroxidase-positive leukemia, showed a novel band on study of the T-cell-receptor beta-chain gene. We therefore conclude that Leu-9 is not a specific marker to T-cell lineage and that, in the absence of other supporting data, Leu-9 positivity should not be used as the sole basis of classifying an acute leukemia as being T-cell derived.

Assessment of MC1R and α-MSH gene sequences in Iranian vitiligo patients

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Eskandani M

2010-01-01

Full Text Available Background: Vitiligo is an acquired pigmentary disorder of the skin that is caused by unknown factors and is characterized by white and depigmented patches that enlarge and become more numerous with time. Genetic factors, oxidative stress, autoimmunity, and neurochemical agents, such as catecholamines might also contribute to vitiligo. Cutaneous pigmentation is determined by the amounts of eumelanin and pheomelanin synthesized by the epidermal melanocytes and interference of melanocortin-1 receptor (MC1R, a G-protein coupled receptor, its normal agonist, alpha-melanocyte stimulating hormone (α-MSH, and key enzymes, such as tyrosinase, to protect against sun-induced DNA damage. The MC1R, a 7 pass trans-membrane G-protein coupled receptor, is a key control point in melanogenesis. Loss-of-function mutations at the MC1R are associated with a switch from eumelanin to pheomelanin production, resulting in a red or yellow coat color. Aim: In this research, we aim to examine the genetic variety of MC1R and α-MSH gene in 20 Iranian vitiligo patients and 20 healthy controls. Materials and Methods: Analysis of the MC1R coding gene was performed with direct sequencing. Results: We found the following 9 MC1R coding region variants: Arg163Gl (G488A, Arg227Leu (G680A, Val 97Phe (G289T, Asp184Asn (G550A, Arg227Lys (G680A, Arg142His (G425A, Val60Leu (G178T, Val247Met (C739A, and Val174Ile (G520A. We also found 2 frameshift changes: one of them was the Insertion of C (frameshift in Pro136, stop at Trp148 and the other, Insertion of G (frameshift in Pro256, stop at Trp 333. Of all the changes, the most common was Val60Leu at 5% in patients vs 20% in controls, Val247Met at 15% in patients vs 0% in controls and Val174Ile at 15% in controls and 0% in patients. The other variants showed a frequency <5% in both patients and controls. Also in this study, we have examined the frequency of single nucleotide polymorphisms within the α-MSH genes with direct sequencing in

Do polymorphisms and haplotypes of mismatch repair genes modulate risk of sporadic colorectal cancer?

Czech Academy of Sciences Publication Activity Database

Tulupová, Elena; Kumar, R.; Hánová, Monika; Slyšková, Jana; Pardini, Barbara; Poláková, Veronika; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Halamková, J.; Hemminki, K.; Vodička, Pavel

2008-01-01

Roč. 648, 1-2 (2008), s. 40-45 ISSN 0027-5107 R&D Projects: GA ČR GA310/07/1430 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : DNA mismatch repair * Genetic polymorphism * Haplotype analysis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.198, year: 2008

Genetic variation in codons 167, 198 and 200 of the beta-tubulin gene in whipworms (Trichuris spp.) from a range of domestic animals and wildlife

DEFF Research Database (Denmark)

Hansen, Tina Vicky Alstrup; Nejsum, Peter; Olsen, Annette

2013-01-01

A recurrent problem in the control of whipworm (Trichuris spp.) infections in many animal species and man is the relatively low efficacy of treatment with a single application of benzimidazoles (BZs). The presence of single nucleotide polymorphisms (SNPs) in codons 167, 198 and 200 in the beta...

Do prion protein gene polymorphisms induce apoptosis in non ...

Indian Academy of Sciences (India)

2016-08-26

Aug 26, 2016 ... Genetic variations such as single nucleotide polymorphisms (SNPs) in prion protein coding gene, Prnp, greatly affect susceptibility to prion diseases in mammals. Here, the coding region of Prnp was screened for polymorphisms in redeared turtle, Trachemys scripta. Four polymorphisms, L203V, N205I, ...

Evaluation of glucose metabolism and reproductive hormones in polycystic ovary syndrome on the basis of peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala genotype.

Science.gov (United States)

Tok, E C; Aktas, A; Ertunc, D; Erdal, E M; Dilek, S

2005-06-01

Peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala polymorphism has been suggested as a protective factor for polycystic ovary syndrome (PCOS). In this study, we aimed to investigate metabolic features and reproductive hormones in women with PCOS and compare these features with control women on the basis of Pro12Ala genotype. This study involved 60 randomly selected women with PCOS and 60 controls. Main outcome measures were anthropometric measures, variables of glucose metabolism and reproductive hormones. All the patients were genotyped for Pro12Ala variant of PPAR-gamma2 gene. Patients with Pro12Ala polymorphism were more obese in both groups. Furthermore, they had lower fasting insulin levels, were less insulin-resistant and were less glucose-intolerant as demonstrated by 2 h glucose concentrations. However, there was no difference in reproductive hormone levels on the basis of Pro12Ala genotype. Both control women and women with PCOS had significant differences in glucose metabolism on the basis of PPAR-gamma2 Pro12Ala polymorphism. Pro12Ala variant may break the process that leads to PCOS in susceptible women, instead of being a direct causal relationship between Pro12Ala polymorphism and PCOS.

CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes.

Science.gov (United States)

Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L; Newman, Peter J

2016-02-11

Human platelet alloantigens (HPAs) reside on functionally important platelet membrane glycoproteins and are caused by single nucleotide polymorphisms in the genes that encode them. Antibodies that form against HPAs are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia and posttransfusion purpura. The HPA-1a/HPA-1b alloantigen system, also known as the Pl(A1)/Pl(A2) polymorphism, is the most frequently implicated HPA among whites, and a single Leu33Pro amino acid polymorphism within the integrin β3 subunit is responsible for generating the HPA-1a/HPA-1b alloantigenic epitopes. HPA-1b/b platelets, like those bearing other low-frequency platelet-specific alloantigens, are relatively rare in the population and difficult to obtain for purposes of transfusion therapy and diagnostic testing. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) gene-editing technology to transform Leu33 (+) megakaryocytelike DAMI cells and induced pluripotent stem cells (iPSCs) to the Pro33 allotype. CD41(+) megakaryocyte progenitors derived from these cells expressed the HPA-1b (Pl(A2)) alloantigenic epitope, as reported by diagnostic NciI restriction enzyme digestion, DNA sequencing, and western blot analysis using HPA-1b-specific human maternal alloantisera. Application of CRISPR/Cas9 technology to genetically edit this and other clinically-important HPAs holds great potential for production of designer platelets for diagnostic, investigative, and, ultimately, therapeutic use. © 2016 by The American Society of Hematology.

Polymorphism of the prolactin gene and its association with egg ...

African Journals Online (AJOL)

p2492989

In this study, polymorphism of the prolactin gene was screened in six Chinese native ... Prolactin (PRL) is a single-chain polypeptide hormone that belongs to the growth hormone gene ..... Enhance the efficiency of single-strand conformation polymorphism analysis by short polyacrylamide gel and modified silver staining.

Interethnic diversity of the CD209 (rs4804803 gene promoter polymorphism in African but not American sickle cell disease

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Jenelle A. Noble

2015-02-01

Full Text Available Elucidating the genomic diversity of CD209 gene promoter polymorphism could assist in clarifying disease pathophysiology as well as contribution to co-morbidities. CD209 gene promoter polymorphism has been shown to be associated with susceptibility to infection. We hypothesize that CD209 mutant variants occur at a higher frequency among Africans and in sickle cell disease. We analyzed the frequency of the CD209 gene (rs4804803 in healthy control and sickle cell disease (SCD populations and determined association with disease. Genomic DNA was extracted from blood samples collected from 145 SCD and 231 control Africans (from Mali, 331 SCD and 379 control African Americans and 159 Caucasians. Comparative analysis among and between groups was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. Per ethnic diversification, we found significant disparity in genotypic (23.4% versus 16.9% versus 3.2% and allelic frequencies (48.7% versus 42.1% versus 19.8% of the homozygote mutant variant of the CD209 (snp 309A/G gene promoter between Africans, African Americans and Caucasians respectively. Comparative evaluation between disease and control groups reveal a significant difference in genotypic (10.4% versus 23.4%; p = 0.002 and allelic frequencies (39.7% versus 48.7%; p = 0.02 of the homozygote mutant variant in African SCD and healthy controls respectively, an observation that is completely absent among Americans. Comparing disease groups, we found no difference in the genotypic (p = 0.19 or allelic (p = 0.72 frequencies of CD209 homozygote mutant variant between Africans and Americans with sickle cell disease. The higher frequency of CD209 homozygote mutant variants in the African control group reveals a potential impairment of the capacity to mount an immune response to infectious diseases, and possibly delineate susceptibility to or severity of infectious co-morbidities within and between groups.

Association between p53 codon 72 polymorphism and systemic lupus erythematosus

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Mohammad Nabavi

2014-06-01

Full Text Available Aim : Systemic lupus erythematosus (SLE is a systemic vasculitic disorder, with multiple genes involved in the disease pathogenesis. The p53 gene plays an important role in controlling the cell cycle. We aimed to study the prevalence of p53 polymorphism in SLE patients and analyze the relationship between the p53 polymorphism and clinical-laboratory features of the disease. Material and methods : This case-control study was conducted on patients with confirmed SLE at Namazi Hospital, Shiraz, Iran. Seventy-seven patients with SLE including 9 (11.8% men and 68 (88.2% women with mean age of 25.61 ±10.69 years and 80 healthy controls with mean age of 51.82 ±14.25 years were included. The patients’ information, including the epidemiological profile, disease history, disease symptoms and also the laboratory findings, were extracted from the hospital records. The p53 expression was determined in lyzed lymphocytes. The data were analyzed using SPSS software version 14.00 for Windows considering p < 0.05 as statistically significant. Results : The frequencies of Arg/Arg, Pro/Pro and Arg/Pro among normal controls were 38.8%, 28.8% and 37.5%, respectively, but in the patients, Arg/Arg, Pro/Pro and Arg/Pro genotypes frequencies were shown to be 29.2%, 12.3% and 58.5%, respectively. Thus, heterozygous form of this polymorphism was shown to be associated with the disease more than the homozygous alleles. There was a significant relationship between the different allele types of p53 and some clinical features of SLE. There was no association between the different allele types and any of the initial manifestations of the disease and the laboratory findings, as well. Conclusions: In an Iranian population the functional oncoprotein of p53 with codon 72 polymorphism may play an important role in the pathogenesis and clinical presentation of SLE.

Polymorphism at codon 36 of the p53 gene.

Science.gov (United States)

Felix, C A; Brown, D L; Mitsudomi, T; Ikagaki, N; Wong, A; Wasserman, R; Womer, R B; Biegel, J A

1994-01-01

A polymorphism at codon 36 in exon 4 of the p53 gene was identified by single strand conformation polymorphism (SSCP) analysis and direct sequencing of genomic DNA PCR products. The polymorphic allele, present in the heterozygous state in genomic DNAs of four of 100 individuals (4%), changes the codon 36 CCG to CCA, eliminates a FinI restriction site and creates a BccI site. Including this polymorphism there are four known polymorphisms in the p53 coding sequence.

A single nucleotide polymorphism in the zona pellucida 3 gene is associated with the first parity litter size in Hu sheep.

Science.gov (United States)

Chong, Yuqing; Huang, Huarong; Liu, Guiqiong; Jiang, Xunping; Rong, Weiheng

2018-03-31

Zona pellucida 3 (ZP3) is a primary sperm receptor and acrosome reaction inducer. As a candidate gene, the ZP3 gene has been widely studied since it has great influence on reproductive traits in farm animals. However, little is known about the association between polymorphisms of the coding region of the ZP3 gene and the first parity litter size in Hu sheep. Therefore, the objective of this study was to identify single nucleotide polymorphisms (SNPs) of the ZP3 gene associated with the first parity litter size in Hu sheep. A total of 462 female Hu sheep were sampled to detect SNPs in the coding region of the ZP3 gene. Six SNPs were identified and the reliability of all estimated allele frequencies reached 0.9545 except for one locus (g.2293C > T). SNP (rs401271989) was identified as that involved in amino acid change (Ile → Leu). This amino acid was located at the beginning of a β-strand and outside of the ZP3 protein membrane, and it was most likely to be a ligand-binding site (the possibility was 0.917). At this locus, individuals with AC genotype had a larger litter size than those with CC genotype in the first parity (2.050 vs 1.727, p size in Hu sheep, and it may affect the function of ZP3 protein by impacting the secondary and tertiary protein structures. The present study demonstrates that SNP (rs401271989) could be used in marker-assisted selection of the first parity litter size in Hu sheep. Copyright © 2018 Elsevier B.V. All rights reserved.

STAT4 gene polymorphism in patients after renal allograft transplantation

OpenAIRE

D?browska-?amojcin, Ewa; Dziedziejko, Violetta; Safranow, Krzysztof; Doma?ski, Leszek; S?uczanowska-G?abowska, Sylwia; Pawlik, Andrzej

2016-01-01

Introduction STAT4 (signal transducer and activator of transcription 4) is involved in the regulation of innate and adaptive immune responses. Some studies have suggested that STAT4 may be involved in the immune response after graft transplantation. Several polymorphisms in the STAT4 gene have been identified. The most commonly studied polymorphism in the STAT4 gene is rs7574865. In our study, we examined whether this polymorphism is associated with the early and late functions of renal allog...

Association between Ghrelin gene (GHRL polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients

Directory of Open Access Journals (Sweden)

Yang Yongfeng

2012-02-01

Full Text Available Abstract Background Ghrelin (GHRL is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG is a common side effect of the atypical antipsychotics (AAPs used to treat schizophrenia (SZ. Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI. However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response. Methods Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C were genotyped in 634 schizophrenia patients and 606 control subjects. Results There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05. There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS. However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P P Conclusions These four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.

Association between ghrelin gene (GHRL) polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients.

Science.gov (United States)

Yang, Yongfeng; Li, Wenqiang; Zhao, Jingyuan; Zhang, Hongxing; Song, Xueqin; Xiao, Bo; Yang, Ge; Jiang, Chengdi; Zhang, Dai; Yue, Weihua; Lv, Luxian

2012-02-28

Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response. Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects. There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.

Identification for the First Time of Cyclo(d-Pro-l-Leu Produced by Bacillus amyloliquefaciens Y1 as a Nematocide for Control of Meloidogyne incognita

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Qaiser Jamal

2017-10-01

Full Text Available The aim of the current study was to describe the role and mechanism of Bacillus amyloliquefaciens Y1 against the root-knot nematode, Meloidogyne incognita, under in vitro and in vivo conditions. Initially, the exposure of the bacterial culture supernatant and crude extract of Y1 to M. incognita significantly inhibited the hatching of eggs and caused the mortality of second-stage juveniles (J2, with these inhibitory effects depending on the length of incubation time and concentration of the treatment. The dipeptide cyclo(d-Pro-l-Leu was identified in B. amyloliquefaciens culture for the first time using chromatographic techniques and nuclear magnetic resonance (NMR 1H, 13C, H-H COSY, HSQC, and HMBC and recognized to have nematocidal activity. Various concentrations of cyclo(d-Pro-l-Leu were investigated for their effect on the hatching of eggs and J2 mortality. Moreover, the in vivo nematocidal activity of the Y1 strain was investigated by conducting pot experiments in which tomato plants were inoculated with M. incognita. Each and every pot was amended 50 mL of fertilizer media (F, or Y1 culture, or nematicide (N (only once, or fertilizer media with N (FN at 1, 2, 3, 4 and 5 weeks after transplantation. The results of the pot experiments demonstrated the antagonistic effect of B. amyloliquefaciens Y1 against M. incognita as it significantly decreases the count of eggs and galls per root of the tomato plant as well as the population of J2 in the soil. Besides, the investigation into the growth parameters, such as the length of shoot, shoot fresh and dry weights of the tomato plants, showed that they were significantly higher in the Y1 strain Y1-treated plants compared to F-, FN- and N-treated plants. Therefore, the biocontrol repertoire of this bacterium opens a new insight into the applications in crop pest control.

PPAR gamma Pro(12)Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes

DEFF Research Database (Denmark)

Vogel, Ulla Birgitte; Segel, Stine; Dethlefsen, Claus

2009-01-01

Background: Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim...... was to investigate if the polymorphism PPAR gamma 2 Pro(12)Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPAR gamma activity, such as alcohol intake, smoking, and use of non...

Depressive symptoms in schizophrenia and dopamine and serotonin gene polymorphisms.

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Peitl, Vjekoslav; Štefanović, Mario; Karlović, Dalibor

2017-07-03

Although depressive symptoms seem to be frequent in schizophrenia they have received significantly less attention than other symptom domains. As impaired serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis of depression and schizophrenia this study sought to investigate the putative association between several functional gene polymorphisms (SERT 5-HTTLPR, MAO-A VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this study were to closely examine schizophrenia symptom domains by performing factor analysis of the two most used instruments in this setting (Positive and negative syndrome scale - PANSS and Calgary depression rating scale - CDSS) and to examine the influence of investigated gene polymorphisms on the schizophrenia symptom domains, focusing on depressive scores. A total of 591 participants were included in the study (300 schizophrenic patients and 291 healthy volunteers). 192 (64%) of schizophrenic patients had significant depressive symptoms. Genotype distribution revealed no significant differences regarding all investigated polymorphisms except the separate gender analysis for MAO-A gene polymorphism which revealed significantly more allele 3 carriers in schizophrenic males. Factor analysis of the PANSS scale revealed the existence of five separate factors (symptom domains), while the CDSS scale revealed two distinct factors. Several investigated gene polymorphisms (mostly SERT and MAO-A, but also COMT) significantly influenced two factors from the PANSS (aggressive/impulsive and negative symptoms) and one from the CDSS scale (suicidality), respectively. Depressive symptoms in schizophrenic patients may be influenced by functional gene polymorphisms, especially those implicated in serotonergic neurotransmission. Copyright © 2017 Elsevier Inc. All rights reserved.

Association of ACE Gene I/D polymorphism with migraine in Kashmiri population.

Science.gov (United States)

Wani, Irfan Yousuf; Sheikh, Saleem; Shah, Zafar Amin; Pandith, Arshid A; Wani, Mushtaq; Asimi, Ravouf; Wani, Maqbool; Sheikh, Shahnawaz; Mehraj, Iqra

2016-01-01

Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region. The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP). Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene. We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine.

[C677T polymorphism of the methylentetrahydrofolate reductase gene in mothers of children affected with neural tube defects].

Science.gov (United States)

Morales de Machín, Alisandra; Méndez, Karile; Solís, Ernesto; Borjas de Borjas, Lisbeth; Bracho, Ana; Hernández, María Luisa; Negrón, Aimara; Delgado, Wilmer; Sánchez, Yanira

2015-09-01

Neural tube defects (NTD) are the most common congenital anomalies of the central nervous system, with a multifactorial pattern of inheritance, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene 677C>T polymorphism has been implicated as a risk factor for NTD. The main objective of this research was to investigate the association of the 677C>T polymorphism of the MTHFR gene as a genetic risk factor for NTD. Molecular analysis was performed in DNA samples from 52 mothers with antecedent of NTD offspring and from 119 healthy control mothers. Using the Polymerase Chain Reaction, a 198 bases pairs fragment was digested with the restriction enzyme Hinfi. 677T MTHFR allele frequencies for the problem and the control groups were 51.92% and 34.45%, respectively, and 677C MTHFR allele frequencies were 48.08% and 65.55%, respectively. There were significant differences in allele (p: 0.002) and genotype (p: 0.007) frequencies between these two groups. The odds ratio (OR) to the TT genotype vs. the CC genotype was estimated as OR: 4.9 [95% CI: 1,347-6.416] p: 0.002; CT+TT vs. CC: OR: 2.9 [95% CI: 1.347-6.416] p: 0.005; TT vs. CT+CC: OR: 2.675 [95% CI: 1,111-6.441] p: 0.024. The data presented in this study support the relationship between MTHFR 677C>T polymorphism and risk in mothers with antecedent of NTD offspring.

The Evaluation of IL6 and ESR1 Gene Polymorphisms in Primary Dysmenorrhea.

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Ozsoy, Asker Zeki; Karakus, Nevin; Yigit, Serbulent; Cakmak, Bulent; Nacar, Mehmet Can; Yılmaz Dogru, Hatice

2016-01-01

Primary dysmenorrhea is the most common gynecological complaint with painful menstrual cramps in pelvis without any pathology. It affects about half of menstruating women, and it causes significant disruption in quality of life. We investigated the association between IL6 gene promoter and ESR1 gene XbaI and PvuII polymorphisms and primary dysmenorrhea. In this case-control study, 152 unrelated young women with primary dysmenorrhea and 150 unrelated healthy age-matched controls participated. Genomic DNA was isolated and IL6 and ESR1 gene polymorphisms were genotyped using PCR-based RFLP assay. The distribution of genotype and allele frequencies of IL6 gene promoter and ESR1 gene XbaI polymorphisms were not statistically different between patients and controls (p > 0.05). However, the genotype and allele frequencies of ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls (p = 0.009 and p = 0.021, respectively). Statistically significant associations were also observed between age and married status of primary dysmenorrhea patients and ESR1 gene PvuII polymorphism (p = 0.044 and p = 0.023, respectively). In combined genotype analyses, AG at ESR1 XbaI and TC at ESR1 PvuII loci encoded a p-value of 0.027. Thus, individuals who are heterozygote at both loci have a lower risk of developing primary dysmenorrhea. Our study suggests no strong association between IL6 gene promoter and ESR1 gene XbaI polymorphisms and primary dysmenorrhea in Turkish women. However, ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls. The potential association between ESR1 gene PvuII polymorphism and age and married status of dysmenorrhea patients deserves further consideration.

Glucocorticoid receptor gene polymorphism and juvenile idiopathic arthritis

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Scheplyagina Larisa A

2011-01-01

Full Text Available Abstract Background The glucocorticoid receptor gene (NR3C1 has been suggested as a candidate gene affecting juvenile idiopathic arthritis (JIA course and prognosis. The purpose of this study is to investigate the glucocorticoid receptor gene BclI polymorphism (rs41423247 in JIA patients, the gene's role in susceptibility to juvenile idiopathic arthritis, and its associations with JIA activity, course and bone mineralization. Methods One hundred twenty-two Caucasian children with JIA and 143 healthy ethnically matched controls were studied. We checked markers of clinical and laboratory activity: morning stiffness, Ritchie Articular Index (RAI, swollen joint count (SJC, tender joint count (TJC, physician's visual analog scale (VAS, hemoglobin level (Hb, leukocyte count (L, platelet count (Pl, Westergren erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, albumin, DAS and DAS28. Bone mineralization was measured by dual-energy X-ray absorptiometry (DXA of lumbar spine L1-L4. Assessments of bone metabolism included osteocalcin, C-terminal telopeptide (CTT, parathyroid hormone (PTH, total and ionized calcium, inorganic phosphate and total alkaline phosphatase (TAP. BclI polymorphism was genotyped by polymerase chain reaction restriction fragment length polymorphism. Results No association was observed between glucocorticoid receptor gene polymorphism and the presence or absence of JIA. In girls with JIA, the presence of the G allele was associated with an unfavorable arthritis course, a younger age of onset of arthritis (p = 0.0017, and higher inflammatory activity. The higher inflammatory activity was demonstrated by the following: increased time of morning stiffness (p = 0.02, VAS (p = 0.014, RAI (p = 0.048, DAS (p = 0.035, DAS28 (p = 0.05, Pl (p = 0.003, L (p = 0.046, CRP (p = 0.01. In addition, these patients had bone metabolism disturbances as follows: decreased BA (p = 0.0001, BMC (p = 0.00007, BMD (0.005 and Z score (p = 0.002; and

LuFLA1PRO and LuBGAL1PRO promote gene expression in the phloem fibres of flax (Linum usitatissimum).

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Hobson, Neil; Deyholos, Michael K

2013-04-01

Cell type-specific promoters were identified that drive gene expression in an industrially important product. To identify flax (Linum usitatissimum) gene promoters, we analyzed the genomic regions upstream of a fasciclin-like arabinogalactan protein (LuFLA1) and a beta-galactosidase (LuBGAL1). Both of these genes encode transcripts that have been found to be highly enriched in tissues bearing phloem fibres. Using a beta-glucuronidase (GUS) reporter construct, we found that a 908-bp genomic sequence upstream of LuFLA1 (LuFLA1PRO) directed GUS expression with high specificity to phloem fibres undergoing secondary cell wall development. The DNA sequence upstream of LuBGAL1 (LuBGAL1PRO) likewise produced GUS staining in phloem fibres with developing secondary walls, as well as in tissues of developing flowers and seed bolls. These data provide further evidence of a specific role for LuFLA1 in phloem fibre development, and demonstrate the utility of LuFLA1PRO and LuBGAL1PRO as tools for biotechnology and further investigations of phloem fibre development.

DNA Characterization and Polymorphism of KISS1 Gene in Egyptian ...

African Journals Online (AJOL)

The objective of this study was the detection of the restriction fragment length polymorphism (RFLP) and single nucleotide polymorphisms (SNPs) of KISS1 gene in six major Egyptian small ruminant breeds. The primers used in this study flanked a 377 bp fragment from intron 1 of KISS1 gene in sheep and goat. These PCR ...

Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T], A Second and Third Case Described in Two Unrelated Dutch Families

NARCIS (Netherlands)

Pondman, Kirsten M.; Brinkman, Jacoline W.; van der Straaten, Hanneke M.; Stroobants, An K.; Harteveld, Cornelis L.

2018-01-01

We report two families, members of which are carriers of a hemoglobin (Hb) variant previously described as Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T; p.Pro115Leu]. In the first family of Dutch origin, the proband, a 32-year-old male and his 65-year-old father, were both carriers of Hb

Using RNA-Seq for gene identification, polymorphism detection and transcript profiling in two alfalfa genotypes with divergent cell wall composition in stems

Science.gov (United States)

2011-01-01

Background Alfalfa, [Medicago sativa (L.) sativa], a widely-grown perennial forage has potential for development as a cellulosic ethanol feedstock. However, the genomics of alfalfa, a non-model species, is still in its infancy. The recent advent of RNA-Seq, a massively parallel sequencing method for transcriptome analysis, provides an opportunity to expand the identification of alfalfa genes and polymorphisms, and conduct in-depth transcript profiling. Results Cell walls in stems of alfalfa genotype 708 have higher cellulose and lower lignin concentrations compared to cell walls in stems of genotype 773. Using the Illumina GA-II platform, a total of 198,861,304 expression sequence tags (ESTs, 76 bp in length) were generated from cDNA libraries derived from elongating stem (ES) and post-elongation stem (PES) internodes of 708 and 773. In addition, 341,984 ESTs were generated from ES and PES internodes of genotype 773 using the GS FLX Titanium platform. The first alfalfa (Medicago sativa) gene index (MSGI 1.0) was assembled using the Sanger ESTs available from GenBank, the GS FLX Titanium EST sequences, and the de novo assembled Illumina sequences. MSGI 1.0 contains 124,025 unique sequences including 22,729 tentative consensus sequences (TCs), 22,315 singletons and 78,981 pseudo-singletons. We identified a total of 1,294 simple sequence repeats (SSR) among the sequences in MSGI 1.0. In addition, a total of 10,826 single nucleotide polymorphisms (SNPs) were predicted between the two genotypes. Out of 55 SNPs randomly selected for experimental validation, 47 (85%) were polymorphic between the two genotypes. We also identified numerous allelic variations within each genotype. Digital gene expression analysis identified numerous candidate genes that may play a role in stem development as well as candidate genes that may contribute to the differences in cell wall composition in stems of the two genotypes. Conclusions Our results demonstrate that RNA-Seq can be

Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression

DEFF Research Database (Denmark)

Koefoed, Pernille; Woldbye, David P. D.; Hansen, Thomas v. O.

2012-01-01

Objective: There is clear evidence of a genetic component in major depression, and several studies indicate that neuropeptide Y (NPY) could play an important role in the pathophysiology of the disease. A well-known polymorphism encoding the substitution of leucine to proline in the signal peptide...... sequence of NPY (Leu7Pro variation) was previously found to protect against depression. Our study aimed at replicating this association in a large Danish population with major depression. Method: Leu7Pro was studied in a sample of depressed patients and ethnically matched controls, as well as psychiatric...... disease controls with schizophrenia. Possible functional consequences of Leu7Pro were explored in vitro. Results: In contrast to previous studies, Pro7 appeared to be a risk allele for depression, being significantly more frequent in the depression sample (5.5 n = 593; p = 0.009; odds ratio, OR: 1...

Genetic polymorphisms within tumor necrosis factor gene promoter region: a role for susceptibility to ventilator-associated pneumonia.

Science.gov (United States)

Kotsaki, Antigoni; Raftogiannis, Maria; Routsi, Christina; Baziaka, Fotini; Kotanidou, Anastasia; Antonopoulou, Anastasia; Orfanos, Stylianos E; Katsenos, Chrisostomos; Koutoukas, Pantelis; Plachouras, Diamantis; Mandragos, Konstantinos; Giamarellos-Bourboulis, Evangelos J

2012-08-01

Debatable findings exist among various studies regarding the impact of single nucleotide polymorphisms (SNPs) within the promoter region of the tumor necrosis factor (TNF) gene for susceptibility to infections. Their impact was investigated in a cohort of mechanically ventilated patients who developed ventilator-associated pneumonia (VAP). Two-hundred and thirteen mechanically ventilated patients who developed VAP were enrolled. Genomic DNA was extracted and SNPs at the -376, -308 and -238 position of the promoter region of the TNF gene were assessed by restriction fragment length polymorphisms. Monocytes were isolated from 47 patients when they developed sepsis and stimulated by bacterial endotoxin for the production of TNFα and of interleukin-6 (IL-6). Patients were divided into two groups; 166 patients bearing only wild-type alleles of all three studied polymorphisms; and 47 patients carrying at least one A allele of the three studied SNPs. Time between start of mechanical ventilation and advent of VAP was significantly shorter in the second group than in the first group (log-rank: 4.416, p: 0.041). When VAP supervened, disease severity did not differ between groups. Stimulation of TNFα and of IL-6 was much greater by monocytes for patients carrying A alleles. Carriage of at least one A allele of the three studied SNPs at the promoter region of the TNF-gene is associated with shorter time to development of VAP but it is not associated with disease severity. Findings may be related with a role of the studied SNPs in the production of pro-inflammatory cytokines. Copyright © 2012 Elsevier Ltd. All rights reserved.

CYP3A4*18: it is not rare allele in Japanese population.

Science.gov (United States)

Yamamoto, Takehito; Nagafuchi, Nobue; Ozeki, Takeshi; Kubota, Takahiro; Ishikawa, Hiroshi; Ogawa, Seishi; Yamada, Yasuhiko; Hirai, Hisamaru; Iga, Tatsuji

2003-01-01

We sequenced all 13 exons of the CYP3A4 gene derived from 48 Japanese subjects. One subject possess the 20070 T>C mutation in the exon 10 (result in leu293Pro substitution, namely CYP3A4(*)18), as heterozygote. Thus, we investigated the frequency of CYP3A4(*)18 in 118 Japanese population using polymerase chain reaction-restriction fragment length polymorphism with Msp I and determined that the frequency of the CYP3A4(*)18 allele was 1.3%.

Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes.

Science.gov (United States)

Wiersma, Anje C; Leegwater, Peter Aj; van Oost, Bernard A; Ollier, William E; Dukes-McEwan, Joanna

2007-10-19

Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. alpha-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan delta, titin cap, alpha-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies.

New polymorphisms of Xeroderma Pigmentosum DNA repair genes in myelodysplastic syndrome.

Science.gov (United States)

Santiago, Sabrina Pinheiro; Junior, Howard Lopes Ribeiro; de Sousa, Juliana Cordeiro; de Paula Borges, Daniela; de Oliveira, Roberta Taiane Germano; Farias, Izabelle Rocha; Costa, Marília Braga; Maia, Allan Rodrigo Soares; da Nóbrega Ito, Mayumi; Magalhães, Silvia Maria Meira; Pinheiro, Ronald Feitosa

2017-07-01

The association between Xeroderma Pigmentosum DNA repair genes (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) polymorphisms and myelodysplastic syndrome (MDS) have not been reported. To assess the functional role between these polymorphisms and MDS, we evaluated 189 samples stratified in two groups: 95 bone marrow samples from MDS patients and 94 from healthy elderly volunteers used as controls. Genotypes for all polymorphisms were identified in DNA samples in an allelic discrimination experiment by real-time polymerase chain reaction (qPCR). We also studied the mRNA expression of XPA and XPC genes to evaluate if its polymorphisms were functional in 53 RNAm MDS patients by qPCR methodologies. To the rs2228000 polymorphism, the CT and TT polymorphic genotype were associated with increased odds ratio (OR) of more profound cytopenia (hemoglobin and neutrophils count). To the rs1799793 polymorphism, we found that the GG homozygous wild-type genotype was associated with a decreased chance of developing MDS. We observed low expression of XPA in younger patients, in hypoplastic MDS and patients with abnormal karyotype when presented AG or AA polymorphic genotypes. We also found that there was a statistically significant interaction between the presence of micromegakaryocyte on down regulation of XPC regarding the CT heterozygous genotype of the rs1800975 polymorphism. Our results suggest that new functional polymorphisms of Xeroderma Pigmentosum DNA repair genes in MDS are related to its pathogenesis and prognosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polymorphisms at the Ligand Binding Site of the Vitamin D Receptor Gene and Osteomalacia

Science.gov (United States)

Ak, Duygu Gezen; Kahraman, Hakkí; Dursun, Erdinç; Duman, Belgin Süsleyici; Erensoy, Nevin; Alagöl, Faruk; Tanakol, Refik; Yılmazer, Selma

2005-01-01

Vitamin D receptor (VDR) gene polymorphisms have been suggested as possible determinants of bone mineral density (BMD) and calcium metabolism. In this study, our aim was to determine whether there is an association between VDR gene polymorphism and osteomalacia or not. We determined ApaI and TaqI polymorphisms in the vitamin D receptor gene in 24 patients with osteomalacia and 25 age-matched healthy controls. Serum calcium, phosphorus, ALP, PTH, 25OHD levels were also examined. We used PCR and RFLP methods to test for an association between osteomalacia and polymorphisms within, intron 8 and exon 9 of the VDR gene. When the control and patients were compared for their ApaI and TaqI genotypes there was no relationship between VDR gene allelic polymorphisms and osteomalacia. Whereas a nearly significant difference for A allele was found in the allellic distribution of the patients (p = 0.08). Also no association between biochemical data and VDR gene polymorphisms was observed. PMID:16403954

Polymorphisms at the Ligand Binding Site of the Vitamin D Receptor Gene and Osteomalacia

Directory of Open Access Journals (Sweden)

Duygu Gezen Ak

2005-01-01

Full Text Available Vitamin D receptor (VDR gene polymorphisms have been suggested as possible determinants of bone mineral density (BMD and calcium metabolism. In this study, our aim was to determine whether there is an association between VDR gene polymorphism and osteomalacia or not. We determined ApaI and TaqI polymorphisms in the vitamin D receptor gene in 24 patients with osteomalacia and 25 age-matched healthy controls. Serum calcium, phosphorus, ALP, PTH, 25OHD levels were also examined. We used PCR and RFLP methods to test for an association between osteomalacia and polymorphisms within, intron 8 and exon 9 of the VDR gene. When the control and patients were compared for their ApaI and TaqI genotypes there was no relationship between VDR gene allelic polymorphisms and osteomalacia. Whereas a nearly significant difference for A allele was found in the allellic distribution of the patients (p = 0.08. Also no association between biochemical data and VDR gene polymorphisms was observed.

Genetic association between ghrelin polymorphisms and Alzheimer's disease in a Japanese population.

Science.gov (United States)

Shibata, Nobuto; Ohnuma, Tohru; Kuerban, Bolati; Komatsu, Miwa; Arai, Heii

2011-01-01

Ghrelin has been reported to enter the hippocampus and to bind to the neurons of the hippocampal formation. This peptide also affects neuronal glucose uptake and decreases tau hyperphosphorylation. There is increasing evidence suggesting an association between ghrelin and Alzheimer's disease (AD) pathology. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) of the ghrelin gene are associated with AD. The SNPs were genotyped using TaqMan technology and were analyzed using a case-control study design. Our case-control dataset consisted of 182 AD patients and 143 age-matched controls. Hardy-Weinberg equilibrium and linkage disequilibrium analyses suggest that the region in and around the gene is highly polymorphic. One SNP, rs4684677 (Leu90Gln), showed a marginal association with age of AD onset. We did not detect any association between the other SNPs of the ghrelin gene and AD. There have been few genetic studies on the relationship between circulating ghrelin and functional SNPs. Further multifactorial studies are needed to clarify the relationship between ghrelin and AD. Copyright © 2011 S. Karger AG, Basel.

Genetic polymorphism of toll-like receptors 4 gene by polymerase chain reaction-restriction fragment length polymorphisms, polymerase chain reaction-single-strand conformational polymorphism to correlate with mastitic cows

Directory of Open Access Journals (Sweden)

Pooja H. Gupta

2015-05-01

Full Text Available Aim: An attempt has been made to study the toll-like receptors 4 (TLR4 gene polymorphism from cattle DNA to correlate with mastitis cows. Materials and Methods: In present investigation, two fragments of TLR4 gene named T4CRBR1 and T4CRBR2 of a 316 bp and 382 bp were amplified by polymerase chain reaction (PCR, respectively from Kankrej (22 and Triple cross (24 cattle. The genetic polymorphisms in the two populations were detected by a single-strand conformational polymorphism in the first locus and by digesting the fragments with restriction endonuclease Alu I in the second one. Results: Results showed that both alleles (A and B of two loci were found in all the two populations and the value of polymorphism information content indicated that these were highly polymorphic. Statistical results of χ2 test indicated that two polymorphism sites in the two populations fit with Hardy–Weinberg equilibrium (p˂0.05. Meanwhile, the effect of polymorphism of TLR4 gene on the somatic cell score (SCS indicated the cattle with allele a in T4CRBR1 showed lower SCS than that of allele B (p<0.05. Thus, the allele A might play an important role in mastitis resistance in cows. Conclusion: The relationship between the bovine mastitis trait and the polymorphism of TLR4 gene indicated that the bovine TLR4 gene may play an important role in mastitis resistance.

Are Toll-like receptor gene polymorphisms associated with prostate cancer?

International Nuclear Information System (INIS)

Kutikhin, Anton G; Yuzhalin, Arseniy E

2012-01-01

The suggestion that there is a connection between chronic intraprostatic inflammation and prostate cancer was declared some years ago. As Toll-like receptors (TLRs) are the key players in the processes of chronic intraprostatic inflammation, there is a hypothesis that TLR gene polymorphisms may be associated with prostate cancer risk. Although a number of comprehensive studies have been conducted on large samples in various countries, reliable connections between these single nucleotide polymorphisms and prostate cancer risk, stage, grade, aggressiveness, ability to metastasize, and mortality have not been detected. Results have also varied slightly in different populations. The data obtained regarding the absence of connection between the polymorphisms of the genes encoding interleukin-1 receptor-associated kinases (IRAK1 and IRAK4) and prostate cancer risk might indicate a lack of association between inherited variation in the TLR signaling pathway and prostate cancer risk. It is possible to consider that polymorphisms of genes encoding TLRs and proteins of the TLR pathway also do not play a major role in the etiology and pathogenesis of prostate cancer. Feasibly, it would be better to focus research on associations between TLR single nucleotide polymorphisms and cancer risk in other infection-related cancer types

Cytokine gene polymorphisms and their association with cervical ...

African Journals Online (AJOL)

Materials and methods: The present study was undertaken to evaluate association of cytokine gene polymorphisms with cervical cancer in a north Indian population. Genotyping of single nucleotide polymorphisms (SNPs) viz. IL 6-597G/A (rs1800797), IL-1b-511C/T (rs16944) and TNF-a-308G/A (rs1800629) was carried out ...

MTHFR Gene C677T Polymorphism in Autism Spectrum Disorders

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Elif Funda Sener

2014-01-01

Full Text Available Aim. Autism is a subgroup of autism spectrum disorders, classified as a heterogeneous neurodevelopmental disorder and symptoms occur in the first three years of life. The etiology of autism is largely unknown, but it has been accepted that genetic and environmental factors may both be responsible for the disease. Recent studies have revealed that the genes involved in the folate/homocysteine pathway may be risk factors for autistic children. In particular, C677T polymorphism in the MTHFR gene as a possible risk factor for autism is still controversial. We aimed to investigate the possible effect of C677T polymorphism in a Turkish cohort. Methods. Autism patients were diagnosed by child psychiatrists according to DSM-IV and DSM-V criteria. A total of 98 children diagnosed as autistic and 70 age and sex-matched children who are nonautistic were tested for C677T polymorphism. This polymorphism was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP methods. Results. MTHFR 677T-allele frequency was found to be higher in autistic children compared with nonautistic children (29% versus 24%, but it was not found statistically significant. Conclusions. We conclude that other MTHFR polymorphisms such as A1298C or other folate/homocysteine pathway genes may be studied to show their possible role in autism.

Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes

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van Oost Bernard A

2007-10-01

Full Text Available Abstract Background Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. Results We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. α-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan δ, titin cap, α-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. Conclusion The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies.

Androgen Receptor Gene Polymorphism, Aggression, and Reproduction in Tanzanian Foragers and Pastoralists

Science.gov (United States)

Butovskaya, Marina L.; Lazebny, Oleg E.; Vasilyev, Vasiliy A.; Dronova, Daria A.; Karelin, Dmitri V.; Mabulla, Audax Z. P.; Shibalev, Dmitri V.; Shackelford, Todd K.; Fink, Bernhard; Ryskov, Alexey P.

2015-01-01

The androgen receptor (AR) gene polymorphism in humans is linked to aggression and may also be linked to reproduction. Here we report associations between AR gene polymorphism and aggression and reproduction in two small-scale societies in northern Tanzania (Africa)—the Hadza (monogamous foragers) and the Datoga (polygynous pastoralists). We secured self-reports of aggression and assessed genetic polymorphism of the number of CAG repeats for the AR gene for 210 Hadza men and 229 Datoga men (aged 17–70 years). We conducted structural equation modeling to identify links between AR gene polymorphism, aggression, and number of children born, and included age and ethnicity as covariates. Fewer AR CAG repeats predicted greater aggression, and Datoga men reported more aggression than did Hadza men. In addition, aggression mediated the identified negative relationship between CAG repeats and number of children born. PMID:26291982

Two methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, schizophrenia and bipolar disorder

DEFF Research Database (Denmark)

Jönsson, Erik G; Larsson, Kristina; Vares, Maria

2008-01-01

disorder. In a replication attempt the MTHFR C677T and A1298C SNPs were analyzed in three Scandinavian schizophrenia case-control samples. In addition, Norwegian patients with bipolar disorder were investigated. There were no statistically significant allele or genotype case-control differences....... The present Scandinavian results do not verify previous associations between the putative functional MTHFR gene polymorphisms and schizophrenia or bipolar disorder. However, when combined with previous studies in meta-analyses there is still evidence for association between the MTHFR C677T polymorphism......Recent meta-analyses of the methylenetetrahydrofolate reductase gene (MTHFR) have suggested association between two of its functional single gene polymorphisms (SNPs; C677T and A1298C) and schizophrenia. Studies have also suggested association between MTHFR C677T and A1298C variation and bipolar...

IDENTIFICATION OF GH|ALUI AND GHR|ALUI GENES POLYMORPHISMS IN INDONESIAN BUFFALO

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E. Andreas

2014-10-01

Full Text Available Growth hormone (GH is an anabolic hormone which sintesized and secreted by somatrotop cell inpituitary anterior lobe. GH exert its effect on growth and metabolism by interacting with a specificreceptor on the surface of the target cells. Growth hormone receptor (GHR has been suggested ascandidate gene for traits related to meat production in Bovidae. The objectives of this study were toidentify polymorphism of GH and GHR genes in buffalo. The 452 DNA samples buffalo were collectedfrom five populations in Indonesia (Siborong-Borong-Medan (65, Lebak-Banten (29, Pandeglang-Banten (180, Semarang-Central Java, and Mataram-West Nusa Tenggara (103. A gene fragment of theGH|AluI gene at 432 bp located on exon 3 and GHR|AluI gene at 298 bp on exon 10 were successfullyamplified by using the techniques of a PCR (polymerase chain reaction and genotyped by PCR-RFLP(restriction fragment length polymorphism then -SSCP (single strand conformation polymorphism. Theresults showed no polymorphisms were detected in these genes. All buffaloes tested had LL genotype forlocus GH|AluI and AA genotype for locus GHR|AluI.

Association of genetic polymorphism in GH gene with milk ...

Indian Academy of Sciences (India)

Associations were analysed between polymorphisms of the growth hormone gene (GH-MspI) (localized in intron 3) and milk production traits of Beijing Holstein cows (a total of 543 cows). Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method was used for identification of various ...

Impact of estrogen receptor α gene and oxytocin receptor gene polymorphisms on female sexuality

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Anastasia K Armeni

2017-02-01

Full Text Available Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA gene polymorphism (rs2234693-PvuII (T→C substitution and oxytocin receptor gene polymorphism (rs53576 (G→A substitution with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20–25 years of age, sexually active, with normal menstrual cycles (28–35 days, were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs, polycystic ovary syndrome (PCOS, thyroid diseases as well as drugs that are implicated in hypothalamus–pituitary–gonadal axis. T allele (wildtype of rs2234693 (PvuII polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic of rs53576 (OXTR polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII and A allele of rs53576 (OXTR polymorphisms (T + A group was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences.

Genetic Polymorphisms in Cytokine Genes in Colombian Patients with Ocular Toxoplasmosis.

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Naranjo-Galvis, C A; de-la-Torre, A; Mantilla-Muriel, L E; Beltrán-Angarita, L; Elcoroaristizabal-Martín, X; McLeod, R; Alliey-Rodriguez, N; Begeman, I J; López de Mesa, C; Gómez-Marín, J E; Sepúlveda-Arias, J C

2018-04-01

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii , which has the capacity to infect all warm-blooded animals worldwide. Toxoplasmosis is a major cause of visual defects in the Colombian population; however, the association between genetic polymorphisms in cytokine genes and susceptibility to ocular toxoplasmosis has not been studied in this population. This work evaluates the associations between polymorphisms in genes coding for the cytokines tumor necrosis factor alpha (TNF-α) (rs1799964, rs1800629, rs1799724, rs1800630, and rs361525), interleukin 1β (IL-1β) (rs16944, rs1143634, and rs1143627), IL-1α (rs1800587), gamma interferon (IFN-γ) (rs2430561), and IL-10 (rs1800896 and rs1800871) and the presence of ocular toxoplasmosis (OT) in a sample of a Colombian population (61 patients with OT and 116 healthy controls). Genotyping was performed with the "dideoxynucleotide (ddNTP) primer extension" technique. Functional-effect predictions of single nucleotide polymorphisms (SNPs) were done by using FuncPred. A polymorphism in the IL-10 gene promoter (-1082G/A) was significantly more prevalent in OT patients than in controls ( P = 1.93e-08; odds ratio [OR] = 5.27e+03; 95% confidence interval [CI] = 3.18 to 8.739; Bonferroni correction [BONF] = 3.48e-07). In contrast, haplotype "AG" of the IL-10 gene promoter polymorphisms (rs1800896 and rs1800871) was present at a lower frequency in OT patients ( P = 7e-04; OR = 0.10; 95% CI = 0.03 to 0.35). The +874A/T polymorphism of IFN-γ was associated with OT ( P = 3.37e-05; OR = 4.2; 95% CI = 2.478 to 7.12; BONF = 6.07e-04). Haplotype "GAG" of the IL-1β gene promoter polymorphisms (rs1143634, rs1143627, and rs16944) appeared to be significantly associated with OT ( P = 0.0494). The IL-10, IFN-γ, and IL-1β polymorphisms influence the development of OT in the Colombian population. Copyright © 2018 American Society for Microbiology.

Association between Single Nucleotide Polymorphisms in Vitamin D Receptor Gene Polymorphisms and Permanent Tooth Caries Susceptibility to Permanent Tooth Caries in Chinese Adolescent

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Miao Yu

2017-01-01

Full Text Available Purpose. Dental caries is a multifactorial infectious disease. In this study, we investigated whether single nucleotide polymorphisms (SNPs in vitamin D receptor (VDR gene were associated with susceptibility to permanent tooth caries in Chinese adolescents. Method. A total of 200 dental caries patients and 200 healthy controls aged 12 years were genotyped for VDR gene polymorphisms using the PCR-restriction fragment length polymorphism (PCR-RFLP assay. All of them were examined for their oral and dental status with the WHO criteria, and clinical information such as the Decayed Missing Filled Teeth Index (DMFT was evaluated. Genomic DNA was extracted from the buccal epithelial cells. The four polymorphic SNPs (Bsm I, Taq I, Apa I, and Fok I in VDR were assessed for both genotypic and phenotypic susceptibilities. Results. Among the four examined VDR gene polymorphisms, the increased frequency of the CT and CC genotype of the Fok I VDR gene polymorphism was associated with dental caries in 12-year-old adolescent, compared with the controls (X2 = 17.813, p≤0.001. Moreover, Fok I polymorphic allele C frequency was significantly increased in the dental caries cases, compared to the controls (X2 = 14.144, p≤0.001, OR = 1.730, 95% CI = 1.299–2.303. However, the other three VDR gene polymorphisms (Bsm I, Taq I, and Apa I showed no statistically significant differences in the caries groups compared with the controls. Conclusion. VDR-Fok I gene polymorphisms may be associated with susceptibility to permanent tooth caries in Chinese adolescent.

Polymorphism of growth hormone gene and its association with ...

African Journals Online (AJOL)

sunny t

2016-04-06

Apr 6, 2016 ... recorded to be more frequent (83.3, 92.86 and 90%) than pattern II (16.7, 7.14 and 10%) in Barki,. Rahmani ... Key words: Sheep, wool, growth hormone (GH) gene, polymorphism, single strand conformation polymorphism. (SSCP). ... electrophoresis and chemical and ribonuclease cleavage,. SSCP has ...

Paraoxonase-1 genetic polymorphisms and susceptibility to DNA damage in workers occupationally exposed to organophosphate pesticides

International Nuclear Information System (INIS)

Singh, Satyender; Kumar, Vivek; Thakur, Sachin; Banerjee, Basu Dev; Rautela, Rajender Singh; Grover, Shyam Sunder; Rawat, Devendra Singh; Pasha, Syed Tazeen; Jain, Sudhir Kumar; Ichhpujani, Rattan Lal; Rai, Arvind

2011-01-01

Human paraoxonase 1 (PON1) is a lipoprotein-associated enzyme involved in the detoxification of organophosphate pesticides (OPs) by hydrolyzing the bioactive oxons. Polymorphisms of the PON1 gene are responsible for variation in the expression and catalytic activity of PON1 enzyme. In the present study, we have determined (a) the prevalence of two common PON1 polymorphisms, (b) the activity of PON1 and acetylcholinesterase enzymes, and (c) the influence of PON1 genotypes and phenotypes variation on DNA damage in workers exposed to OPs. We examined 230 subjects including 115 workers exposed to OPs and an equal number of normal healthy controls. The results revealed that PON1 activity toward paraoxon (179.19 ± 39.36 vs. 241.52 ± 42.32 nmol/min/ml in controls) and phenylacetate (112.74 ± 17.37 vs. 134.28 ± 25.49 μmol/min/ml in controls) was significantly lower in workers than in control subjects (p 192 QR (Gln/Arg) and PON1 55 LM (Leu/Met) in workers and control subjects (p > 0.05). The PON1 activity toward paraoxonase was found to be significantly higher in the R/R (Arg/Arg) genotypes than Q/R (Gln/Arg) and lowest in Q/Q (Gln/Gln) genotypes in both workers and control subjects (p 55 LM (Leu/Met), PON1 activity toward paraoxonase was observed to be higher in individuals with L/L (Leu/Leu) genotypes and lowest in individuals with M/M (Met/Met) genotypes in both groups (p < 0.001). No influence of PON1 genotypes and phenotypes was seen on the activity of acetylcholinesterase and arylesterase. The DNA damage was observed to be significantly higher in workers than in control subjects (p < 0.05). Further, the individuals who showed least paraoxonase activity i.e., those with (Q/Q [Gln/Gln] and M/M [Met/Met]) genotypes showed significantly higher DNA damage compared to other isoforms in workers exposed to OPs (p < 0.05). The results indicate that the individuals with PON1 Q/Q and M/M genotypes are more susceptible toward genotoxicity. In conclusion, the study suggests

The evaluation of angiotensin-converting enzyme (ACE) gene I/D and IL-4 gene intron 3 VNTR polymorphisms in coronary artery disease.

Science.gov (United States)

Basol, Nursah; Celik, Atac; Karakus, Nevin; Ozturk, Sibel Demir; Ozsoy, Sibel Demir; Yigit, Serbulent

2014-01-01

Genetic polymorphism is a strong risk factor for coronary artery disease (CAD). In the present study, our aim was to evaluate angiotensin-converting enzyme (ACE) gene I/D polymorphism and interleukin-4 (IL-4) gene Intron 3 variable number of tandem repeat (VNTR) polymorphism in CAD. One hundred and twenty-four CAD patients and one hundred and twenty-three controls were enrolled. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses. The risk associated with inheriting the combined genotypes for the two polymorphisms were evaluated and it was found that the individuals who were P2P2-homozygous at IL-4 gene intron 3 VNTR and DD-homozygous at ACE gene I/D have a higher risk of developing CAD. Although, there is no correlation between IL4 VNTR polymorphism and ACE gene polymorphism and CAD, there is a strong association between CAD and co-existence of IL-4 VNTR and ACE gene polymorphisms in the Turkish population. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Association of TAP Gene Polymorphisms and Risk of Cervical Intraepithelial Neoplasia

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Camilla Natter

2013-01-01

Full Text Available Background. Transporter associated with antigen processing (TAP is responsible for peptide loading onto class I major histocompatibility complex (MHC-I molecules. TAP seems to facilitate the detection of HPV by MHC-I molecules and contributes to successful eradication of HPV. TAP polymorphisms could have an important impact on the course of HPV infection. Objective. The aim of this study is to evaluate the association between five TAP gene polymorphisms and the risk of CIN. Methods. This case-control study investigated five common TAP polymorphisms in TAP1 (1341 and 2254 and TAP2 (1135, 1693, and 1993 in 616 women with CIN and 206 controls. Associations between gene polymorphisms and risk of CIN were analysed by univariate and multivariable models. The combined effect of the five TAP gene polymorphisms on the risk for CIN was investigated by haplotype analysis. Results. No significant difference in genotype distribution of the five TAP polymorphisms was observed in women with CIN and controls. Haplotype analysis revealed that women with haplotype mut-wt-wt-wt-wt (TAP polymorphisms t1135-t1341-t1693-t1993-t2254 had a significantly lower risk for CIN, compared to women with the haplotype wt-wt-wt-wt-wt (; OR 0.5 []. Conclusion. Identification of this haplotype combination could be used to identify women, less susceptible for development of CIN following HPV infection.

Association of MTHFR and PPARγ2 gene polymorphisms in relation to type 2 diabetes mellitus cases among north Indian population.

Science.gov (United States)

Raza, Syed Tasleem; Abbas, Shania; Ahmed, Faisal; Fatima, Jalees; Zaidi, Zeashan Haider; Mahdi, Farzana

2012-12-15

Type 2 diabetes mellitus is a multifactorial and polygenic disease, which is considered as a major life threatening problem all over the world. There has been a worldwide effort in the identification of susceptibility genes for type 2 diabetes mellitus and its complications. At present, adequate data is not available dealing with MTHFR (rs1801133) and PPARγ2 (rs1801282) gene polymorphisms and its association with type 2 diabetes mellitus cases among north Indian populations. Thus, we conceived the need for further studies to investigate MTHFR and PPARγ2 gene polymorphisms and their susceptibility to type 2 diabetes mellitus in north Indian population. In this study, a total 175 subjects including 87 type 2 diabetes mellitus cases and 88 controls were enrolled. MTHFR and PPARγ2 gene polymorphisms in the cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The MTHFR gene CC, CT, TT genotype frequencies obtained were 40%, 43%, and 17% in type 2 diabetes mellitus cases and 56%, 29%, and 15% in healthy controls respectively. The OR for CC was 0.54 (95%CI 0.29-0.98, P=0.041, χ(2)=4.18, power=0.98), for CT 1.76 (95%CI 0.94-3.30, P=0.07, χ(2)=3.2, power=0.96), and for TT 1.2 (95%CI 0.53-2.70, P=0.66, χ(2)=0.198, power=0.76). The PPARγ2 gene GG CG, CC genotype frequencies obtained were 28%, 41%, and 31% in cases and 40%, 39%, and 21% in healthy controls respectively. OR for GG was 0.58 (95%CI 0.30-1.09, P=0.08, χ(2)=2.9, power=0.96), for CG 1.12 (95%CI 0.61-2.05, P=0.71, χ(2)=0.137, power=0.778), and for CC 1.63 (95%CI 0.82-3.23, P=0.156, χ(2)=2.01, power=0.92). It might be recommended that MTHFR CC genotype seems to be a good marker for the early identification of population at risk of type 2 diabetes mellitus. While we have detected significant difference in allelic frequencies of PPARγ2 C (Proline) and G (Alanine), but at genotypic level significant difference was not detected in this case

PPARgamma-2 and ADRB3 polymorphisms in connective tissue diseases and lipid disorders

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Grygiel-Górniak B

2018-03-01

Full Text Available Bogna Grygiel-Górniak,1 Iwona Ziółkowska-Suchanek,2 Elżbieta Kaczmarek,3 Maria Mosor,2 Jerzy Nowak,2 Mariusz Puszczewicz1 1Department of Rheumatology and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland; 2Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland; 3Department of Bioinformatics and Computational Biology, Poznan University of Medical Sciences, Poznan, Poland Background: The aim of the research genetic study was to investigate the association between variants (C1431T and Pro12Ala of the peroxisome proliferator-activated receptor (PPARgamma-2 gene, Trp64Arg polymorphism of the beta-3-adrenergic receptor gene and lipid profile in Polish population including group of 103 patients with connective tissue disease (CTD and 103 sex- and age-matched controls in context of statin use. Methods: Anthropometric and biochemical parameters were measured by routine methods, followed by genotyping (TagMan® Genotyping Assays, PCR-restriction fragment length polymorphism analysis. Nearly 30% of CTD patients used statins and 10% of the control group. Results: Although there were no differences between alleles and genotypes prevalence between CTD vs control groups, interesting lipid-gene associations were noted in this study. A higher level of triglycerides (TAG and TAG/high-density lipoprotein (HDL ratios was observed in CTD patients compared to controls. Similar differences were noted in CTD and control groups without statin treatment. Atherogenic markers: the atherogenic index of plasma, TAG/HDL and low-density lipoprotein/HDL ratio were low in the analyzed groups. Of the six analyzed polymorphisms, the Pro12Pro or C14131C or Trp64Trp genotypes were related to higher TAG and TAG/HDL ratios in patients with CTD; however, the highest TAG values were observed in the presence of the Trp64Trp genotype. Conclusion: Lipid disorders were present in both groups independent of statin treatment (mixed dyslipidemia and

Endothelial nitric oxide synthase gene Glu298Asp polymorphism ...

African Journals Online (AJOL)

Administrator

2011-09-12

Sep 12, 2011 ... Figure 1. The Glu298Asp polymorphism of eNOS gene was shown by .... mechanisms by which eNOS Asp298 polymorphism ... Asp298 is exposed to selective proteolytic cleavage in ... grounds, inclusion and exclusion criteria for PE women ... attention to meta analysis study, it is more probable that.

Evaluation of p53 Polymorphism in Patients with Pannus-Derived Prosthetic Dysfunction.

Science.gov (United States)

Gursoy, Mustafa Ozan; Karakoyun, Suleyman; Kalcik, Macit; Yesin, Mahmut; Gunduz, Sabahattin; Astarcioğlu, Mehmet Ali; Oğuz, Ali Emrah; Ozkan, Mehmet

2015-09-01

Prosthetic valve dysfunction (PVD) due to pannus formation is considered to occur due to a bioreaction to prosthetic material. The p53 gene plays a critical role in apoptosis and cell proliferation. p53 Arg72Pro polymorphism has been found to be associated with coronary stent restenosis, but has not yet been studied in prosthetic heart valve dysfunction. The study aim was to evaluate the association between pannus-derived PVD and p53 G72C(Arg72Pro) polymorphism. This single-center, prospective study included 25 patients (20 females, five males; mean age 45.6 +/- 12.5 years; group 1) who underwent redo valve surgery due to PVD, and 49 age- and gender-matched control patients (44 females, five males; mean age 47.3 +/- 12.2 years; group 2) with normofunctional prostheses. The prostheses were examined using transthoracic and transesophageal echocardiography. Analyses of p53 G72C(Arg72Pro) polymorphism were performed using Roche LightCyler 2.0 Real-time polymerase chain reaction. The most common location of replaced valves was the mitral position in both groups (88% and 89.8%, respectively). In group 1, normal alleles (GG) were observed in 12 patients (48%), while one patient (4%) showed a homozygous mutation (GC) and 12 patients (48%) showed a heterozygous mutation (CC). In group 2, 21 patients (42.9%) had normal alleles (GG), while four (8.2%) had a homozygous mutation (CC) and 24 (48.9%) had a heterozygous mutation (GC). No significant difference was observed between the groups with regards to p53 Arg72Pro polymorphism (p = 0.769). In patients with prosthetic valves, the underlying mechanism behind pannus formation is unrelated to p53 Arg72Pro polymorphism.

Leu452His mutation in lipoprotein lipase gene transfer associated with hypertriglyceridemia in mice in vivo.

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Kaiyue Sun

Full Text Available Mutated mouse lipoprotein lipase (LPL containing a leucine (L to histidine (H substitution at position 452 was transferred into mouse liver by hydrodynamics-based gene delivery (HD. Mutated-LPL (MLPL gene transfer significantly increased the concentrations of plasma MLPL and triglyceride (TG but significantly decreased the activity of plasma LPL. Moreover, the gene transfer caused adiposis hepatica and significantly increased TG content in mouse liver. To understand the effects of MLPL gene transfer on energy metabolism, we investigated the expression of key functional genes related to energy metabolism in the liver, epididymal fat, and leg muscles. The mRNA contents of hormone-sensitive lipase (HSL, adipose triglyceride lipase (ATGL, fatty acid-binding protein (FABP, and uncoupling protein (UCP were found to be significantly reduced. Furthermore, we investigated the mechanism by which MLPL gene transfer affected fat deposition in the liver, fat tissue, and muscle. The gene expression and protein levels of forkhead Box O3 (FOXO3, AMP-activated protein kinase (AMPK, and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α were found to be remarkably decreased in the liver, fat and muscle. These results suggest that the Leu452His mutation caused LPL dysfunction and gene transfer of MLPL in vivo produced resistance to the AMPK/PGC-1α signaling pathway in mice.

General and Specific Genetic Polymorphism of Cytokines-Related Gene in AITD

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Chen Xiaoheng

2017-01-01

Full Text Available Autoimmune thyroid disease (AITD shows the highest incidence among organ-specific autoimmune diseases and is the most common thyroid disease in humans, including Graves’ disease (GD and Hashimoto’s thyroiditis (HT. The susceptibility to autoimmune diseases is affected by increased autoantibody levels, susceptibility gene polymorphisms, environmental factors, and psychological factors, but the pathogenesis remains unclear. Various cytokines and related genes encoding them play important roles in the development and progression of AITD. CD152, an expression product of the CTLA-4 gene, downregulates T cell activation. The A/A genotype polymorphism in the CT60 locus may reduce the production of thyroid autoantibodies. The C1858T polymorphism of the PTNP22 gene reduces the expression of its encoded LYP, which increases the risk of GD and HT. GD is an organ-specific autoimmune disease involving increased secretion of thyroid hormone, whereas HT may be associated with the destruction of thyroid gland tissue and hypothyroidism. These two diseases exhibit similar pathogenesis but opposite trends in the clinical manifestations. In this review, we focus on the structure and function of these cytokines and related genes in AITD, as well as the association of polymorphisms with susceptibility to GD and HT, and attempt to describe their differences in pathogenesis and clinical manifestations.

PTH Gene Polymorphism and Breast Cancer Risk in Kazakhstan

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Nurgul Sikhayeva

2014-12-01

Full Text Available Introduction. Breast cancer is the most common type of cancer among women. In Kazakhstan, breast cancer holds first place among causes of women death caused by cancer in the 45-55 year age group . Many studies have shown that the risk of acquiring breast cancer may be related to the level of calcium in the blood serum. One of the important regulators of calcium metabolism in the body is the parathyroid hormone. Single nucleotide polymorphisms in the gene encoding the parathyroid hormone (PTH are associated with breast cancer development risk, and may modify the associative interaction between the levels of calcium intake and breast cancer. Experimental studies have shown that PTH gene has a carcinogenic effect. At least three studies showed a weak positive correlation between the risk of acquiring breast cancer and primary hyperparathyroidism, a state with high levels of PTH and often high levels of calcium. The aim of this investigation was to evaluate potential association between PTH gene polymorphism and breast cancer risk among Kazakhstani women.Methods. Female breast cancer patients (n = 429 and matched control women (n = 373 were recruited into a case – control study,. Genomic DNA was extracted from peripheral venous blood of study participants using Wizard® Genomic DNA Purification Kit (Promega, USA. Detection of PTH gene polymorphism (rs1459015 was done by means of the TaqMan® SNP Genotyping Assay of real-time PCR. Statistical analysis was conducted using SPSS 19.0.Results. PTH gene alleles were in Hardy–Weinberg equilibrium (p > 0.05. Distribution was 59% CC, 35% CT, 6% TT in the group with breast cancer and 50% CC, 43% CT, 6% TT in the control group. Total difference (between the group with breast cancer and the control group in allele frequencies for PTH polymorphism was not significant (p > 0.05. No association was found between rs1459015 TT and breast cancer risk (OR = 1.039; 95%, CI 0.740 - 1.297; p = 0.893.Conclusion. We

Malassezia Yeast and Cytokine Gene Polymorphism in Atopic Dermatitis.

Science.gov (United States)

Jain, Charu; Das, Shukla; Ramachandran, V G; Saha, Rumpa; Bhattacharya, S N; Dar, Sajad

2017-03-01

Atopic Dermatitis (AD) is a recurrent chronic condition associated with microorganism and their interaction with the susceptible host. Malassezia yeast is a known commensal which is thought to provoke the recurrent episodes of symptoms in atopic dermatitis patients. Malassezia immunomodulatory properties along with defective skin barrier in such host, results in disease manifestation. Here, we studied Single Nucleotide Polymorphism (SNP) in IL10 and IFN γ genes of the host and its relation with susceptibility to Malassezia infection. To isolate Malassezia yeast from AD patients and compare the genetic susceptibility of the host by correlating the cytokine gene polymorphism with the control subjects. Study was conducted from January 2012 to January 2013. It was a prospective observational study done in Department of Microbiology and Department of Dermatology and Venereology in University College of Medical Sciences and GTB Hospital, Delhi. Sample size comprised of 38 cases each of AD. Skin scrapings were used for fungal culture on Sabouraud Dextrose Agar (SDA) and Modified Dixon Agar (MDA) and isolated were identified as per conventional phenotypic methods. Genomic DNA was extracted from blood samples collected from all study subjects. Cytokine genotyping was carried out by Amplification Refractory Mutations System- Polymerase Chain Reaction (ARMS-PCR) with sequence specific primers. Three SNPs (IL10-1082A/G; IL10-819/592C/T; IFN-γ+874A/T) in two cytokine genes were assessed in all the patients and healthy controls. Chi-Square Test or Fisher's-Exact Test and Bonferroni's correction. In AD group, Malassezia yeasts were cultured in 24 out of 38 samples and thus the identification rate was 63.1 percent as compared to healthy group, 52.6 percent (20/38). Significant difference in allele, or genotype distribution were observed in IL10-819/592C/T and IFN-γ+874A/T gene polymorphism in AD group. Higher isolation rate in cases as compared to control group highlights the

Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

Science.gov (United States)

Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

2016-12-01

Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

Polymorphism in ABC transporter genes of Dirofilaria immitis

Directory of Open Access Journals (Sweden)

Thangadurai Mani

2017-08-01

Full Text Available Dirofilaria immitis, a filarial nematode, causes dirofilariasis in dogs, cats and occasionally in humans. Prevention of the disease has been mainly by monthly use of the macrocyclic lactone (ML endectocides during the mosquito transmission season. Recently, ML resistance has been confirmed in D. immitis and therefore, there is a need to find new classes of anthelmintics. One of the mechanisms associated with ML resistance in nematodes has been the possible role of ATP binding cassette (ABC transporters in reducing drug concentrations at receptor sites. ABC transporters, mainly from sub-families B, C and G, may contribute to multidrug resistance (MDR by active efflux of drugs out of the cell. Gene products of ABC transporters may thus serve as the targets for agents that may modulate susceptibility to drugs, by inhibiting drug transport. ABC transporters are believed to be involved in a variety of physiological functions critical to the parasite, such as sterol transport, and therefore may also serve as the target for drugs that can act as anthelmintics on their own. Knowledge of polymorphism in these ABC transporter genes in nematode parasites could provide useful information for the process of drug design. We have identified 15 ABC transporter genes from sub-families A, B, C and G, in D. immitis, by comparative genomic approaches and analyzed them for polymorphism. Whole genome sequencing data from four ML susceptible (SUS and four loss of efficacy (LOE pooled populations were used for single nucleotide polymorphism (SNP genotyping. Out of 231 SNPs identified in those 15 ABC transporter genes, 89 and 75 of them were specific to the SUS or LOE populations, respectively. A few of the SNPs identified may affect gene expression, protein function, substrate specificity or resistance development and may be useful for transporter inhibitor/anthelmintic drug design, or in order to anticipate resistance development. Keywords: Dirofilaria immitis

Association of angiotensin receptor 2 gene polymorphisms with pregnancy induced hypertension risk.

Science.gov (United States)

Li, Chenyang; Peng, Weijun; Zhang, Heng; Yan, Weirong

2018-05-01

To investigate the association of polymorphisms and haplotypes of angiotensin receptor 2 (AT2R) gene with pregnancy induced hypertension (PIH) in Chinese Han women. A case-control study was designed with 446 cases (gestational hypertension, GH: 124; pre-eclampsia, PE + eclampsia, E: 322) and 650 controls. rs5193, rs1403543 and rs12710567 of AT2R gene were genotyped. A logistic regression approach was applied to estimate the relationship between the polymorphisms and haplotypes of AT2Rgene with PIH risk. No relationship between AT2R gene polymorphisms and PIH was detected. The haplotype analysis also showed a negative result. rs5193, rs1403543 and rs12710567 of AT2R gene might have no effect on PIH risk among Chinese Han women.

Angiotensinogen gene polymorphisms in IDDM patients with diabetic nephropathy

DEFF Research Database (Denmark)

Tarnow, L; Cambien, Francois; Rossing, P

1996-01-01

Genotypic abnormalities of the renin-ANG system have been suggested as a risk factor for the development of diabetic nephropathy. Cleavage of angiotensinogen is the rate-limiting step in the activation of the renin-ANG system. The TT genotype of a polymorphism encoding threonine instead of methio......Genotypic abnormalities of the renin-ANG system have been suggested as a risk factor for the development of diabetic nephropathy. Cleavage of angiotensinogen is the rate-limiting step in the activation of the renin-ANG system. The TT genotype of a polymorphism encoding threonine instead...... of methionine (M235T) has been associated not only with increased plasma angiotensinogen concentration but also with essential hypertension. In addition, a polymorphism in the angiotensinogen gene substituting methionine for threonine (T174M) has been associated with hypertension in nondiabetic populations. We...... studied the relationship between these polymorphisms in the angiotensinogen gene in IDDM patients with diabetic nephropathy (121 men, 74 women, age 40.9 +/- 10 years, diabetes duration 27 +/- 8 years). There was no difference in M235T genotype distribution between IDDM patients with diabetic nephropathy...

Genetic polymorphism in three glutathione s-transferase genes and breast cancer risk

Energy Technology Data Exchange (ETDEWEB)

Woldegiorgis, S.; Ahmed, R.C.; Zhen, Y.; Erdmann, C.A.; Russell, M.L.; Goth-Goldstein, R.

2002-04-01

The role of the glutathione S-transferase (GST) enzyme family is to detoxify environmental toxins and carcinogens and to protect organisms from their adverse effects, including cancer. The genes GSTM1, GSTP1, and GSTT1 code for three GSTs involved in the detoxification of carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and benzene. In humans, GSTM1 is deleted in about 50% of the population, GSTT1 is absent in about 20%, whereas the GSTP1 gene has a single base polymorphism resulting in an enzyme with reduced activity. Epidemiological studies indicate that GST polymorphisms increase the level of carcinogen-induced DNA damage and several studies have found a correlation of polymorphisms in one of the GST genes and an increased risk for certain cancers. We examined the role of polymorphisms in genes coding for these three GST enzymes in breast cancer. A breast tissue collection consisting of specimens of breast cancer patients and non-cancer controls was analyzed by polymerase chain reaction (PCR) for the presence or absence of the GSTM1 and GSTT1 genes and for GSTP1 single base polymorphism by PCR/RFLP. We found that GSTM1 and GSTT1 deletions occurred more frequently in cases than in controls, and GSTP1 polymorphism was more frequent in controls. The effective detoxifier (putative low-risk) genotype (defined as presence of both GSTM1 and GSTT1 genes and GSTP1 wild type) was less frequent in cases than controls (16% vs. 23%, respectively). The poor detoxifier (putative high-risk) genotype was more frequent in cases than controls. However, the sample size of this study was too small to provide conclusive results.

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

International Nuclear Information System (INIS)

Hsieh, Yi-Chen; Lien, Li-Ming; Chung, Wen-Ting; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

2011-01-01

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 μg/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 μg/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 μg/l). - Highlights: →Arsenic metabolic genes might be associated with carotid atherosclerosis. → A case

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

Energy Technology Data Exchange (ETDEWEB)

Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

2011-08-15

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

Single nucleotide polymorphism in transcriptional regulatory regions and expression of environmentally responsive genes

International Nuclear Information System (INIS)

Wang, Xuting; Tomso, Daniel J.; Liu Xuemei; Bell, Douglas A.

2005-01-01

Single nucleotide polymorphisms (SNPs) in the human genome are DNA sequence variations that can alter an individual's response to environmental exposure. SNPs in gene coding regions can lead to changes in the biological properties of the encoded protein. In contrast, SNPs in non-coding gene regulatory regions may affect gene expression levels in an allele-specific manner, and these functional polymorphisms represent an important but relatively unexplored class of genetic variation. The main challenge in analyzing these SNPs is a lack of robust computational and experimental methods. Here, we first outline mechanisms by which genetic variation can impact gene regulation, and review recent findings in this area; then, we describe a methodology for bioinformatic discovery and functional analysis of regulatory SNPs in cis-regulatory regions using the assembled human genome sequence and databases on sequence polymorphism and gene expression. Our method integrates SNP and gene databases and uses a set of computer programs that allow us to: (1) select SNPs, from among the >9 million human SNPs in the NCBI dbSNP database, that are similar to cis-regulatory element (RE) consensus sequences; (2) map the selected dbSNP entries to the human genome assembly in order to identify polymorphic REs near gene start sites; (3) prioritize the candidate polymorphic RE containing genes by searching the existing genotype and gene expression data sets. The applicability of this system has been demonstrated through studies on p53 responsive elements and is being extended to additional pathways and environmentally responsive genes

Polymorphisms in the prion protein gene and in the doppel gene increase susceptibility for Creutzfeldt-Jakob disease

NARCIS (Netherlands)

E.A. Croes (Esther); B.Z. Alizadeh (Behrooz); A.M. Bertoli Avella (Aida); T.A.M. Rademaker (Tessa); J. Vergeer-Drop (Jeannette); B. Dermaut (Bart); J.J. Houwing-Duistermaat (Jeanine); D.P.W.M. Wientjens (Dorothee); A. Hofman (Albert); C. van Broeckhoven (Christine); C.M. van Duijn (Cornelia)

2004-01-01

textabstractThe prion protein gene (PRNP) plays a central role in the origin of Creutzfeldt-Jakob disease (CJD), but there is growing interest in other polymorphisms that may be involved in CJD. Polymorphisms upstream of PRNP that may modulate the prion protein production as well as polymorphisms in

Association of −330 interleukin-2 gene polymorphism with oral cancer

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Prithvi Kumar Singh

2017-01-01

>Results: IL-2 (−330A>C gene polymorphism was significantly associated with oral cancer whereas it was neither associated with clinicopathological status nor with cancer pain. The AC heterozygous genotype was significantly associated with oral cancer patients as compared to controls [odds ratio (OR: 3.0; confidence interval (CI: 2.14-4.20; PC gene polymorphism was also associated with oral cancer in tobacco smokers and chewers. >Interpretation & conclusions: Our results showed that oral cancer patients had significantly higher frequency of AA genotype but significantly lower frequency of AC genotype and C allele compared to controls. The IL-2 AC genotype and C allele of IL-2 (−330A>C gene polymorphisms could be potential protective factors and might reduce the risk of oral cancer in Indian population.

A Single Nucleotide Polymorphism in the Bax Gene Promoter Affects Transcription and Influences Retinal Ganglion Cell Death

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Sheila J Semaan

2010-03-01

Full Text Available Pro-apoptotic Bax is essential for RGC (retinal ganglion cell death. Gene dosage experiments in mice, yielding a single wild-type Bax allele, indicated that genetic background was able to influence the cell death phenotype. DBA/2J Bax+/− mice exhibited complete resistance to nerve damage after 2 weeks (similar to Bax −/− mice, but 129B6 Bax+/− mice exhibited significant cell loss (similar to wild-type mice. The different cell death phenotype was associated with the level of Bax expression, where 129B6 neurons had twice the level of endogenous Bax mRNA and protein as DBA/2J neurons. Sequence analysis of the Bax promoters between these strains revealed a single nucleotide polymorphism (T129B6 to CDBA/2J at position −515. A 1.5- to 2.5-fold increase in transcriptional activity was observed from the 129B6 promoter in transient transfection assays in a variety of cell types, including RGC5 cells derived from rat RGCs. Since this polymorphism occurred in a p53 half-site, we investigated the requirement of p53 for the differential transcriptional activity. Differential transcriptional activity from either 129B6 or DBA/2J Bax promoters were unaffected in p53−/− cells, and addition of exogenous p53 had no further effect on this difference, thus a role for p53 was excluded. Competitive electrophoretic mobility-shift assays identified two DNA-protein complexes that interacted with the polymorphic region. Those forming Complex 1 bound with higher affinity to the 129B6 polymorphic site, suggesting that these proteins probably comprised a transcriptional activator complex. These studies implicated quantitative expression of the Bax gene as playing a possible role in neuronal susceptibility to damaging stimuli.

Influence of FCGRT gene polymorphisms on pharmacokinetics of therapeutic antibodies.

Science.gov (United States)

Passot, Christophe; Azzopardi, Nicolas; Renault, Sylvaine; Baroukh, Nadine; Arnoult, Christophe; Ohresser, Marc; Boisdron-Celle, Michèle; Gamelin, Erick; Watier, Hervé; Paintaud, Gilles; Gouilleux-Gruart, Valérie

2013-01-01

The neonatal Fc receptor (FcRn) encoded by FCGRT is known to be involved in the pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs). Variability in the expression of FCGRT gene and consequently in the FcRn protein level could explain differences in PK observed between patients treated with mAbs. We studied whether the previously described variable number tandem repeat (VNTR) or copy number variation (CNV) of FCGRT are associated with individual variations of PK parameters of cetuximab. VNTR and CNV were assessed on genomic DNA of 198 healthy individuals and of 94 patients treated with the therapeutic mAb. VNTR and CNV were analyzed by allele-specific PCR and duplex real-time PCR with Taqman (®) technology, respectively. The relationship between FCGRT polymorphisms (VNTR and CNV) and PK parameters of patients treated with cetuximab was studied. VNTR3 homozygote patients had a lower cetuximab distribution clearance than VNTR2/VNTR3 and VNTR3/VNTR4 patients (p = 0.021). We observed no affects of VNTR genotype on elimination clearance. One healthy person (0.5%) and 1 patient (1.1%) had 3 copies of FCGRT. The PK parameters of this patient did not differ from those of patients with 2 copies. The FCGRT promoter VNTR may influence mAbs' distribution in the body. CNV of FCGRT cannot be used as a relevant pharmacogenetic marker because of its low frequency.

Analysis of IL-6, IL-10 and NF-κB Gene Polymorphisms in Aggressive and Chronic Periodontitis.

Science.gov (United States)

Toker, Hülya; Görgün, Emine Pirim; Korkmaz, Ertan Mahir

2017-06-01

Pro-inflammatory cytokines, interleukin-6 (IL-6), demonstrated to be suppressed by interleukin-10 (IL-10) are known to be regulated by the transcription factor nuclear factor-κB(NF-κB). The aim of this study was to ascertain the association between genetic polymorphism of these genes (IL-6(-174), IL-10(-597) and NF-κB1-94ins/del)) and chronic/aggressive periodontitis. Forty-five patients with chronic periodontitis (CP), 58 patients with aggressive periodontitis (AP) and 38 periodontally healthy subjects were included in this study. Genomic DNA was isolated from whole blood samples. The NF-κB, IL-6, and IL-10 polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Among subjects for the ins/ins genotypes of NF-κB1 gene, the AA genotypes of IL-10 presented a higher frequency in chronic periodontitis group than in healthy controls (p=0.023). A statistically significant difference in genotyping frequencies between AP group and healthy controls was observed for the IL-6 gene. The AA genotype of IL-10 was overrepresented in CP and AP groups compared to healthy controls (OR=9.93, 95% CI: 2.11-46.7, OR=5.7, 95% CI: 1.22-26.89, respectively). Within the limits of this study, it can be concluded that the IL-10 (-597) AA genotype is associated with susceptibility to chronic/aggressive periodontitis and IL-6 (-174) GG genotypes and G allele seems to be associated with aggressive periodontitis. Clinical relevance: The results of the current study indicate that IL-6 and IL-10 genotypes seem to be associated with aggressive periodontitis. Also, the AA genotypes of IL-10 presented a higher frequency in chronic periodontitis subjects with carrying NF-κB1 ins/ins genotypes. Copyright© by the National Institute of Public Health, Prague 2017

HEU/LEU-conversion of BER II successfully finished

International Nuclear Information System (INIS)

Haas, K.; Fischer, C.-O.; Krohn, H.

2000-01-01

The BER II (Berliner Experimental Reactor) research reactor is a swimming pool type reactor located in Berlin, Germany. The reactor operates with a thermal power of 10 MW and is primarily used to produce neutrons for neutron scattering experiments. The conversion from HEU- to LEU-fuel elements began in August, 1997. At the last RERTR Meeting 1999 in Budapest, Hungary, Hahn-Meitner-Institut (HMI) presented a 'Status Report' on the conversion of 10 HEU/LEU mixed cores. In February 2000, HMI finished the HEU/LEU-conversion. Hereby, the first pure LEU-standard-core went into operation. Our second LEU-core just ends its operation at the end of July. The third LEU-core will be built up in the beginning of August. The average burn-up rate was improved from 50 - 55% (HEU) to 60 - 65% (LEU). Therefore, only 14 elements/year are now used instead of 28/year. The following report describes our first steps in building pure LEU-cores from mixed HEU/LEU-cores, as well as our initial experience using the pure LEU-cores. (author)

Polymorphisms in human DNA repair genes and head and neck ...

Indian Academy of Sciences (India)

Abstract. Genetic polymorphisms in some DNA repair proteins are associated with a number of malignant transformations like head and ... Such studies may benefit from analysis of multiple genes or polymorphisms and from the ... low survival and high morbidity when diagnosed in advanced ...... racial and/or ethnic cohort.

Lower expressed miR-198 and its potential targets in hepatocellular carcinoma: a clinicopathological and in silico study

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Huang WT

2016-08-01

Full Text Available Wen-Ting Huang,1,* Han-Lin Wang,1,* Hong Yang,2 Fang-Hui Ren,1 Yi-Huan Luo,1 Chun-Qin Huang,1 Yue-Ya Liang,1 Hai-Wei Liang,1 Gang Chen,1 Yi-Wu Dang1 1Department of Pathology, 2Department of Ultrasonography, First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China *These authors contributed equally to this work Purpose: To investigate the clinicopathological value and potential roles of microRNA-198 (miR-198 in hepatocellular carcinoma (HCC.Methods: Ninety-five formalin-fixed paraffin-embedded HCC and the para-cancerous liver tissues were gathered. Real-time reverse transcription quantitative polymerase chain reaction was applied to determine the miR-198 expression. The association between the miR-198 expression and clinicopathological features was examined. Meanwhile, potential target messenger RNAs of miR-198 in HCC were obtained from 14 miRNA prediction databases and natural language processing method, in which we pooled the genes related to the tumorigenesis and progression of HCC and classified them by their frequency. The selected target genes were finally analyzed in the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway.Results: miR-198 expression was significantly lower in HCC than that in adjacent noncancerous liver tissues (1.30±0.72 vs 2.01±0.58, P<0.001. Low miR-198 expression was also correlated to hepatitis C virus infection (r=-0.48, P<0.001, tumor capsular infiltration (r=-0.43, P<0.001, metastasis (r=-0.26, P<0.010, number of tumor nodes (r=-0.25, P=0.013, vaso-invasion (r=-0.24, P=0.017, and clinical tumor node metastasis stage (r=-0.23, P=0.024. Altogether, 1,048 genes were achieved by the concurrent prediction from at least four databases and natural language processing indicated 1,800 genes for HCC. Further, 127 overlapping targets were further proceeded with for pathway analysis. The most enriched Gene Ontology terms in the potential target messenger RNAs of mi

Prevalence of coagulase gene polymorphism in Staphylococcus aureus isolates causing bovine mastitis

DEFF Research Database (Denmark)

Aarestrup, Frank Møller; Dangler, C. A.; Sordillo, L. M.

1995-01-01

This study was conducted to investigate polymorphism of the coagulase gene of Staphylococcus aureus causing bovine mastitis. One hundred eighty-seven strains of S. aureus were isolated from bovine mastitic milk samples obtained from 187 different Danish dairy farms. The isolates were characterised......% of the isolates. The ease of analysing coagulase gene polymorphisms among a large number of strains, and the multiple distinct polymorphic patterns generated, supports the use of this technique in epidemiological investigations of bovine mastitis. The predominating variants may have predelection for causing...

Pro-inflammatory cytokine single nucleotide polymorphisms in Kawasaki disease.

Science.gov (United States)

Assari, Raheleh; Aghighi, Yahya; Ziaee, Vahid; Sadr, Maryam; Rahmani, Farzaneh; Rezaei, Arezou; Sadr, Zeinab; Moradinejad, Mohammad Hassan; Raeeskarami, Seyed Reza; Rezaei, Nima

2016-07-25

Kawasaki disease (KD) is a systemic vasculitis of children associated with cardiovascular sequelae. Proinflammatory cytokines play a major role in KD pathogenesis. However, their role is both influenced and modified by regulatory T-cells. IL-1 gene cluster, IL-6 and TNF-α polymorphisms have shown significant associations with some vasculitides. Herein we investigated their role in KD. Fifty-five patients with KD who were randomly selected from referrals to the main pediatric hospital were enrolled in this case-control study. Single nucleotide polymorphisms (SNPs) of the following genes were assessed in patients and 140 healthy subjects as control group: IL-1α at -889 (rs1800587), IL-1β at -511 (rs16944), IL-1β at +3962 (rs1143634), IL-1R at Pst-I 1970 (rs2234650), IL-1RN/A at Mspa-I 11100 (rs315952), TNF-α at -308 (rs1800629), TNF-α at -238, IL-6 at -174 (rs1800795) and IL-6 at +565. Twenty-one percent of the control group had A allele at TNF-α -238 while only 8% of KD patients had A allele at this position (P = 0.003, OR [95%CI] = 0.32 [0.14-0.71]). Consistently, TNF-α genotype GG at -238 had significant association with KD (OR [95% CI] = 4.31 [1.79-10.73]). Most controls carried the CG genotype at IL-6 -174 (n = 93 [66.9%]) while GG genotype was the most common genotype (n = 27 [49%]) among patients. Carriers of the GG haplotype at TNF-α (-308, -238) were significantly more prevalent among the KD group. No association was found between IL-1 gene cluster, allelic or haplotypic variants and KD. TNF-α GG genotype at -238 and GG haplotype at positions -308 and -238 were associated with KD in an Iranian population. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.

Science.gov (United States)

van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O

1992-01-01

Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes. Images PMID:1360671

The role of TNF-α and TNF-β gene polymorphism in the pathogenesis of Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Hannan Al- Rayes

2013-01-01

Full Text Available Rheumatoid arthritis (RA is a chronic systemic inflammatory disorder of unknown etiology that affects the synovial membrane of multiple joints. The clinical presentation of RA may vary from mild to severe with excessive erosions of periarticular bone leading to the loss of functional capacity. Both genetic and environmental factors are important in the development of this disorder. The genetic contribution to susceptibility for RA is underlined by a three-to four-fold higher concordance percentage for clinically expressed disease in monozygotic twins compared to dizygotic twins. The severity and long term outcome of RA have also been related to various genetic factors. Tumor necrosis factor (TNF, a pro-inflammatory cytokine, is involved in the pathogenesis of a variety of autoimmune disorders, including RA. A large number of studies have been undertaken to determine the role of TNF-α promoter polymorphisms in the pathogenesis of RA. On the other hand few attempts have been made to identify the association between TNF-α (lymphotoxin-alfa polymorphism and RA. In this narrative review of published literature, an attempt has been made to determine the association between TNF-α promoter polymorphisms at positions –308, –238, –489, –857, –863 and TNF-β at +252 with respect to susceptibility to and severity of RA, as well as response to drug therapy. In spite of intra-and inter-ethnic variations, analysis of data suggests a significant role of TNF-α/TNF-β polymorphisms in determining the susceptibility/severity of RA and responsiveness to anti-TNF drug therapy. The TNF gene polymorphisms may be an interesting target for novel strategies to prevent RA and/or in its early treatment. Further studies using larger samples are needed to pinpoint the regulatory polymorphisms or haplotypes and their effects on the development of certain manifestations in RA.

The first report of prion-related protein gene (PRNT) polymorphisms in goat.

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Kim, Yong-Chan; Jeong, Byung-Hoon

2017-06-01

Prion protein is encoded by the prion protein gene (PRNP). Polymorphisms of several members of the prion gene family have shown association with prion diseases in several species. Recent studies on a novel member of the prion gene family in rams have shown that prion-related protein gene (PRNT) has a linkage with codon 26 of prion-like protein (PRND). In a previous study, codon 26 polymorphism of PRND has shown connection with PRNP haplotype which is strongly associated with scrapie vulnerability. In addition, the genotype of a single nucleotide polymorphism (SNP) at codon 26 of PRND is related to fertilisation capacity. These findings necessitate studies on the SNP of PRNT gene which is connected with PRND. In goat, several polymorphism studies have been performed for PRNP, PRND, and shadow of prion protein gene (SPRN). However, polymorphism on PRNT has not been reported. Hence, the objective of this study was to determine the genotype and allelic distribution of SNPs of PRNT in 238 Korean native goats and compare PRNT DNA sequences between Korean native goats and several ruminant species. A total of five SNPs, including PRNT c.-114G > T, PRNT c.-58A > G in the upstream of PRNT gene, PRNT c.71C > T (p.Ala24Val) and PRNT c.102G > A in the open reading frame (ORF) and c.321C > T in the downstream of PRNT gene, were found in this study. All five SNPs of caprine PRNT gene in Korean native goat are in complete linkage disequilibrium (LD) with a D' value of 1.0. Interestingly, comparative sequence analysis of the PRNT gene revealed five mismatches between DNA sequences of Korean native goats and those of goats deposited in the GenBank. Korean native black goats also showed 5 mismatches in PRNT ORF with cattle. To the best of our knowledge, this is the first genetic research of the PRNT gene in goat.

Polymorphism of the ACE gene and the risk of obstructive sleep apnoea.

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Chmielewska, Izabela; Mlak, Radosław; Krawczyk, Paweł; Czukiewska, Ewa; Milanowski, Janusz

2013-01-01

Obstructive sleep apnoea/hypopnea syndrome (OSA) is characterized by obstruction of the upper airway during sleep, resulting in repetitive breathing pauses accompanied by oxygen desaturation and arousal from sleep. Among the candidate genes affecting the risk of OSA, genes whose polymorphisms influence the development of diseases with similar pathogenesis such as OSA could be listed: APOE, genes for leptin and leptin receptor, TNFA1, ADRB2 and ACE (gene for angiotensin-converting enzyme). Until now there has been a confirmed relationship between ACE gene polymorphism and cardiovascular diseases, but its effect on the incidence of OSA is debatable. The aim of this study was to investigate the effect of ACE gene insertion/deletion (I/D) polymorphism on the risk of OSA. Fifty-five patients with confirmed diagnose of OSA and qualified to CPAP therapy entered the study. The control group included 50 subjects who did not complain of any sleep related symptoms. Diagnose of OSA was set on the basis of full overnight polysomnography together with Epworth Sleepiness Scale according to American Academy of Sleep Medicine guidelines. DNA was isolated from peripheral blood leukocytes with Qiagen DNA mini Kit. ACE gene polymorphism was determined in genomic DNA using allele specific polymerase chain reaction. Different sizes of PCR products were observed on agarose gel electrophoresis. There were non-significant differences in the frequency of ACE genotypes. However, allele D had significantly lower prevalence in the study group than in the control group. (χ(2) = 4.25 p = 0.04). Moreover, I allele carriers had a threefold greater risk of developing OSA (HR = 2.748, 95% CI = 1.029-7.340, p gene polymorphism might be useful to determine the risk of developing OSA in clinically predisposed patients.

Glutathione S-transferase gene polymorphisms in presbycusis.

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Ateş, Nurcan Aras; Unal, Murat; Tamer, Lülüfer; Derici, Ebru; Karakaş, Sevim; Ercan, Bahadir; Pata, Yavuz Selim; Akbaş, Yücel; Vayisoğlu, Yusuf; Camdeviren, Handan

2005-05-01

Glutathione and glutathione-related antioxidant enzymes are involved in the metabolism and detoxification of cytotoxic and carcinogenic compounds as well as reactive oxygen species. Reactive oxygen species generation occurs in prolonged relative hypoperfusion conditions such as in aging. The etiology of presbycusis is much less certain; however, a complex genetic cause is most likely. The effect of aging shows a wide interindividual range; we aimed to investigate whether profiles of (glutathione S-transferase (GST) M1, T1 and P1 genotypes may be associated with the risk of age-related hearing loss. We examined 68 adults with presbycusis and 69 healthy controls. DNA was extracted from whole blood, and the GSTM1, GSTT1 and GSTP1 polymorphisms were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of presbycusis were examined by use of logistic regression analyses to calculate odds ratios and 95% confidence intervals. Gene polymorphisms at GSTM1, GSTT1, and GSTP1 in subjects with presbycusis were not significantly different than in the controls (p > 0.05). Also, the combinations of different GSTM1, GSTT1, and GSTP1 genotypes were not an increased risk of presbycusis (p > 0.05). We could not demonstrate any significant association between the GSTM1, GSTT1, and GSTP1 polymorphism and age-related hearing loss in this population. This may be because of our sample size, and further studies need to investigate the exact role of GST gene polymorphisms in the etiopathogenesis of the presbycusis.

Analysis of Human Bradykinin Receptor Gene and Endothelial Nitric Oxide Synthase Gene Polymorphisms in End-Stage Renal Disease Among Malaysians

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R. Vasudevan

2014-06-01

Full Text Available The aim of this study was to determine the association of the c.894G>T; p.Glu298Asp polymorphism and the variable number tandem repeat (VNTR polymorphism of the endothelial nitric oxide synthase (eNOS gene and c.181C>T polymorphism of the bradykinin type 2 receptor gene (B2R in Malaysian end-stage renal disease (ESRD subjects.

Significant association of interleukin-4 gene intron 3 VNTR polymorphism with susceptibility to knee osteoarthritis.

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Yigit, Serbulent; Inanir, Ahmet; Tekcan, Akın; Tural, Ercan; Ozturk, Gokhan Tuna; Kismali, Gorkem; Karakus, Nevin

2014-03-01

Interleukin-4 (IL-4) is a strong chondroprotective cytokine and polymorphisms within this gene may be a risk factor for osteoarthritis (OA). We aimed to investigate genotype and allele frequencies of IL-4 gene intron 3 variable number of tandem repeats (VNTR) polymorphism in patients with knee OA in a Turkish population. The study included 202 patients with knee OA and 180 healthy controls. Genomic DNA was isolated and IL-4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers followed by restriction fragment length polymorphism (RFLP) analysis. Our result show that there was statistically significant difference between knee OA patients and control group with respect to IL-4 genotype distribution and allele frequencies (p=0.000, OR: 0.20, 95% CI: 0.10-0.41, OR: 0.22, 95% CI: 0.12-0.42, respectively). Our findings suggest that there is an association of IL-4 gene intron 3 VNTR polymorphism with susceptibility of a person for development of knee OA. As a result, IL-4 gene intron 3 VNTR polymorphism could be a genetic marker in OA in a Turkish study population. This is the first association study that evaluates the associations between IL-4 gene VNTR polymorphism and knee OA. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Polymorphism of glucagon-like peptide-1 receptor gene (rs1042044 ...

African Journals Online (AJOL)

patience

2015-02-16

Feb 16, 2015 ... turnover via GLP-1 receptors (GLP1Rs) in postmenopausal state. Furthermore, polymorphisms in. GLP1R gene were suggested to affect the function of GLP1Rs and be associated with many diseases. However, the relationships between GLP1R polymorphisms and osteoporosis susceptibility and bone.

CYTOKINE GENE POLYMORPHISMS AS PREDICTORS OF CHRONIC PAIN SYNDROME IN ONCOLOGY

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O. P. Bobrova

2017-01-01

Full Text Available The literature review on the role of cytokine gene polymorphisms in the development of chronic pain in cancer patients was presented using MedLine, PubMed, NEB elibrary.ru, WileyOnlineLibrary, WebofScience, OxfordUniversityPress and SAGEPremier databases for years 1995 to 2016. The role of inter-individual differences based on cytokine gene polymorphisms and their receptors for personalized anesthetic and accompanying treatment in oncology was shown.

Tetranucleotide repeat polymorphism at the human prostatic acid phosphatase (ACPP) gene

Energy Technology Data Exchange (ETDEWEB)

Polymeropoulos, M H; Xiao, Hong; Rath, D S; Merril, C R [National Inst. of Mental Health Neuroscience Center, Washington, DC (United States)

1991-09-11

The polymorphic (AAAT){sub n} repeat begins at base pair 2342 of the human prostatic acid phosphatase gene on chromosome 3q21-qter. The polymorphism can be typed using the polymerase chain reaction (PCR) as described previously. The predicted length of the amplified sequence was 275 bp. Co-dominant segregation was observed in two informative families. The human prostatic acid phosphatase gene has been assigned to chromosome 3q21-qter.

Hepatitis B virus DNA polymerase gene polymorphism based ...

African Journals Online (AJOL)

Hepatitis B virus DNA polymerase gene polymorphism based prediction of genotypes in chronic HBV patients from Western India. Yashwant G. Chavan, Sharad R. Pawar, Minal Wani, Amol D. Raut, Rabindra N. Misra ...

Cytokine gene polymorphisms and their association with cervical ...

African Journals Online (AJOL)

Maneesh Kumar Gupta

2015-11-17

Nov 17, 2015 ... gene polymorphisms with cervical cancer in a north Indian population. Genotyping of ... diseases like coronary heart disease, breast cancer, cervical cancer etc ...... Environmental risk factors for prevention and molecular inter-.

Polymorphisms of genes involved in polycyclic aromatic hydrocarbons’ biotransformation and atherosclerosis

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Marinković, Natalija; Pašalić, Daria; Potočki, Slavica

2013-01-01

Polycyclic aromatic hydrocarbons (PAHs) are among the most prevalent environmental pollutants and result from the incomplete combustion of hydrocarbons (coal and gasoline, fossil fuel combustion, byproducts of industrial processing, natural emission, cigarette smoking, etc.). The first phase of xenobiotic biotransformation in the PAH metabolism includes activities of cytochrome P450 from the CYP1 family and microsomal epoxide hydrolase. The products of this biotransformation are reactive oxygen species that are transformed in the second phase through the formation of conjugates with glutathione, glucuronate or sulphates. PAH exposure may lead to PAH-DNA adduct formation or induce an inflammatory atherosclerotic plaque phenotype. Several genetic polymorphisms of genes encoded for enzymes involved in PAH biotransformation have been proven to lead to the development of diseases. Enzyme CYP P450 1A1, which is encoded by the CYP1A1 gene, is vital in the monooxygenation of lipofilic substrates, while GSTM1 and GSTT1 are the most abundant isophorms that conjugate and neutralize oxygen products. Some single nucleotide polymorphisms of the CYP1A1 gene as well as the deletion polymorphisms of GSTT1 and GSTM1 may alter the final specific cellular inflammatory respond. Occupational exposure or conditions from the living environment can contribute to the production of PAH metabolites with adverse effects on human health. The aim of this study was to obtain data on biotransformation and atherosclerosis, as well as data on the gene polymorphisms involved in biotransformation, in order to better study gene expression and further elucidate the interaction between genes and the environment. PMID:24266295

Endothelial nitric oxide synthase gene polymorphisms associated ...

African Journals Online (AJOL)

Endothelial nitric oxide synthase (NOS3) is involved in key steps of immune response. Genetic factors predispose individuals to periodontal disease. This study's aim was to explore the association between NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained ...

[Prevalence of gene polymorphisms associated with immune-dependent diseases in the populations of North Eurasia].

Science.gov (United States)

Cherednichenko, A A; Trifonova, E A; Vagaitseva, K V; Bocharova, A V; Varzari, A M; Radzhabov, M O; Stepanov, V A

2015-01-01

The data on distribution of genetic diversity in gene polymorphisms associated with autoimmune and allergic diseases and with regulation of immunoglobulin E and cytokines levels in 26 populations of the Northern Eurasia is presented. Substantial correlation between the values of average expected heterozygosity by 44 gene polymorphisms with climatic and geographical factors has not been revealed. Clustering of population groups in correspondence with their geographic locations is observed. The degree of gene differentiation among populations and the selective neutrality of gene polymorphisms have been assessed. The results of our work evidence the substantial genetic diversity and differentiation of human populations by studied genes.

Tetra primer ARMS-PCR relates folate/homocysteine pathway genes and ACE gene polymorphism with coronary artery disease.

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Masud, Rizwan; Qureshi, Irfan Zia

2011-09-01

Cardiovascular disorders and coronary artery disease (CAD) are significant contributors to morbidity and mortality in heart patients. As genes of the folate/homocysteine pathway have been linked with the vascular disease, we investigated association of these gene polymorphisms with CAD/myocardial infarction (MI) using the novel approach of tetraprimer ARMS-PCR. A total of 230 participants (129 MI cases, 101 normal subjects) were recruited. We genotyped rs1801133 and rs1801131 SNPs in 5'10' methylenetetrahydrofolate reductase (MTHFR), rs1805087 SNP in 5' methyltetrahydrofolate homocysteine methyltransferase (MTR), rs662 SNP in paroxanse1 (PON1), and rs5742905 polymorphism in cystathionine beta synthase (CBS). Angiotensin converting enzyme (ACE) insertion/deletion polymorphism was detected through conventional PCR. Covariates included blood pressure, fasting blood sugar, serum cholesterol, and creatinine concentrations. Our results showed allele frequencies at rs1801133, rs1801131, rs1805087 and the ACE insertion/deletion (I/D) polymorphism varied between cases and controls. Logistic regression, after adjusting for covariates, demonstrated significant associations of rs1801133 and rs1805087 with CAD in the additive, dominant, and genotype model. In contrast, ACE I/D polymorphism was significantly related with CAD where recessive model was applied. Gene-gene interaction against the disease status revealed two polymorphism groups: rs1801133, rs662, and rs1805087; and rs1801131, rs662, and ACE I/D. Only the latter interaction maintained significance after adjusted for covariates. Our study concludes that folate pathway variants exert contributory influence on susceptibility to CAD. We further suggest that tetraprimer ARMS-PCR successfully resolves the genotypes in selected samples and might prove to be a superior technique compared to the conventional approach.

[Polymorphism of vitamin D receptor gene Fok I in Mongolian population of China].

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Xing, Shao-ji; Zhou, Li-she; Xu, Xiu-ju

2006-04-01

To investigate the polymorphism distribution of vitamin D receptor (VDR) gene Fok I in Mongolian population of China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to analyze three genotypes FF, Ff and ff in the start codon of VDR gene (Fok I) in unrelated normal healthy Mongolian individuals of China. In the population, we obtained the allelic frequencies of 57% and 43% for (F) and (f) allele and the percentage of genotypes FF, Ff and ff to be 31%, 52%, and 17% respectively. The polymorphism frequency and distribution of this VDR gene Fok I in Mongolian population of China exhibit its own characteristics.

Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

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Nooshin Ghodsian

2016-01-01

Full Text Available Background. Atrial natriuretic peptide (ANP considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P<0.05. Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population.

Association of Interleukin-10 gene promoter polymorphisms with obstructive sleep apnea.

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Özdaş, Sibel; Özdaş, Talih; Acar, Mustafa; Erbek, Selim S; Köseoğlu, Sabri; Göktürk, Gökhan; Izbirak, Afife

2016-05-01

Interleukin-10 (IL) is an anti-inflammatory cytokine that regulates normal sleep patterns, and recent studies have reported that it is a potential useful biomarker to identify presence and severity of sleep apnea syndrome (OSAS). Promoter polymorphisms of IL-10 gene have been associated with altered expression levels, which contributes to OSAS. The aim of this study was to determine the prevalence of -1082 G/A, -819 C/T, and -592 C/A promoter polymorphisms of IL-10 gene in individuals with OSAS and controls. An open-label study was performed in the Otorhinolaryngology and Sleep Disorders Outpatient Clinics. One hundred four cases with OSAS were included as the study group, and 78 individuals without OSAS were included as the controls. DNAs were extracted from peripheral blood leukocytes, and the sites that encompassed those polymorphisms were identified by DNA sequencing analyses. Data were analyzed with SNPStats and multifactor dimensionality reduction (MDR) software. The prevalence of OSAS was higher in males in the study group when compared to controls (P = 0.0003). The IL-10-1082 G/A, -819 C/T, and -592 C/A SNPs, and their minor alleles were associated with a significantly increased risk for OSAS compared to the controls (P ˂ 0.05 for all). Furthermore, ATA haplotype frequency was significantly higher in the study group compared to the control group, but the GCC haplotype frequency was lower (P = 0.0001 and P = 0.0001). As indicated in MDR analysis, combinations of IL-10 gene were associated with OSAS in single-, double-, and triple-locus analyses. The prevalences of the IL-10 gene promoter polymorphisms were different in OSAS patients and the controls in Turkish population. IL-10 gene polymorphisms may lead to altered inflammatory cascade, which might contribute to OSAS. Further studies on larger cohorts are needed to validate our findings.

AT1 Receptor Gene Polymorphisms in relation to Postprandial Lipemia

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B. Klop

2012-01-01

Full Text Available Background. Recent data suggest that the renin-angiotensin system may be involved in triglyceride (TG metabolism. We explored the effect of the common A1166C and C573T polymorphisms of the angiotensin II type 1 receptor (AT1R gene on postprandial lipemia. Methods. Eighty-two subjects measured daytime capillary TG, and postprandial lipemia was estimated as incremental area under the TG curve. The C573T and A1166C polymorphisms of the AT1R gene were determined. Results. Postprandial lipemia was significantly higher in homozygous carriers of the 1166-C allele (9.39±8.36 mM*h/L compared to homozygous carriers of the 1166-A allele (2.02±6.20 mM*h/L (P<0.05. Postprandial lipemia was similar for the different C573T polymorphisms. Conclusion. The 1166-C allele of the AT1R gene seems to be associated with increased postprandial lipemia. These data confirm the earlier described relationships between the renin-angiotensin axis and triglyceride metabolism.

Personalized Medicine Digoxin Theraphy in Individuals with MDR Gene Polymorphism

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Em Sutrisna

2015-06-01

Full Text Available Digoxin is one of digitalis drugs. Wider applicability to heart failure and arrhythmias (supraventricular requires fairly strict scrutiny because of its narrow therapeutic index. Digoxin is a substrate of P-glycoprotein (P-gp encoded by multi drugs resistance-1 (MDR1. MDR-1 gen located on chromosome 7q21.1. This gene contains 28 exons that encoded a protein of 1280 amino acids. This gene plays an important role in the absorption, distribution and elimination of many drugs. MDR1C3435T polymorphism occurs in exon 26. There are three types of MDR1C3435T gene namely MDR1C3435T CC, MDR1C3435T CT and MDR1C3435T TT. These polymorphisms will affect to the formation of P-gp and consequently to change the kinetic profile of digoxin. The change of kinetic profile causes changes in the digoxin blood levels. The method used in this review is data search based on pubmed, medline, and embase with keywords MDR and digoxin. There are several different studies of the influence of polymorphisms MDR1C3435T on blood digoxin levels. Increased levels of digoxin in the blood due to polymorphism of MDR1C3435T will be at risk of digitalis intoxication. Long-term digoxin treatment or large dose should consider the patient’s genetic profile. Distribution of polymorphism of MDR1C3435T in Javanese population is approximately TT (0,10, CT (0,52, and CC(0, 38.

Association of Vitamin D receptor gene polymorphisms with metabolic syndrome and its components among adult Arabs from the United Arab Emirates.

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Hasan, Hayder A; AbuOdeh, Ra'ed O; Muda, Wan Abdul Manan Bin Wan; Mohamed, Hamid Jan Bin Jan; Samsudin, Ab Rani

2017-12-01

The aim was to investigate relationships of Vitamin D receptor gene (VDR) polymorphisms to the components of MetS among Arabs adult residing in the United Arab Emirates. A cross-sectional study of 198 Arabs adult (50 males and 148 females). Serum levels of glucose, vitamin D, HDL-C, and TG, and blood pressure were measured. FokI, BsmI & TaqI genotyping of VDR were investigated using PCR-RFLP technique. Age of the participants was 21(9) years with a BMI of 26.8(7.8) kg/m 2 . About 15% had MetS with serum vitamin D levels of 25.5(18.2) nmol/L. VDR genotyping yielded: FokI: 57.1% FF and 38.9% Ff, BsmI: 29.8% bb and 51.5% Bb, while TaqI showed 39.4% TT and 43.4% Tt. The ff carriers had higher total cholesterol [174(12.4) mg/dl] than FF and Ff genotypes. Bb carriers showed higher BMI and LDL-C than BB and bb genotypes. In females, FokI VDR polymorphism showed significant association with systolic blood pressure (SBP) and F allele carriers were at higher risk of developing high SBP [x 2 =4.4, df1, OR=0.29 (95%CI: 0.087-0.98), p=0.035]. VDR gene polymorphisms were not associated with MetS, yet it may affect the severity of some of components of MetS, namely the association of BsmI with obesity, FokI and BsmI with dyslipidemia and FokI with SBP. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Research on the relativity between gene polymorphism and children cardiac insufficiency.

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He, X-H; Li, C-L; Ling, N; Wang, Q-W; Wang, Z-Z; An, X-J

2017-08-01

We analyzed the relationship between Mink-S27 gene polymorphism and children with cardiac insufficiency. From April 2013 to April 2015, we enrolled 73 cases of children with cardiac insufficiency for this study, and all 73 were placed in the observation group. 76 normal cases were selected for the control group. Restriction fragment length polymorphism (RFLP) was used to make polymorphism analysis of the Mink-S27. Our results showed no significant differences in Mink-S27 genotype and allele distribution in both observation and control groups (p>0.05). In lesion samples collected from children with cardiac insufficiency, we detected significant difference in AA, CC genotype frequency and allele frequency between the observation group and the control group (prelatively high. GNAS2 gene polymorphism was associated with the prevalence of cardiac insufficiency in children. And also the patients' condition was correlated to the frequency of different genotypes and alleles.

Polymorphism of calpastatin gene in Arabic sheep using PCR- RFLP

African Journals Online (AJOL)

Calpastatin has been known as candidate gene in muscle growth efficiency and meat quality. This gene has been located to chromosome 5 of sheep. In order to evaluate the calpastatin gene polymorphism, random blood sample were collected from 111 Arabic ram sheep from different regions. The DNA extraction was ...

Correlation between endometriosis combined with infertility and STAT3 gene polymorphisms

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Juan Hu

2016-05-01

Full Text Available Objective: To investigate the correlation between STAT3 gene polymorphisms and endometriosis complicated with infertility. Methods: A total of 35 patients with endometriosis complicated with infertility and 35 cases of healthy volunteer from October 2014 to October 2015 in our hospital were selected as research objects. STAT3 gene polymorphisms of all objects were detected by PCR-RFLP method. Results: Polymorphic sites of STAT3 gene rs2293152 were expressed as three genotypes, namely, CC, GC, and GG. There were 18 cases, 10 cases and 7 cases of type CC, GC and GG in the observation group, accounted for 51.43%, 28.57% and 20.00%, respectively. There were 29 cases, 3 cases and 3 cases of type CC, GC and GG in the control group, accounted for 82.86%, 8.57% and 8.57%. There was a statistically difference` between the two groups. The frequency of C and G allele in the observation group and the control group were 65.71%, 34.29% and 87.14%, 12.86%, respectively. There were statistically significant differences between two groups. In addition, compared with the CC genotype, genotype G might increase the risk of the disease. Conclusions: The susceptibility of endometriosis complicated with infertility may be associated with STAT3 gene polymorphism and women who carried the G allele may have an increased the risk of the disease.

Interleukin 17 receptor gene polymorphism in periimplantitis and chronic periodontitis.

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Mahdi Kadkhodazadeh

2013-06-01

Full Text Available Gene polymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R gene polymorphism (rs879576 with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject's arm vein and transferred to tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP technique. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant. There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239. Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239. The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.

Interleukin 17 Receptor Gene Polymorphism in Periimplantitis and Chronic Periodontitis

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Mahdi Kadkhodazadeh

2013-05-01

Full Text Available Gene polymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R gene polymorphism (rs879576 with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject’s arm vein and transferred to tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP technique. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant. There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239. Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239. The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.

Association between polymorphism at 3 ׳UTR of urokinase gene and risk of calcium

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S. Morovvati

2016-06-01

Full Text Available Background: Kidney stone is a common multifactorial disease in Iran. Environmental and genetic factors including single nucleotide polymorphism (SNP affect the incidence of kidney stones. Objective: The aim of this study was to determine the association of +4065 T/C polymorphism at 3′untranslated region (3'UTR of urokinase gene and calcium kidney stones. Methods: This case-control study was conducted on 70 patients with history of calcium kidney stones as case group and 70 healthy subjects as control group in the Baqiyatallah hospital in 2013. The polymorphism was assessed using the Allele Specific PCR (AS-PCR method. Allele and genotype frequencies of the two groups were compared using 2x2 contingency tables. Hardy-Weinberg equilibrium was compared between the two groups using Chi-square test. Findings: Of 70 cases, 10 (15% were heterozygous and 24 (34% were homozygous for the polymorphism. Of 70 controls, 25 (35% were heterozygous for the polymorphism. The frequency of mutant T allele was 41% in the case group and 18% in the control group. The frequency of mutant C allele was 59% in the case group and 82% in the control group. The risk of calcium kidney stones in carriers of the mutant allele was 1.7 times higher than non-carriers (OR: 1.7. Conclusion: With regards to the results, it seems that there is a significant association between the polymorphism at 3 ׳UTR of urokinase gene and formation of calcium kidney stones. Urokinase gene polymorphism may be introduced as a candidate gene involved in calcium stone formation.

The Association of PPARγ Pro12Ala and C161T Polymorphisms with Polycystic Ovary Syndrome and Their Influence on Lipid and Lipoprotein Profiles

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Zohreh Rahimi

2018-05-01

Full Text Available Background The aim of present study was to clarify the role of the peroxisome proliferator-activated receptor (PPAR γ Pro12Ala and C161T polymorphisms in the pathogenesis of polycystic ovary syndrome (PCOS and their influence on lipid and lipoprotein profiles of patients. Materials and Methods The present cross-sectional study consisted of 50 women with PCOS, who referred to the Kermanshah University of Medical Sciences Clinic between April and October 2015, and 233 unrelated age-matched healthy women from the same region (West Iran. The PPARγ Pro12Ala and PPARγ C161T polymorphisms were gen- otyped using the polymerase chain reaction-restriction fragment length polymorphism method. Fasting blood sugar (FBS, serum triglycerides (TG, cholesterol, low density lipoprotein- cholesterol (LDL-C, high density lipoprotein- cholesterol (HDL-C and estradiol levels were measured. Results The serum level of estradiol was significantly lower in PCOS patients compared to healthy women. The PPARγ Pro12Ala (CG genotype increased the risk of PCOS 2.96-fold. The frequency of the PPARγ T allele (at C161T was 21% in patients and 17.2% in controls with no significant difference (P=0.52. In all studied individuals, the PPARγ CG geno- type was associated with significantly higher levels of TG. However, significantly lower levels of total cholesterol and LDL-C were observed in PPARγ TT individuals compared with those with the CC genotype. Within the PCOS group, the PPARγ CG genotype was significantly associated with lower levels of estradiol compared with the CC genotype. Also, the CG genotype was significantly associated with higher levels of TG when compared with the CC genotype. Conclusion Our study shows that, unlike PPARγ C161T, PPARγ Pro12Ala is associated with the risk of PCOS. Also, we found that the lipid and lipoprotein profiles significantly vary based on PPARγ Pro12Ala and C161T genotypes.

Gene Expression and Polymorphism of Myostatin Gene and its Association with Growth Traits in Chicken.

Science.gov (United States)

Dushyanth, K; Bhattacharya, T K; Shukla, R; Chatterjee, R N; Sitaramamma, T; Paswan, C; Guru Vishnu, P

2016-10-01

Myostatin is a member of TGF-β super family and is directly involved in regulation of body growth through limiting muscular growth. A study was carried out in three chicken lines to identify the polymorphism in the coding region of the myostatin gene through SSCP and DNA sequencing. A total of 12 haplotypes were observed in myostatin coding region of chicken. Significant associations between haplogroups with body weight at day 1, 14, 28, and 42 days, and carcass traits at 42 days were observed across the lines. It is concluded that the coding region of myostatin gene was polymorphic, with varied levels of expression among lines and had significant effects on growth traits. The expression of MSTN gene varied during embryonic and post hatch development stage.

Vitamin D Receptor Gene Polymorphisms Associated with Childhood Autism.

Science.gov (United States)

Cieślińska, Anna; Kostyra, Elżbieta; Chwała, Barbara; Moszyńska-Dumara, Małgorzata; Fiedorowicz, Ewa; Teodorowicz, Małgorzata; Savelkoul, Huub F J

2017-09-09

Autism spectrum disorder (ASD) is a group of heterogeneous, behaviorally defined disorders whereby currently no biological markers are common to all affected individuals. A deregulated immune response may be contributing to the etiology of ASD. The active metabolite of vitamin D₃ has an immunoregulatory role mediated by binding to the vitamin D receptor (VDR) in monocyte, macrophages, and lymphocytes. The effects of vitamin D and interaction with the VDR may be influenced by polymorphism in the VDR gene. Genetic association of four different VDR polymorphisms (Apa-I, Bsm-I, Taq-I, Fok-I) associated with susceptibility to the development of autism in children was investigated. We uniquely found an association between the presence of the T allele at position Taq-I and presence of the a allele at position Apa-I of the VDR gene with decreased ASD incidence. There was also an association between female gender and the presence of the T allele. We found no statistical significant correlation between VDR single nucleotide polymorphisms (SNPs) and vitamin D₃ concentration in serum of ASD children. Genetic polymorphism in two SNP in VDR may be correlated with development of ASD symptoms by influencing functionality of vitamin D₃ metabolism, while vitamin D₃ levels were not significantly different between ASD and non-ASD children.

Leptin gene polymorphism in Indian Sahiwal cattle by single strand ...

African Journals Online (AJOL)

These leptin gene variants can be sequenced and screened in the entire population to develop single nucleotide polymorphisms (SNPs) for association studies with different productive and reproductive performances and marker assisted selection. Keywords: Leptin gene, PCR-SSCP, genetic variability, dairy cattle

An alternative LEU design for the FRM-II

International Nuclear Information System (INIS)

Hanan, N.A.; Mo, S.C.; Smith, R.S.; Matos, J.E.

1997-02-01

The Alternative LEU Design for the FRM-II proposed by the RERTR Program at Argonne National Laboratory (ANL) has a compact core consisting of a single fuel element that uses LEU silicide fuel with a uranium density of 4.5 g/cm[sup 3] and has a power level of 32 MW. Both the HEU design by the Technical University of Munich (TUM) and the alternative LEU design by ANL have the same fuel lifetime (50 days) and the same neutron flux performance (8 x 10[sup 14] n/cm[sup 2]/s in the reflector). LEU silicide fuel with 4.5 g/cm[sup 3] has been thoroughly tested and is fully-qualified, licensable, and available now for use in a high flux reactor such as the FRM-II. Computer models for the HEU and LEU designs have been exchanged between TUM and ANL and discrepancies have been resolved. The following issues are addressed: qualification of HEU and LEU silicide fuels, stability of the fuel plates, gamma heating in the heavy water reflector, a hypothetical accident involving the configuration of the reflector, a loss of primary coolant flow transient due to an interrupted power supply, the radiological consequences of larger fission product and plutonium inventories in the LEU core, and cost and schedule. Calculations were also done to address the possibility that new high density LEU fuels could be developed that would allow conversion of the TUM HEU design to LEU fuel. Based on the excellent results for the Alternative LEU Design that were obtained in these analyses, the RERTR Program concludes that all of the major technical issues regarding use of LEU fuel instead of HEU fuel in the FRM-II have been successfully resolved and that it is definitely feasible to use LEU fuel in the FRM-II without compromising the safety or performance of the facility

Association of inflammatory gene polymorphisms with ischemic stroke in a Chinese Han population

OpenAIRE

Zhao, Nan; Liu, Xin; Wang, Yongqin; Liu, Xiaoqiu; Li, Jiana; Yu, Litian; Ma, Liyuan; Wang, Shuyu; Zhang, Hongye; Liu, Lisheng; Zhao, Jingbo; Wang, Xingyu

2012-01-01

Abstract Background Inflammatory mechanisms are important in stroke risk, and genetic variations in components of the inflammatory response have been implicated as risk factors for stroke. We tested the inflammatory gene polymorphisms and their association with ischemic stroke in a Chinese Han population. Methods A total of 1,124 ischemic stroke cases and 1,163 controls were genotyped with inflammatory panel strips containing 51 selected inflammatory gene polymorphisms from 35 candidate genes...

No Association between Personality and Candidate Gene Polymorphisms in a Wild Bird Population.

Directory of Open Access Journals (Sweden)

Hannah A Edwards

Full Text Available Consistency of between-individual differences in behaviour or personality is a phenomenon in populations that can have ecological consequences and evolutionary potential. One way that behaviour can evolve is to have a genetic basis. Identifying the molecular genetic basis of personality could therefore provide insight into how and why such variation is maintained, particularly in natural populations. Previously identified candidate genes for personality in birds include the dopamine receptor D4 (DRD4, and serotonin transporter (SERT. Studies of wild bird populations have shown that exploratory and bold behaviours are associated with polymorphisms in both DRD4 and SERT. Here we tested for polymorphisms in DRD4 and SERT in the Seychelles warbler (Acrocephalus sechellensis population on Cousin Island, Seychelles, and then investigated correlations between personality and polymorphisms in these genes. We found no genetic variation in DRD4, but identified four polymorphisms in SERT that clustered into five haplotypes. There was no correlation between bold or exploratory behaviours and SERT polymorphisms/haplotypes. The null result was not due to lack of power, and indicates that there was no association between these behaviours and variation in the candidate genes tested in this population. These null findings provide important data to facilitate representative future meta-analyses on candidate personality genes.

Evaluation of ACE gene I/D polymorphism in Iranian elite athletes.

Science.gov (United States)

Shahmoradi, Somayeh; Ahmadalipour, Ali; Salehi, Mansoor

2014-01-01

Angiotensin converting enzyme (ACE) is an important gene, which is associated with the successful physical activity. The ACE gene has a major polymorphism (I/D) in intron 16 that determines its plasma and tissue levels. In this study, we aimed to determine whether there is an association between this polymorphism and sports performance in our studied population including elite athletes of different sports disciplines. We investigated allele frequency and genotype distribution of the ACE gene in 156 Iranian elite athletes compared to 163 healthy individuals. We also investigated this allele frequency between elite athletes in three functional groups of endurance, power, and mixed sports performances. DNA was extracted from peripheral blood, and polymerase chain reaction (PCR) method was performed on intron 16 of the ACE gene. The ACE genotype was determined for each subject. Statistical analysis was performed by SPSS 15, and results were analyzed by Chi-Square test. There was a significant difference in genotype distribution and allele frequency of the ACE gene in athletes and control group (P = 0.05, P = 0.03, respectively). There was also a significant difference in allele frequency of the ACE gene in 3 groups of athletes with different sports disciplines (P = 0.045). Proportion of the ACE gene D allele was greater in elite endurance athletes (37 high-distance cyclists) than two other groups. Findings of the present study demonstrated that there is an association between the ACE gene I/D polymorphism and sports performance in Iranian elite athletes.

Polymorphisms of Selected DNA Repair Genes and Lung Cancer in Chromium Exposure.

Science.gov (United States)

Halasova, E; Matakova, T; Skerenova, M; Krutakova, M; Slovakova, P; Dzian, A; Javorkova, S; Pec, M; Kypusova, K; Hamzik, J

2016-01-01

Chromium is a well-known mutagen and carcinogen involved in lung cancer development. DNA repair genes play an important role in the elimination of genetic changes caused by chromium exposure. In the present study, we investigated the polymorphisms of the following DNA repair genes: XRCC3, participating in the homologous recombination repair, and hMLH1 and hMSH2, functioning in the mismatch repair. We focused on the risk the polymorphisms present in the development of lung cancer regarding the exposure to chromium. We analyzed 106 individuals; 45 patients exposed to chromium with diagnosed lung cancer and 61 healthy controls. Genotypes were determined by a PCR-RFLP method. We unravelled a potential for increased risk of lung cancer development in the hMLH1 (rs1800734) AA genotype in the recessive model. In conclusion, gene polymorphisms in the DNA repair genes underscores the risk of lung cancer development in chromium exposed individuals.

Polymorphisms in miRNA genes and their involvement in autoimmune diseases susceptibility.

Science.gov (United States)

Latini, Andrea; Ciccacci, Cinzia; Novelli, Giuseppe; Borgiani, Paola

2017-08-01

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate the expression of multiple protein-encoding genes at the post-transcriptional level. MicroRNAs are involved in different pathways, such as cellular proliferation and differentiation, signal transduction and inflammation, and play crucial roles in the development of several diseases, such as cancer, diabetes, and cardiovascular diseases. They have recently been recognized to play a role also in the pathogenesis of autoimmune diseases. Although the majority of studies are focused on miRNA expression profiles investigation, a growing number of studies have been investigating the role of polymorphisms in miRNA genes in the autoimmune diseases development. Indeed, polymorphisms affecting the miRNA genes can modify the set of targets they regulate or the maturation efficiency. This review is aimed to give an overview about the available studies that have investigated the association of miRNA gene polymorphisms with the susceptibility to various autoimmune diseases and to their clinical phenotypes.

Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances

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Chiara De Luca

2015-01-01

Full Text Available Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI, namely, multiple chemical sensitivity (MCS, fibromyalgia (FM, and chronic fatigue syndrome (CFS. Given the reported association of nitric oxide synthase (NOS gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A −2.5 kb (CCTTTn as well as Ser608Leu and NOS3 −786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS, 89 FM/CFS, and 196 healthy subjects. Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 −786T>C polymorphisms. Interestingly, the NOS3 −786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A −2.5 kb (CCTTT11 allele represents a genetic determinant for FM/CFS, and the (CCTTT16 allele discriminates MCS from SMCS patients. Instead, the (CCTTT8 allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 −786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A −2.5 kb (CCTTTn polymorphism may be useful for differential diagnosis of various IEI.

Polymorphisms in inflammation pathway genes and endometrial cancer risk

Science.gov (United States)

Delahanty, Ryan J.; Xiang, Yong-Bing; Spurdle, Amanda; Beeghly-Fadiel, Alicia; Long, Jirong; Thompson, Deborah; Tomlinson, Ian; Yu, Herbert; Lambrechts, Diether; Dörk, Thilo; Goodman, Marc T.; Zheng, Ying; Salvesen, Helga B.; Bao, Ping-Ping; Amant, Frederic; Beckmann, Matthias W.; Coenegrachts, Lieve; Coosemans, An; Dubrowinskaja, Natalia; Dunning, Alison; Runnebaum, Ingo B.; Easton, Douglas; Ekici, Arif B.; Fasching, Peter A.; Halle, Mari K.; Hein, Alexander; Howarth, Kimberly; Gorman, Maggie; Kaydarova, Dylyara; Krakstad, Camilla; Lose, Felicity; Lu, Lingeng; Lurie, Galina; O’Mara, Tracy; Matsuno, Rayna K.; Pharoah, Paul; Risch, Harvey; Corssen, Madeleine; Trovik, Jone; Turmanov, Nurzhan; Wen, Wanqing; Lu, Wei; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou

2013-01-01

Background Experimental and epidemiological evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. Methods To investigate this hypothesis, a two-stage study was carried out to evaluate single nucleotide polymorphisms (SNPs) in inflammatory pathway genes in association with endometrial cancer risk. In stage 1, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage 1 SNPs significantly associated with endometrial cancer (PAsian- and European-ancestry samples. Conclusions These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact Statement This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis. PMID:23221126

DNA Repair Gene Polymorphism and the Risk of Mitral Chordae Tendineae Rupture

Directory of Open Access Journals (Sweden)

Aysel Kalayci Yigin

2015-01-01

Full Text Available Polymorphisms in Lys939Gln XPC gene may diminish DNA repair capacity, eventually increasing the risk of carcinogenesis. The aim of the present study was to evaluate the significance of polymorphism Lys939Gln in XPC gene in patients with mitral chordae tendinea rupture (MCTR. Twenty-one patients with MCTR and thirty-seven age and sex matched controls were enrolled in the study. Genotyping of XPC gene Lys939Gln polymorphism was carried out using polymerase chain reaction- (PCR- restriction fragment length polymorphism (RFLP. The frequencies of the heterozygote genotype (Lys/Gln-AC and homozygote genotype (Gln/Gln-CC were significantly different in MCTR as compared to control group, respectively (52.4% versus 43.2%, p=0.049; 38.15% versus 16.2%, p=0.018. Homozygote variant (Gln/Gln genotype was significantly associated with increased risk of MCTR (OR = 2.059; 95% CI: 1.097–3.863; p=0.018. Heterozygote variant (Lys/Gln genotype was also highly significantly associated with increased risk of MCTR (OR = 1.489; 95% CI: 1.041–2.129; p=0.049. The variant allele C was found to be significantly associated with MCTR (OR = 1.481; 95% CI: 1.101–1.992; p=0.011. This study has demonstrated the association of XPC gene Lys939Gln polymorphism with MCTR, which is significantly associated with increased risk of MCTR.

Angiotensinogen and ACE gene polymorphisms and risk of atrial fibrillation in the general population

DEFF Research Database (Denmark)

Ravn, Lasse Steen; Benn, Marianne; Nordestgaard, Børge

2008-01-01

Objectives The renin-angiotensin system may play a role in the pathogenesis of atrial fibrillation, and renin-angiotensin system blockers reduce the risk of atrial fibrillation. We hypothesized that polymorphisms in the angiotensinogen and angiotensin-converting enzyme (ACE) genes encoding proteins...... in this system predict risk of atrial fibrillation. Methods and results We genotyped 9235 individuals from the Danish general population, The Copenhagen City Heart Study, for the a-20c, g-6a, T174M, and M235T polymorphisms in the angiotensinogen gene and the insertion/deletion (I/D) polymorphism in the ACE gene...

Regional Brain Shrinkage over Two Years: Individual Differences and Effects of Pro-Inflammatory Genetic Polymorphisms

Science.gov (United States)

Persson, N.; Ghisletta, P.; Dahle, C.L.; Bender, A.R.; Yang, Y.; Yuan, P.; Daugherty, A.M.; Raz, N.

2014-01-01

We examined regional changes in brain volume in healthy adults (N = 167, age 19-79 years at baseline; N = 90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (HC), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the HC, CbH, In, OF, and the PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants mediated shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1βC-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFRC677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ε4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan. PMID:25264227

Clinical value of miR-198-5p in lung squamous cell carcinoma assessed using microarray and RT-qPCR.

Science.gov (United States)

Liang, Yue-Ya; Huang, Jia-Cheng; Tang, Rui-Xue; Chen, Wen-Jie; Chen, Peng; Cen, Wei-Luan; Shi, Ke; Gao, Li; Gao, Xiang; Liu, An-Gui; Peng, Xiao-Tong; Chen, Gang; Huang, Su-Ning; Fang, Ye-Ying; Gu, Yong-Yao

2018-02-02

To examine the clinical value of miR-198-5p in lung squamous cell carcinoma (LUSC). Gene Expression Omnibus (GEO) microarray datasets were used to explore the miR-198-5p expression and its diagnostic value in LUSC. Real-time reverse transcription quantitative polymerase chain reaction was used to evaluate the expression of miR-198-5p in 23 formalin-fixed, paraffin-embedded (FFPE) LUSC tissues and corresponding non-cancerous tissues. The correlation between miR-198-5p expression and clinic pathological features was assessed. Meanwhile, putative target messenger RNAs of miR-198-5p were identified based on the analysis of differentially expressed genes in the Cancer Genome Atlas (TCGA) and 12 miRNA prediction tools. Subsequently, the putative target genes were sent to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. MiR-198-5p was low expressed in LUSC tissues. The combined standard mean difference (SMD) values of miR-198-5p expression based on GEO datasets were - 0.30 (95% confidence interval (CI) - 0.54, - 0.06) and - 0.39 (95% CI - 0.83, 0.05) using fixed effect model and random effect model, respectively. The sensitivity and specificity were not sufficiently high, as the area under the curve (AUC) was 0.7749 (Q* = 0.7143) based on summarized receiver operating characteristic (SROC) curves constructed using GEO datasets. Based on the in-house RT-qPCR, miR-198-5p expression was 4.3826 ± 1.7660 in LUSC tissues and 4.4522 ± 1.8263 in adjacent normal tissues (P = 0.885). The expression of miR-198-5p was significantly higher in patients with early TNM stages (I-II) than that in cases with advanced TNM stages (III-IV) (5.4400 ± 1.5277 vs 3.5690 ± 1.5228, P = 0.008). Continuous variable-based meta-analysis of GEO and PCR data displayed the SMD values of - 0.26 (95% CI - 0.48, - 0.04) and - 0.34 (95% CI - 0.71, 0.04) based on fixed and random effect models, respectively. As for the diagnostic

Association of porcine UCP3 gene polymorphisms with fatness traits ...

African Journals Online (AJOL)

Administrator

2011-04-25

Apr 25, 2011 ... ... for fatness traits in pig. Polymorphism in UCP3 gene may change the function ... NM_214049) and human UCP3 gene DNA sequence (GenBank accession No. NC_000011). ..... Sleep, 29: 645-649. Zhao J, Li H, Kong X, ...

ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wenchao; Wang, Hui; Zhang, Wei [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Lv, Ruijuan [Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wang, Zhihao [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Geriatrics, Qilu Hospital of Shandong University, Jinan (China); Shang, Yuanyuan; Zhang, Yun; Zhong, Ming [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo; Tang, Mengxiong, E-mail: tangmengxiongsdu8@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China)

2013-08-15

Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients.

ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

International Nuclear Information System (INIS)

Zhang, Wenchao; Wang, Hui; Zhang, Wei; Lv, Ruijuan; Wang, Zhihao; Shang, Yuanyuan; Zhang, Yun; Zhong, Ming; Chen, Yuguo; Tang, Mengxiong

2013-01-01

Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients

[CCR5, CCR2, apoe, p53, ITGB3 and HFE gene polymorphism in Western Siberia long-livers].

Science.gov (United States)

Ivanoshchuk, D E; Mikhaĭlova, S V; Kulikov, I V; Maksimov, V N; Voevoda, M I; Romashchenko, A G

2012-01-01

In order to estimate the distribution of some polymorphisms for the CCR5, CCR2, apoE, p53, ITGB3, and HFE genes in Russian long-livers from Western Siberia, a sample of 271 individuals (range 90-105 years) was examined. It was demonstrated that carriage of the delta32 polymorphism for the CCR5 gene, V64/polymorphism for the CCR2 gene, e2/e3/e4 for the apoE gene, L33P for the ITGB3 gene, as well as H63D and S65C polymorphisms for the HFE gene does not influence on predisposition to the longevity; carriage of the 282 Y allele for the HFE gene negatively influences on the longevity; carriage of the heterozygous genotype for the R72P polymorphism for the p53 gene correlates with the longevity of elderly people.

Polymorphisms of the prion protein gene Arabi sheep breed in Iran ...

African Journals Online (AJOL)

Ovine scrapie is a neurodegenerative disease caused by polymorphisms of the prion protein gene (Prnp); especially the amino acid residue alterations at codons 136, 154, and 174, in sheep have been found to be associated with susceptibility to scrapie disease. We studied Prnp polymorphisms in local sheep of ...

Influence of correlation between HLA-G polymorphism and Interleukin-6 (IL6) gene expression on the risk of schizophrenia.

Science.gov (United States)

Shivakumar, Venkataram; Debnath, Monojit; Venugopal, Deepthi; Rajasekaran, Ashwini; Kalmady, Sunil V; Subbanna, Manjula; Narayanaswamy, Janardhanan C; Amaresha, Anekal C; Venkatasubramanian, Ganesan

2018-07-01

Converging evidence suggests important implications of immuno-inflammatory pathway in the risk and progression of schizophrenia. Prenatal infection resulting in maternal immune activation and developmental neuroinflammation reportedly increases the risk of schizophrenia in the offspring by generating pro-inflammatory cytokines including IL-6. However, it is not known how prenatal infection can induce immuno-inflammatory responses despite the presence of immuno-inhibitory Human Leukocyte Antigen-G (HLA-G) molecules. To address this, the present study was aimed at examining the correlation between 14 bp Insertion/Deletion (INDEL) polymorphism of HLA-G and IL-6 gene expression in schizophrenia patients. The 14 bp INDEL polymorphism was studied by PCR amplification/direct sequencing and IL-6 gene expression was quantified by using real-time RT-PCR in 56 schizophrenia patients and 99 healthy controls. We observed significantly low IL6 gene expression in the peripheral mononuclear cells (PBMCs) of schizophrenia patients (t = 3.8, p = .004) compared to the controls. In addition, schizophrenia patients carrying Del/Del genotype of HLA-G 14 bp INDEL exhibited significantly lower IL6 gene expression (t = 3.1; p = .004) than the Del/Ins as well as Ins/Ins carriers. Our findings suggest that presence of "high-expressor" HLA-G 14 bp Del/Del genotype in schizophrenia patients could attenuate IL-6 mediated inflammation in schizophrenia. Based on these findings it can be assumed that HLA-G and cytokine interactions might play an important role in the immunological underpinnings of schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association of oxidative stress gene polymorphisms with presbycusis.

Science.gov (United States)

Manche, Santoshi Kumari; Jangala, Madhavi; Putta, Padmavathi; Koralla, Raja Meganadh; Akka, Jyothy

2016-11-30

Presbycusis is characterised by etiopathological changes in the cochlea of the inner ear due to genetic and environmental factors and has a serious impact on quality of life. The present study was aimed to evaluate the role of oxidant stress gene polymorphisms in the development of presbycusis. 220 subjects with confirmed presbycusis from ENT specialists of MAA ENT hospital, Hyderabad, India from 2012 to 2014 were considered for the study. 270 age and sex matched controls were included in the study. Analysis of gene polymorphisms of SNPs cytochrome P450 1A1 (CYP1A1) 3801 T>C, 2455 A>G and 2453 A>C; glutathione S transferase (GST) T1 and M1; N-acetyl transferase (NAT2) 282 C>T and 857 G>A; uncoupled proteins (UCP1) (-3826) A>G and (UCP2) (866)G>A was carried out. Variations in the allelic and genotypic frequencies obtained were computed and analysed using appropriate statistical methods. The results of the study indicated that CYP1A1 gene polymorphism at 2453 C>A (adjusted OR: 1.59, 95% CI: 1.01-2.87) and 2455 A>G (adjusted OR: 1.87, 95% CI: 1.07-3.37), double null genotype of GSTM1 and GSTT1 (adjusted OR: 8.88, 95% CI: 4.10-19.19), NAT2 gene at C282T (adjusted OR: 1.77, 95% CI: 1.02-3.11) and G590 A (adjusted OR: 1.83, 95% CI 1.20-3.63) and UCP2 (-866) G>A (adjusted OR: 12.39; 95% CI: 6.51-23.56) showed increased risk for presbycusis while CYP1A1 at 3801 T>C and UCP1 (-3286) A>G exhibited no association. The haplotype combinations of T-G-A of CYP1A1 at 3801, 2455 and 2453 positions as well as T-A of NAT2*6 at 282 and 590 positions were found to contribute significant risk for the onset of presbycusis. Gene polymorphisms of CYP1A1 (A2455G, C2453A), NAT2*6 (C282T, G590 A), GST T1/M1 (double null genotype) and UCP2 (G-866 A) were found to contribute significant risk to presbycusis. Copyright © 2016 Elsevier B.V. All rights reserved.

The relation of serotonin-related gene and COMT gene polymorphisms with criminal behavior in schizophrenic disorder.

Science.gov (United States)

Koh, Kyung Bong; Choi, Eun Hee; Lee, Young-joon; Han, Mooyoung; Choi, Sang-Sup; Kim, So Won; Lee, Min Goo

2012-02-01

It has been suggested that patients with schizophrenia might be involved in criminal behavior, such as homicidal and violent behavior. However, the relationship between criminal behavior and genes in patients with schizophrenia has not been clearly elucidated. The objective of this study was to examine the relation between criminal behavior and serotonin-related gene or catechol-O-methyltransferase (COMT) gene polymorphisms in patients with schizophrenia. Serotonin-related and COMT polymorphic markers were assessed by using single nucleotide polymorphism (SNP) genotyping. Ninety-nine crime-related inpatients with schizophrenia (57 homicidal and 42 nonhomicidal violent) and 133 healthy subjects were enrolled between October 2005 and May 2008. Diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The genotype frequencies of tryptophan hydroxylase-1 (TPH1) A218C and COMT V158M were compared between groups. The TPH1 CC genotype had 2.7-fold higher odds of crime-related schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 2.69; 95% CI, 1.22 - 5.91; P = .01). In addition, the TPH1 CC genotype had 3.4-fold higher odds of homicidal schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 3.38; 95% CI, 1.40 - 8.18; P = .007). However, no significant differences were found in the frequencies of genotype of COMT polymorphism between criminal schizophrenics and healthy subjects, nor were any significant differences found between nonhomicidal schizophrenics and healthy subjects. These results indicate that the TPH1 CC recessive genotype is likely to be a genetic risk factor for criminal behavior, especially homicidal behavior in patients with schizophrenia. However, COMT gene polymorphisms were not associated with criminal behavior in schizophrenic patients. © Copyright 2012 Physicians Postgraduate Press, Inc.

Polymorphisms of Mannose-binding Lectin and Toll-like Receptors 2, 3, 4, 7 and 8 and the Risk of Respiratory Infections and Acute Otitis Media in Children.

Science.gov (United States)

Toivonen, Laura; Vuononvirta, Juho; Mertsola, Jussi; Waris, Matti; He, Qiushui; Peltola, Ville

2017-05-01

Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are important components of the innate immune system. We assessed the susceptibility of children with genetic variants in these factors to respiratory infections, rhinovirus infections and acute otitis media. In a prospective cohort study, blood samples from 381 Finnish children were analyzed for polymorphisms in MBL2 at codons 52, 54 and 57, TLR2 Arg753Gln, TLR3 Leu412Phe, TLR4 Asp299Gly, TLR7 Gln11Leu and TLR8 Leu651Leu. Children were followed up for respiratory infections until 24 months of age with daily diaries. Polymerase chain reaction and antigen tests were used for detection of respiratory viruses from nasal swabs. Children with MBL variant genotype had a mean of 59 days with symptoms of respiratory infection per year, compared with 49 days in those with wild-type (P = 0.01). TLR8 polymorphisms were associated with an increased risk and TLR7 polymorphisms with a decreased risk of recurrent rhinovirus infections (P = 0.02 for both). TLR2 polymorphisms were associated with recurrent acute otitis media (P = 0.02). MBL polymorphisms were associated with an increased and TLR7 polymorphisms with a decreased risk of rhinovirus-associated acute otitis media (P = 0.03 and P = 0.006, respectively). Genetic polymorphisms in MBL and TLRs promote susceptibility to or protection against respiratory infections. In addition to environmental factors, genetic variations may explain why some children are more prone to respiratory infections.

dPORE-miRNA: Polymorphic regulation of microRNA genes

KAUST Repository

Schmeier, Sebastian; Schaefer, Ulf; MacPherson, Cameron R.; Bajic, Vladimir B.

2011-01-01

Background: MicroRNAs (miRNAs) are short non-coding RNA molecules that act as post-transcriptional regulators and affect the regulation of protein-coding genes. Mostly transcribed by PolII, miRNA genes are regulated at the transcriptional level similarly to protein-coding genes. In this study we focus on human miRNAs. These miRNAs are involved in a variety of pathways and can affect many diseases. Our interest is on possible deregulation of the transcription initiation of the miRNA encoding genes, which is facilitated by variations in the genomic sequence of transcriptional control regions (promoters). Methodology: Our aim is to provide an online resource to facilitate the investigation of the potential effects of single nucleotide polymorphisms (SNPs) on miRNA gene regulation. We analyzed SNPs overlapped with predicted transcription factor binding sites (TFBSs) in promoters of miRNA genes. We also accounted for the creation of novel TFBSs due to polymorphisms not present in the reference genome. The resulting changes in the original TFBSs and potential creation of new TFBSs were incorporated into the Dragon Database of Polymorphic Regulation of miRNA genes (dPORE-miRNA). Conclusions: The dPORE-miRNA database enables researchers to explore potential effects of SNPs on the regulation of miRNAs. dPORE-miRNA can be interrogated with regards to: a/miRNAs (their targets, or involvement in diseases, or biological pathways), b/SNPs, or c/transcription factors. dPORE-miRNA can be accessed at http://cbrc.kaust.edu.sa/dpore and http://apps.sanbi.ac.za/dpore/. Its use is free for academic and non-profit users. © 2011 Schmeier et al.

dPORE-miRNA: Polymorphic regulation of microRNA genes

KAUST Repository

Schmeier, Sebastian

2011-02-04

Background: MicroRNAs (miRNAs) are short non-coding RNA molecules that act as post-transcriptional regulators and affect the regulation of protein-coding genes. Mostly transcribed by PolII, miRNA genes are regulated at the transcriptional level similarly to protein-coding genes. In this study we focus on human miRNAs. These miRNAs are involved in a variety of pathways and can affect many diseases. Our interest is on possible deregulation of the transcription initiation of the miRNA encoding genes, which is facilitated by variations in the genomic sequence of transcriptional control regions (promoters). Methodology: Our aim is to provide an online resource to facilitate the investigation of the potential effects of single nucleotide polymorphisms (SNPs) on miRNA gene regulation. We analyzed SNPs overlapped with predicted transcription factor binding sites (TFBSs) in promoters of miRNA genes. We also accounted for the creation of novel TFBSs due to polymorphisms not present in the reference genome. The resulting changes in the original TFBSs and potential creation of new TFBSs were incorporated into the Dragon Database of Polymorphic Regulation of miRNA genes (dPORE-miRNA). Conclusions: The dPORE-miRNA database enables researchers to explore potential effects of SNPs on the regulation of miRNAs. dPORE-miRNA can be interrogated with regards to: a/miRNAs (their targets, or involvement in diseases, or biological pathways), b/SNPs, or c/transcription factors. dPORE-miRNA can be accessed at http://cbrc.kaust.edu.sa/dpore and http://apps.sanbi.ac.za/dpore/. Its use is free for academic and non-profit users. © 2011 Schmeier et al.

Factor XIII Val34Leu is a genetic factor involved in the etiology of venous thrombosis

NARCIS (Netherlands)

Franco, R. F.; Reitsma, P. H.; Lourenço, D.; Maffei, F. H.; Morelli, V.; Tavella, M. H.; Araújo, A. G.; Piccinato, C. E.; Zago, M. A.

1999-01-01

A mutation in the factor XIII gene (FXIII Val34Leu) gene was recently reported to confer protection against myocardial infarction, but its relationship with venous thrombosis is unknown. In addition, a mutation in the 5'-untranslated region of the FXII gene (46 C->T) was identified which is

Association of IL-6 and MMP-3 gene polymorphisms with ...

Indian Academy of Sciences (India)

comprehensively and systematically performed this meta-analysis to detect whether the two gene polymorphisms are corre- .... control studies; (ii) 'failure to provide the genes' distribution details ..... biological activity of corresponding proteins such as IL-6 .... pathic scoliosis is related to inadequate calcium intake and weight.

Growth Hormone Gene Polymorphism in Two Iranian Native Fowls (Short Communication

Directory of Open Access Journals (Sweden)

Jafari A

1999-11-01

Full Text Available Biochemical polymorphism study is a method of determination of genetic variation. This variability could be a basis for selection and subsequent genetic improvement in farm animals. The polymorphism in the intron 1 of chicken growth hormone (cGH gene was investigated in the Iranian native fowls by using polymerase chain reaction (PCR-restriction fragment length polymorphism (RFLP method. The genomic DNA was extracted from 217 samples (129 samples from the native fowls of Isfahan province and 88 samples from the native fowls of Mazandaran province by using modified salting out technique. The DNA fragment of the growth hormone gene with 776 bp was amplified by PCR using specific primers. Then the PCR products were digested with MspI restriction enzyme and analyzed on 2.5% agarose gel. The allelic frequency of intron 1 locus for A1, A2 and A3 alleles in  Isfahan native fowls were 0.60, 0.21 and 0.19 and those in Mazandaran native  fowls were 0.28, 0.05 and 0.67, respectively. The results of current study indicated that the intron 1 of cGH is polymorphic in Iranian native fowls and could be exploited as a candidate gene for marker-assisted selection for growth-related traits.

Associations between STAT Gene Polymorphisms and Psoriasis in Northeastern China.

Science.gov (United States)

Zhou, Jing; Li, Yuzhen; Sun, Donglin

2017-01-01

Psoriasis is an autoimmune disease with genetic and environmental factors. Based on the roles of STATs (signaling transducers and activators of transcription) in autoimmune diseases, it is assumed STAT gene polymorphisms are associated with psoriasis. To study the association between STAT gene polymorphisms and psoriasis in the northeastern Chinese population. Eight single-nucleotide polymorphisms were genotyped: rs2293152, rs3816769, rs4796793, and rs744166 in STAT3, rs7574865 and rs3024866 in STAT4, and rs324011 and rs3024974 in STAT6, using SNaPshot methods. The genotype, allele, and haplotype frequencies were compared between 400 psoriasis patients and 398 healthy individuals in northeastern China. rs744166GG in STAT3 and rs7574865TT in STAT4 had higher frequencies in the case than the control group, suggesting these 2 genotypes increase the susceptibility to psoriasis (p < 0.05). Three haplotypes (H3, H6, and H7) were found to be associated with psoriasis in the study (p < 0.05). These results indicate a role of STAT genes in the pathogenesis of psoriasis. © 2017 S. Karger AG, Basel.

Extensive shared polymorphism at non-MHC immune genes in recently diverged North American prairie grouse

Science.gov (United States)

Minias, Piotr; Bateson, Zachary W.; Whittingham, Linda A.; Johnson, Jeff A.; Oyler-McCance, Sara J.; Dunn, Peter O.

2018-01-01

Gene polymorphisms shared between recently diverged species are thought to be widespread and most commonly reflect introgression from hybridization or retention of ancestral polymorphism through incomplete lineage sorting. Shared genetic diversity resulting from incomplete lineage sorting is usually maintained for a relatively short period of time, but under strong balancing selection it may persist for millions of years beyond species divergence (balanced trans-species polymorphism), as in the case of the major histocompatibility complex (MHC) genes. However, balancing selection is much less likely to act on non-MHC immune genes. The aim of this study was to investigate the patterns of shared polymorphism and selection at non-MHC immune genes in five grouse species from Centrocercus and Tympanuchus genera. For this purpose, we genotyped five non-MHC immune genes that do not interact directly with pathogens, but are involved in signaling and regulate immune cell growth. In contrast to previous studies with MHC, we found no evidence for balancing selection or balanced trans-species polymorphism among the non-MHC immune genes. No haplotypes were shared between genera and in most cases more similar allelic variants sorted by genus. Between species within genera, however, we found extensive shared polymorphism, which was most likely attributable to introgression or incomplete lineage sorting following recent divergence and large ancestral effective population size (i.e., weak genetic drift). Our study suggests that North American prairie grouse may have attained relatively low degree of reciprocal monophyly at nuclear loci and reinforces the rarity of balancing selection in non-MHC immune genes.

A meta-analysis of adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility

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Xiuju Chen

2016-01-01

Full Text Available Several studies have investigated the correlation between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk. However, the results were not conclusive with each other. Therefore, to overcome this obstacle, we performed this meta-analysis to further explicate the adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility. Case-control or cohort studies focused on adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk were electronic searched in the databases of Medline, Pubmed, Cochrane library, Excerpta Medica database(EMBASE and China National Knowledge Infrastructure (CNKI. All the potentially relevant studies were included in this meta-analysis. The association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke was expressed by odds ratio with its confidence interval. Publication bias has been assessed by begg’s funnel plot. All the analyses have been performed by Revman 5.1 statistical software. Finally, a total of six studies with 1,345 cases and 1,421 controls were included in this meta-analysis. Our results demonstrated that there was a significant association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk (p<0.05. People with G single nucleotide of adiponectin gene have the increased risk of developing ischemic stroke compared to T single nucleotide.

A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women.

Science.gov (United States)

Shaik, A P; Sultana, A; Bammidi, V K; Sampathirao, K; Jamil, K

2011-10-01

A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.

Polymorphism investigation of calpastatin gene in Zel sheep ...

African Journals Online (AJOL)

hosein

2012-02-14

Feb 14, 2012 ... Meat tenderness is an important quality characteristic for which consumers are interested. ... Key words: Calpastatin gene, polymorphism, Zel sheep, meat and polymerase chain reaction- ..... correlations for bovine postrigor calpastatin activity, intramuscular fat ... expression of the mRNA in skeletal muscle.

Cytokine Gene Polymorphisms in Egyptian Cases with Brain Tumors

International Nuclear Information System (INIS)

Badr El-Din, N.K.; Abdel-Hady, E.K.; Salem, F.K.; Settin, A.; ALI, N.

2009-01-01

Background: Cytokines are proposed to play important roles in brain tumor biology as well as neuro degeneration or impaired neuronal function. Objectives: This work aimed to check the association of polymorphisms of cytokine genes in Egyptian cases with brain tumors. Methods: This work included 45 cases affected by brain tumors diagnosed as 24 benign and 21 malignant. Their median age was 45 years, and they were 20 males and 25 females. These cases were taken randomly from the Neurosurgery Department of Mansoura University Hospital, Egypt. Case genotypes were compared to 98 healthy unrelated controls from the same locality. DNA was amplified using PCR utilizing sequence specific primers (SSP) for detection of polymorphisms related to TNF-a-308 (G/A), IL-10-1082 (G/A), IL-6-174 (G/C) and IL-1Ra (VNTR) genes. Results: Cases affected with benign brain tumors showed a significant higher frequency of IL-10-1082 A/A [odds ratio (OR=8.0), p<0.001] and IL-6-174 C/C (OR=6.3, p=0.002) homozygous genotypes as compared to controls. Malignant cases, on the other hand, showed significantly higher frequency of IL-6-174 C/C (OR =4.8, p=0.002) homozygous genotype and TNF-a-308 A/A (OR=4.9, p<0.001) homozygous genotype when compared to controls. In the meantime, all cases showed no significant difference regarding the distribution of IL-1Ra VNTR genotype polymorphism compared to controls. Conclusions: Cytokine gene polymorphisms showed a pattern of association with brain tumors which may have potential impact on family counseling and disease management.

Relationship between IL-10 gene -819C/T polymorphism and the ...

African Journals Online (AJOL)

Background: The -819C/T polymorphism in interleukin 10 (IL-10) gene has been reported to be associated with inflammatory bowel disease (IBD) ,but the previous results are conflicting. Materials and methods: The present study aimed at investigating the association between this polymorphism and risk of IBD using a ...

Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome

DEFF Research Database (Denmark)

Oskari Kilpeläinen, Tuomas; Lakka, Timo A; Laaksonen, David E

2008-01-01

Single nucleotide polymorphisms (SNPs) in the ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL genes were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D) in the Finnish Diabetes Prevention Study (DPS). In this study, we determined whether...... on the conversion to T2D was found. The Leu72Met (rs696217) polymorphism in GHRL modified the effect of moderate-to-vigorous PA on changes in weight and waist circumference, the -501A/C (rs26802) polymorphism in GHRL modified the effect of total and moderate-to-vigorous PA on change in high-density lipoprotein...... polymorphisms in these genes modified the effect of changes in physical activity (PA) on the risk of T2D in the DPS. Moreover, we assessed whether the polymorphisms modified the effect of changes in PA on changes in measures of body fat, serum lipids, and blood pressure during the first year of the follow...

Association between genetic polymorphisms in the human interleukin-7 receptor alpha-chain and inhalation allergy

DEFF Research Database (Denmark)

Shamim, Z; Müller, K; Svejgaard, A

2007-01-01

Thymic stromal-derived lymphopoietin (TSLP) and interleukin-7 share a common receptor chain, IL-7Ralpha. IL-7 is involved in T-cell homeostasis, and TSLP induces production of pro-allergic cytokines. The gene encoding the IL-7Ralpha chain is polymorphic, and investigation of inhalation allergic p...

Matrix metalloproteinase gene polymorphisms in patients with coronary artery disease

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Vanessa L.N. Dalepiane

2007-01-01

Full Text Available Matrix metalloproteinases (MMPs play an important role in the pathogenesis of atherosclerosis, the pathology underlying the majority of coronary artery disease (CAD. In this study we tested the hypothesis that polymorphic variation in the MMP genes influences the risk of developing atherosclerosis. We analyzed functional polymorphisms in the promoter of the MMP-1, MMP-3, MMP-9 and MMP-12 genes in 183 Brazilian Caucasian individuals submitted to coronary angiography, of which 67 (37% had normal coronary arteries (control group and 116 (63% had CAD (CAD patient group. The -1607 1G/2G MMP-1, -1171 5A/6A MMP-3, -1562 C/T MMP-9, -82 A/G MMP-12 polymorphisms were analyzed by PCR followed by restriction digestion. No significant differences were observed in allele frequencies between the CAD patients and controls. Haplotype analysis showed no differences between the CAD patients and controls. There was a significant difference in the severity of CAD, as assessed by the number of diseased vessels, in MMP-1 1G/1G homozygous individuals and in those homozygous for the 6A allele of the MMP-3 polymorphism. However, multivariate analysis showed that diabetes mellitus was the only variable independently associated with CAD severity. Our findings indicated that MMP polymorphisms have no significant impact on the risk and severity of CAD.

Activation of a synapse weakening pathway by human Val66 but not Met66 pro-brain-derived neurotrophic factor (proBDNF)

Science.gov (United States)

Kailainathan, Sumangali; Piers, Thomas M.; Yi, Jee Hyun; Choi, Seongmin; Fahey, Mark S.; Borger, Eva; Gunn-Moore, Frank J.; O’Neill, Laurie; Lever, Michael; Whitcomb, Daniel J.; Cho, Kwangwook; Allen, Shelley J.

2016-01-01

This study describes a fundamental functional difference between the two main polymorphisms of the pro-form of brain-derived neurotrophic factor (proBDNF), providing an explanation as to why these forms have such different age-related neurological outcomes. Healthy young carriers of the Met66 form (present in ∼30% Caucasians) have reduced hippocampal volume and impaired hippocampal-dependent memory function, yet the same polymorphic population shows enhanced cognitive recovery after traumatic brain injury, delayed cognitive dysfunction during aging, and lower risk of late-onset Alzheimer’s disease (AD) compared to those with the more common Val66 polymorphism. To examine the differences between the protein polymorphisms in structure, kinetics of binding to proBDNF receptors and in vitro function, we generated purified cleavage-resistant human variants. Intriguingly, we found no statistical differences in those characteristics. As anticipated, exogenous application of proBDNF Val66 to rat hippocampal slices dysregulated synaptic plasticity, inhibiting long-term potentiation (LTP) and facilitating long-term depression (LTD). We subsequently observed that this occurred via the glycogen synthase kinase 3β (GSK3β) activation pathway. However, surprisingly, we found that Met66 had no such effects on either LTP or LTD. These novel findings suggest that, unlike Val66, the Met66 variant does not facilitate synapse weakening signaling, perhaps accounting for its protective effects with aging. PMID:26687096

Polymorphisms in Genes Coding for Cytokines, Mannose-Binding Lectin, Collagen Metabolism and Thrombophilia in Women with Cervical Insufficiency

DEFF Research Database (Denmark)

Sundtoft, Iben; Uldbjerg, Niels; Steffensen, Rudi

2015-01-01

OBJECTIVE: To study the association between cervical insufficiency and single nucleotide polymorphisms in seven genes coding for pro- and anti-inflammatory cytokine-related factors, mannose-binding lectin 2 (MBL2), collagen1α1 (COL1A1), factor II and factor V Leiden genes. METHODS: In a case......-control study, potential maternal biomarkers for cervical insufficiency were investigated in 30 women with a history of second-trimester miscarriage or preterm birth due to cervical insufficiency and in 70 control women. RESULTS: Homozygous carriers of the interleukin 6 (IL6) -174 genotype GG had an odds ratio...... (OR) of 3.1 [95% confidence interval (95% CI) 1.3-7.4, p = 0.01] and MBL2 genotypes coding for low or intermediate levels of plasma MBL had an OR of 3.3 (95% CI 1.2-9.0, p = 0.01) for cervical insufficiency compared with controls. Serum MBL levels were lower in women with cervical insufficiency than...

Polymorphisms within the FANCA gene associate with premature ovarian failure in Korean women.

Science.gov (United States)

Pyun, Jung-A; Kim, Sunshin; Cha, Dong Hyun; Kwack, KyuBum

2014-05-01

This study investigated whether polymorphisms within the Fanconi anemia complementation group A (FANCA) gene contribute to the increased risk of premature ovarian failure (POF) in Korean women. Ninety-eight women with POF and 218 controls participated in this study. Genomic DNA from peripheral blood was isolated, and GoldenGate genotyping assay was used to identify single nucleotide polymorphisms (SNPs) within the FANCA gene. Two significant SNPs (rs1006547 and rs2239359; P FANCA gene may increase the risk for POF in Korean women.

Polymorphism in leptin receptor gene was associated with obesity in ...

African Journals Online (AJOL)

The mutation in leptin receptor (LEPR) gene causes splicing abnormality that resulted in truncated receptor, aberrant signal transduction, leptin resistance, and obesity. This study aims to determine the association of LEPR gene polymorphisms, rs1137100 and rs1137101, on phenotype and leptin level between obese and ...

Codon 201Gly Polymorphic Type of the DCC Gene is Related to Disseminated Neuroblastoma

Directory of Open Access Journals (Sweden)

Xiao-Tang Kong

2001-01-01

Full Text Available The deleted in colorectal carcinoma (DCC gene is a potential tumor- suppressor gene on chromosome 18821.3. The relatively high frequency of loss of heterozygosity (LOH and loss of expression of this gene in neuroblastoma, especially in the advanced stages, imply the possibility of involvement of the DCC gene in progression of neuroblastoma. However, only few typical mutations have been identified in this gene, indicating that other possible mechanisms for the inactivation of this gene may exist. A polymorphic change (Arg to Gly at DCC codon 201 is related to advanced colorectal carcinoma and increases in the tumors with absent DCC protein expression. In order to understand whether this change is associated with the development or progression of neuroblastoma, we investigated codon 201 polymorphism of the DCC gene in 102 primary neuroblastomas by polymerase chain reaction single-strand conformation polymorphism. We found no missense or nonsense mutations, but a polymorphic change from CGA (Arg to GGA (Gly at codon 201 resulting in three types of polymorphism: codon 201Gly type, codon 201Arg/Gly type, and codon 201Arg type. The codon 201Gly type occurred more frequently in disseminated (stages IV and IVs neuroblastomas (72% than in localized (stages I, II, and III tumors (48% (P=.035, and normal controls (38% (P=.024. In addition, the codon 201Gly type was significantly more common in tumors found clinically (65% than in those found by mass screening (35% (P=.002. The results suggested that the codon 201Gly type of the DCC gene might be associated with a higher risk of disseminating neuroblastoma.

Interleukin gene polymorphisms in Chinese Han population with breast cancer, a case-control study.

Science.gov (United States)

Zuo, Xiaoxiao; Li, Miao; Yang, Ya; Liang, Tiansong; Yang, Hongyao; Zhao, Xinhan; Yang, Daoke

2018-04-06

Cytokines are known as important regulators of the cancer involved in inflammatory and immunological responses. This fact and plethora of gene polymorphism data prompted us to investigate IL1 gene polymorphisms in breast cancer (BC) patients. Totally, 530 patients with BC and 628 healthy control women were studied. The genetic polymorphisms for IL1 were analyzed by Massarray Sequencing method. Three single nucleotide polymorphisms (SNPs) identified in IL1B, IL1R1 gene are thought to influence breast cancer risk. The results of the association between IL-1B, IL1R1 polymorphisms and breast cancer risk have significant. We found that the variant TT genotype of rs10490571 was associated with a significantly increased breast cancer risk (TT vs. CC: OR = 2.82, 95% CI = 1.12-7.08, P = 0.047 for the codominant model). For rs16944 (AG vs. GG: OR = 0.60, 95% CI = 0.41-0.90, P = 0.034 for the codominant model) and rs1143623 (CG vs. CC: OR = 0.65, 95% CI = 0.45-0.94, P = 0.023 for the codominant model) have significant associations were found in genetic models. In conclusion, the present analysis suggests a correlation of polymorphic markers within the IL-1 gene locus with the risk in developing breast cancer. Taken together with our finding that IL1B, IL1R1 gene three SNP are also associated with the risk for the disease, we suggest that inflammation via innate and adaptive immunity contributes to multifactorial hereditary predisposition to pathogenesis of the breast cancer.

Effects of bovine prolactin gene polymorphism within exon 4 on milk ...

African Journals Online (AJOL)

In this study, polymorphism of prolactin gene was analyzed as a candidate gene responsible for variation and genetic trends in milk yield and composition traits. Genomic DNAs were extracted from 268 semen samples belonged to Iranian Holstein bulls. Genotyping for the prolactin gene using PCRRFLP technique and RsaI ...

Association of luteinizing hormone chorionic gonadotropin receptor gene polymorphism (rs2293275) with polycystic ovarian syndrome.

Science.gov (United States)

Thathapudi, Sujatha; Kodati, Vijayalakshmi; Erukkambattu, Jayashankar; Addepally, Uma; Qurratulain, Hasan

2015-03-01

Polycystic ovaries and irregular menstruation/anovulation are important diagnostic criteria along with hyperandrogenism as per the Androgen Excess Society-2006 criteria for polycystic ovarian syndrome (PCOS). In the etiopathogenesis of PCOS, one of the candidate genes causing ovarian failure is the luteinizing hormone (LH) chorionic gonadotropin hormone receptor (LHCGR). Our aim was to study the association of LHCGR polymorphism (rs2293275) with PCOS in our study population. Genetic case-control study from multiple gynecological centers from Hyderabad, a cosmopolitan city in South India. The study involved 204 women with PCOS and 204 healthy, sex-, and age-matched controls. Anthropometric and biochemical profiles were taken in a well-designed pro forma. Isolation of deoxyribonucleic acid (DNA) and genotype analysis were done for the entire study population using the polymerase chain reaction-restriction fragment length polymorphism method followed by 12% polyacrylamide gel electrophoresis. In this study, we have demonstrated an association between LHCGR (rs2293275) polymorphism and PCOS. The frequency of the G allele was 0.60 in PCOS and 0.49 in controls (odds ratio [OR] 1.531, confidence interval [CI] 1.16-2.01, and p-value=0.0026), which indicates that the G allele is associated with PCOS in our population. The GG genotype conferred a significant risk of developing PCOS (OR 3.36, CI 1.96-5.75, and p-value<0.0001). We found a significant association of the GG allele with body-mass index, waist to hip ratio, insulin resistance, LH, and LH/follicle-stimulating hormone (FSH) ratio in PCOS when compared with controls. The AA allele showed high basal FSH levels. This study suggests that LHCGR (rs2293275) polymorphism is associated with PCOS and could be used as a relevant molecular marker to identify women with the risk of developing PCOS in our population and may provide an understanding about the etiology of PCOS.

Genetic association between polymorphism of mdm2 gene and symptoms and pathological types of NSCLC

International Nuclear Information System (INIS)

Liu Xiaolan; Wang Weili; Zhang Xueying; Hao Ming; Liu Linlin; Wu Zhenfeng; Jiang Hongwei

2008-01-01

Objective: To investigate the genetic association between polymorphism of mdm2 gene and symptoms and pathological types of non-small cell lung cancer (NSCLC). Methods: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used to identify mdm2 genotypes. The Pearson Chi square test and Woolf statistic method were used to analyze the relative risk and 95% confidence interval (CI) in order to find the genetic association between polymorphism of mdm2 gene and symptoms and pathological types of NSCLC. Results: In the SNP rs1196337 (a G to A base change) AA genotype showed association with cough of NSCLC (P<0.05). Conclusion: The polymorphism of mdm2 gene may be associated with symptom as cough of NSCLC. (authors)

Influence of leukotriene gene polymorphisms on chronic rhinosinusitis

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Duval Melanie

2008-03-01

Full Text Available Abstract Background Chronic rhinosinusitis (CRS is increasingly viewed as an inflammatory condition of the sinonasal mucosa interacting with bacteria and/or fungi. However, factors conferring susceptibility to disease remain unknown. Advances in genomics offer powerful tools to explore this disorder. The goal of this study was to evaluate the effect of single nucleotide polymorphisms (SNP on CRS in a panel of genes related to cysteinyl leukotriene metabolism. Methods Severe cases of CRS and postal code match controls were recruited prospectively. A total of 206 cases and 200 controls were available for the present study. Using a candidate gene approach, five genes related to cysteinyl leukotriene metabolism were assessed. For each gene, we selected the maximally informative set of common SNPs (tagSNPs using the European-derived (CEU HapMap dataset. These SNPs are in arachidonate 5-lipoxygenase (ALOX5, arachidonate 5-lipoxygenase-activating protein (ALOX5AP, leukotriene C4 synthase (LTC4S, cysteinyl leukotriene receptor 1 (CYSLTR1 and cysteinyl leukotriene receptor 2 (CYSLTR2 genes. Results A total of 59 SNPs were genotyped to capture the common genetic variations within these genes. Three SNPs located within the ALOX5, CYSLTR1 and ALOX5AP genes reached the nominal p-value threshold (p Conclusion While these initial results do not support that polymorphsims in genes assessed involved in the leukotriene pathways are contributing to the pathogenesis of CRS, this initial study was not powered to detect polymorphisms with relative risk of 2.0 or less, where we could expect many gene effects for complex diseases to occur. Thus, despite this lack of significant association noted in this study, we believe that validation with external populations and the use of better-powered studies in the future may allow more conclusive findings.

Multidrug resistance 1 gene polymorphisms may determine Crohn's disease behavior in patients from Rio de Janeiro

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Ana Teresa P. Carvalho

2014-01-01

Full Text Available OBJECTIVES: Conflicting data from studies on the potential role of multidrug resistance 1 gene polymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 gene polymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro. METHODS: We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 gene polymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations. RESULTS: No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (p = 0.047. A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; p = 0.009, whereas no association was found with penetrating behavior (OR: 0.33; p = 0.094. In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; p = 0.010. However, no significant association was found between multidrug resistance 1 gene polymorphisms and UC subphenotypic categories. CONCLUSION: The multidrug resistance 1 gene polymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles for the multidrug resistance 1 gene in regulating gut

Genetic polymorphisms at the leptin receptor gene in three beef cattle breeds

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Sabrina E.M. Almeida

2008-01-01

Full Text Available The genetic diversity of a single nucleotide polymorphism (SNP at the exon 20 (T945M of the leptin receptor gene (LEPR and of three short tandem repeats (STRs BM7225, BMS694, and BMS2145 linked to LEPR was investigated in three beef cattle herds (Brangus Ibagé, Charolais, and Aberdeen Angus. A cheap and effective new method to analyze the T945M polymorphism in cattle populations was developed and the possible role of these polymorphisms in reproduction and weight gain of postpartum cows was evaluated. High levels of genetic diversity were observed with the average heterozygosity of STRs ranging from 0.71 to 0.81. No significant association was detected between LEPR markers and reproductive parameters or daily weight gain. These negative results suggest that the LEPR gene polymorphisms, at least those herein described, do not influence postpartum cows production.

Relationship of interleukin-1B gene promoter region polymorphism with Helicobacter pylori infection and gastritis.

Science.gov (United States)

Ramis, Ivy Bastos; Vianna, Júlia Silveira; Halicki, Priscila Cristina Bartolomeu; Lara, Caroline; Tadiotto, Thássia Fernanda; da Silva Maciel, João Batista; Gonçalves, Carla Vitola; von Groll, Andrea; Dellagostin, Odir Antônio; da Silva, Pedro Eduardo Almeida

2015-09-29

Helicobacter pylori infection is associated with gastritis, peptic ulcer disease and gastric carcinoma. The severity of damage is determined by the interplay between environmental/behavioral factors, bacterial pathogenicity genes and host genetic polymorphisms that can influence the secretion levels of inflammatory cytokines. Accordingly, this study aimed to identify polymorphisms in the IL-1B and IL-1RN genes and their associations with H. pylori infection, cagA gene of H. pylori, and gastroduodenal diseases. Gastric biopsy samples from 151 patients infected with H. pylori and 76 uninfected individuals were analyzed. H. pylori infection was diagnosed by histology and PCR. Polymorphisms at positions -511, -31 and +3954 of the IL-1B gene were detected by PCR-RFLP, and an analysis of the VNTR polymorphism of the IL-1RN gene was performed by PCR. It was observed that the presence of the T/T genotype at position -511 and the C/C genotype at position -31 were associated with H. pylori infection and with an increased risk of gastritis in H. pylori-positive patients. Additionally, strains from patients H. pylori-positive carrying the cagA gene was significantly related with the T/T genotype at position -511 of IL-1B.  No association of polymorphisms at position +3954 of IL-1B and in the IL-1RN with H. pylori infection and with risk of severe gastric diseases was found. We demonstrated that polymorphisms in the promoter region of the IL-1B gene (at positions -511 and -31) are associated with an enhanced risk of H. pylori infection as well as gastritis in H. pylori-positive patients.

Association study of interferon gamma (IFN-γ) +874T/A gene polymorphism in patients with paranoid schizophrenia.

Science.gov (United States)

Paul-Samojedny, Monika; Owczarek, Aleksander; Suchanek, Renata; Kowalczyk, Malgorzata; Fila-Danilow, Anna; Borkowska, Paulina; Kucia, Krzysztof; Kowalski, Jan

2011-03-01

Schizophrenia is a multifactorial disease with changes affecting the immune system. Dysregulation of the cytokine network in schizophrenia has been well documented. Such changes may occur due to disturbances in cytokine levels that are linked to polymorphisms of cytokine genes. However, research in the role of cytokine gene polymorphisms in schizophrenia has been surprisingly scanty. The aim of this study was to identify, in a case control study, whether polymorphism of IFN-γ gene is a risk factor for the development of paranoid schizophrenia. To the best of our knowledge, this is the first study that examines the association between the IFN-γ gene polymorphism and psychopathological symptoms in patients with paranoid schizophrenia. Polymorphism of IFN-γ (+874T/A, rs 62559044) in schizophrenic patients (n=179), as well as healthy individuals (n=196), both Polish residents, was genotyped using AS-PCR method. Of note, when analyzing the results, we took into consideration the gender of studied individuals. Surprisingly, a single-nucleotide polymorphism in the first intron of the IFN-γ gene was found to be associated with paranoid schizophrenia in males, but not in females. The presence of allele A at position +874 in the IFN-γ gene correlates with 1.66-fold higher risk of paranoid schizophrenia development in males. Differences in the genotypes may have an important role in determining the level of I gene transcription. Because other polymorphisms have been demonstrated to influence IFN-γ transcription, further analysis is necessary to clarify the role of this gene in the pathogenesis of paranoid schizophrenia.

FEATURES OF THE CLINICAL SIGNIFICANCE OF POLYMORPHIC VARIANTS OF ENOS AND AGTR2 GENES IN PATIENTS WITH CAD

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A. L. Khokhlov

2016-01-01

Full Text Available Coronary heart disease (CHD is a major cause of mortality. Morphological substrate of CHD in most cases is atherosclerosis, which is based on structural genes polymorphism eNOS and AGTR2. The aim of the study was to study the prevalence of eNOS and AGTR2 genes in patients with coronary artery disease and the association of these genes with coronary heart disease. The study involved 187 patients aged 36 to 86 years (62,2±11,2 with different forms of CHD: stable and unstable angina, myocardial infarction and 45 people without CHD. Determination of gene polymorphisms was performed by real-time PCR analyzer of nucleic acids IQ 5 Bio-Rad. Statistical analysis was performed using Statistica 10.0. The study revealed a significant difference between the incidence of homozygous AA allelic variant gene AGTR2 group of patients with myocardial infarction and the comparison group; polymorphic variant AA AGTR2 gene is associated with earlier onset of coronary artery disease; It found that carriers of the polymorphic variant gene GA AGTR2 beginning statistically CHD occurred significantly later than in carriers of alleles GG and AA; age CHD debut TT allele carriers of the eNOS gene is associated with an earlier onset of the disease and statistically significantly different from the age of first CHD in carriers of alleles of polymorphic variants of GG and GT; revealed a positive correlation between the polymorphic allele AGTR2 gene with the presence of arterial hypertension in patients with coronary artery disease; It determined that the T allele carriers of the polymorphic gene eNOS is associated more early onset of hypertension, found the association of the polymorphic allele gene AGTR2 the need to use higher doses of ACE inhibitor — perindopril.

Interleukin Gene Polymorphisms and Susceptibility to HIV Infection

Indian Academy of Sciences (India)

Chrysa

vaccines, and with almost 36.7 million HIV-infected individuals worldwide .... The allelic and genotypic distribution of the IL genes SNPs are presented in .... polymorphism using the genetic model-free bivariate approach produced, as in ... Through its immuno-inhibitory and anti-inflammatory activities and, in particular, by.

[Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetics].

Science.gov (United States)

Olmos, P; Acosta, A M; Schiaffino, R; Díaz, R; Alvarado, D; O'Brien, A; Muñoz, X; Arriagada, P; Claro, J C; Vega, R; Vollrath, V; Velasco, S; Emmerich, M; Maiz, A

1999-04-01

Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. A random sample of 27 NIDDM, aged 68.1 +/- 10.6 years, with a mean diabetes duration of 20.7 +/- 4.8 years and a mean glycosilated hemoglobin of 10.6 +/- 1.6%, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5' end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p = 0.047). Both groups had similar glycosilated hemoglobin (11.7 +/- 0.2 and 10.5 +/- 1.6% respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5' end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate.

Metabolism and gene polymorphisms of the folate pathway in Brazilian women with history of recurrent abortion.

Science.gov (United States)

Boas, Wendell Vilas; Gonçalves, Rozana Oliveira; Costa, Olívia Lúcia Nunes; Goncalves, Marilda Souza

2015-02-01

To investigate the association between polymorphisms in genes that encode enzymes involved in folate- and vitamin B12-dependent homocysteine metabolism and recurrent spontaneous abortion (RSA). We investigated the C677T and A1298C polymorphisms of the methylenetetrahydrofalate reductase gene (MTHFR), the A2756G polymorphism of the methionine synthase gene (MS) and the 844ins68 insertion of the cystathionine beta synthetase gene (CBS). The PCR technique followed by RFLP was used to assess the polymorphisms; the serum levels of homocysteine, vitamin B12 and folate were investigated by chemiluminescence. The EPI Info Software version 6.04 was used for statistical analysis. Parametric variables were compared by Student's t-test and nonparametric variables by the Wilcoxon rank sum test. The frequencies of gene polymorphisms in 89 women with a history of idiopathic recurrent miscarriage and 150 controls were 19.1 and 19.6% for the C677T, insertion, 20.8 and 26% for the A1298C insertion, 14.2 and 21.9% for the A2756G insertion, and 16.4 and 18% for the 844ins68 insertion, respectively. There were no significant differences between case and control groups in any of the gene polymorphisms investigated. However, the frequency of the 844ins68 insertion in the CBS gene was higher among women with a history of loss during the third trimester of pregnancy (p=0.003). Serum homocysteine, vitamin B12 and folate levels id not differ between the polymorphisms studied in the case and control groups. However, linear regression analysis showed a dependence of serum folate levels on the maintenance of tHcy levels. The investigated gene polymorphisms and serum homocysteine, vitamin B12 and folate levels were not associated with idiopathic recurrent miscarriage in the present study. Further investigations are needed in order to confirm the role of the CBS 844ins68 insertion in recurrent miscarriage.

[Association of IL-1β-511T gene rs16944 polymorphism with febrile seizures].

Science.gov (United States)

Ren, Xiao-Tun; Sun, Su-Zhen; Liu, Fang; Wang, Xiao-Ming

2014-02-01

Despite substantial research efforts worldwide, the role of inflammatory cytokine IL-1β in the onset of febrile seizures (FS) remains controversial. The aim of this study was to assess the relationship between rs16944 polymorphism of the IL-1β-511T gene and occurrence of simple FS in a sample of Han children in northern China. The IL-1β-511T gene rs16944 was genotyped by SNaPshot SNP technique in 141 FS children and 130 healthy control subjects. The genotypic and allelic frequencies in the two groups were comparatively analyzed. There were no significant differences in genotypic and allelic frequencies of rs16944 polymorphism of the IL-1β-511T gene between FS patients and control subjects (P>0.05).When the clinical data on A/A, A/G and G/G genotypes of the rs16944 polymorphism in FS patients, there was statistically significant difference in age of first onset (χ(2)=19.491, Prs16944 polymorphism of the IL-1β-511T gene and the incidence of FS in Han children in Northern China. However, the differences in genotypes of this polymorphism might be associated with pathogenesis and prognosis of simple FS in the population studied.

[Association of muscle segment homeobox gene 1 polymorphisms with nonsyndromic cleft lip with or without cleft palate].

Science.gov (United States)

Zhang, Li; Tang, Jun-Ling; Liang, Shang-Zheng

2008-06-01

Muscle segment homeobox gene (MSX)1 has been proposed as a gene in which mutations may contribute to nonsyndromic cleft lip with or without cleft palate (NSCL/P). To study MSX1 polymorphisms in NSCL/ P by means of polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP), and investigate the association of MSX1 exons 1 polymorphisms with NSCL/P. DNA were extracted from blood samples from NSCL/P and unrelated normal subjects. Genome DNA from peripheral leukocyte with these blood samples were extracted, which was used as template to amplify desired gene fragment of MSX1 exons 1 by means of polymerase chain reaction (PCR). The PCR products were examined by single-strand conformation polymorphism (SSCP). The MSX1 exons 1 polymorphisms were examined by sequencing if mutations were found. MSX1 genes of exon 1 mutation was not been found in the NSCL/P and unrelated normal subjects by SSCP. No correlation between MSX1 exon 1 and NSCL/P was found. MSX1 exon 1 may not be a key gene (susceptibility gene) in NSCL/P.

GGC and StuI polymorphism on the androgen receptor gene in endometrial cancer patients

International Nuclear Information System (INIS)

Sasaki, Masahiro; Karube, Akihiro; Karube, Yuko; Watari, Michiko; Sakuragi, Noriaki; Fujimoto, Seiichiro; Dahiya, Rajvir

2005-01-01

Androgens have an anti-proliferative effect on endometrial cells. Human androgen receptor (AR) gene contains two polymorphic short tandem repeats of GGC and CAG, and a single-nucleotide polymorphism on exon 1 that is recognized by the restriction enzyme, StuI. Prior studies have shown that the lengths of the CAG repeat are inversely and linearly related to AR activity and associated with endometrial cancer. However, little is known about the GGC repeat and the StuI polymorphism of the AR gene. Thus, we investigated whether these AR polymorphisms are risk factors for endometrial cancer. To test this hypothesis, the genetic distributions of these polymorphisms were investigated in blood samples from endometrial cancer patients and healthy controls. The allelic and genotyping profiles were analyzed by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and direct DNA sequencing, and analyzed statistically. The GGC repeat was significantly longer in endometrial cancer patients as compared to normal healthy controls. In general, an increased risk of endometrial cancer was found with increasing GGC repeat. The relative risk for the 17 GGC repeat was greater than 4, as compared to controls. However, the StuI polymorphism was not significantly different between patients and controls. The findings suggest that increased numbers of GGC repeat on the AR gene may be a risk factor for endometrial cancer

[Expression of plant antimicrobial peptide pro-SmAMP2 gene increases resistance of transgenic potato plants to Alternaria and Fusarium pathogens].

Science.gov (United States)

Vetchinkina, E M; Komakhina, V V; Vysotskii, D A; Zaitsev, D V; Smirnov, A N; Babakov, A V; Komakhin, R A

2016-09-01

The chickweed (Stellaria media L.) pro-SmAMP2 gene encodes the hevein-like peptides that have in vitro antimicrobial activity against certain harmful microorganisms. These peptides play an important role in protecting the chickweed plants from infection, and the pro-SmAMP2 gene was previously used to protect transgenic tobacco and Arabidopsis plants from phytopathogens. In this study, the pro-SmAMP2 gene under control of viral CaMV35S promoter or under control of its own pro-SmAMP2 promoter was transformed into cultivated potato plants of two cultivars, differing in the resistance to Alternaria: Yubiley Zhukova (resistant) and Skoroplodny (susceptible). With the help of quantitative real-time PCR, it was demonstrated that transgenic potato plants expressed the pro-SmAMP2 gene under control of both promoters at the level comparable to or exceeding the level of the potato actin gene. Assessment of the immune status of the transformants demonstrated that expression of antimicrobial peptide pro-SmAMP2 gene was able to increase the resistance to a complex of Alternaria sp. and Fusarium sp. phytopathogens only in potato plants of the Yubiley Zhukova cultivar. The possible role of the pro-SmAMP2 products in protecting potatoes from Alternaria sp. and Fusarium sp. is discussed.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) Pro12Ala polymorphism and risk for pediatric obesity

NARCIS (Netherlands)

Dedoussis, George V; Vidra, Nikoleta; Butler, Johannah; Papoutsakis, Constantina; Yannakoulia, Mary; Hirschhorn, Joel N; Lyon, Helen N; Vidra, Nikoletta

BACKGROUND: Variation in the peroxisome-proliferator-activated receptor gamma (PPARgamma) gene has been reported to alter the risk for adiposity in adults. METHODS: We investigated the gender related association between the Pro12Ala variant (rs1801282) in obesity and insulin resistance traits in 794

Polymorphisms of the ABCB1 gene in the pakistani population

International Nuclear Information System (INIS)

Farhat, K.; Waheed, A.

2015-01-01

Objective: To investigate the frequency of the single nucleotide polymorphism C1236Tin exon 12 of the ABCB1 gene in Pakistani population and to compare it with published data on Asian and Caucasian populations. Study Design: Across-sectional observational study. Place and Duration of Study: Combined Military Hospital, Rawalpindi and Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, from August 2012 to May 2013. Methodology: C1236T polymorphism was investigated in 426 Pakistani subjects. The frequency was compared with the published data on other Asian and Caucasian populations. Results: The frequencies of ABCB1 C1236T were 16.4% for CC, 44.1% for CT and 39.4% for TT. Pakistanis differed significantly from all the European populations compared in the distribution of the TT genotype of C1236TABCB1 (p < 0.05). The Pakistani population also differed significantly from some of the European populations in the distribution of CC and CT genotype (p < 0.05). Conclusion: There was significant difference in the genotype frequency of the ABCB1 gene compared to other populations. This study has provided a framework for future pharmacogenetic and pharmacokinetic studies on this polymorphic variant of ABCB1 gene in the Pakistani population. (author)

Role of Endothelial Nitric Oxide Synthase Gene Polymorphisms ...

African Journals Online (AJOL)

maintenance of pregnancy, but it is rather controversial whether polymorphisms of the gene encoding for eNOS are associated ... specific human leukocyte antigen alleles that seem to be ... prevents the contractions of the uterine myometrium directly or by an ... an anatomical factor, to avoid this possible bias all candidates.

IRGM gene polymorphisms and risk of gastric cancer.

NARCIS (Netherlands)

Burada, F.; Plantinga, T.S.; Ioana, M.; Rosentul, D.; Angelescu, C.; Joosten, L.A.B.; Netea, M.G.; Saftoiu, A.

2012-01-01

OBJECTIVE: The study aimed to assess the possible association of polymorphisms in the autophagy gene IRGM (rs13361189 and rs4958847) with the risk of gastric cancer. METHODS: A total of 102 patients with gastric adenocarcinoma, 52 with chronic gastritis and 351 healthy controls were included in this

Impact of Maspin Polymorphism rs2289520 G/C and Its Interaction with Gene to Gene, Alcohol Consumption Increase Susceptibility to Oral Cancer Occurrence.

Science.gov (United States)

Yang, Po-Yu; Miao, Nae-Fang; Lin, Chiao-Wen; Chou, Ying-Erh; Yang, Shun-Fa; Huang, Hui-Chuan; Chang, Hsiu-Ju; Tsai, Hsiu-Ting

2016-01-01

The purpose of this study was to identify gene polymorphisms of mammary serine protease inhibitor (Maspin) specific to patients with oral cancer susceptibility and clinicopathological status. Three single-nucleotide polymorphisms (SNPs) of the Maspin gene from 741 patients with oral cancer and 601 non-cancer controls were analyzed by real-time PCR. The participants with G/G homozygotes or with G/C heterozygotes of Maspin rs2289520 polymorphism had a 2.07-fold (p = 0.01) and a 2.01-fold (p = 0.02) risk of developing oral cancer compared to those with C/C homozygotes. Moreover, gene-gene interaction increased the risk of oral cancer susceptibility among subjects expose to oral cancer related risk factors, including areca, alcohol, and tobacco consumption. G allele of Maspin rs2289520 polymorphism may be a factor that increases the susceptibility to oral cancer. The interactions of gene to oral cancer-related environmental risk factors have a synergetic effect that can further enhance oral cancer development.

Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease

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Long Wang

2018-01-01

Full Text Available Objective: To study the correlation between the GP78 gene polymorphism and blood fat, blood glucose, blood pressure and coronary atherosclerotic heart disease. Methods: A total of 72 patients with coronary atherosclerotic heart disease were selected as the observation group, and 68 healthy participants were selected as the control group. The gp78 gene polymorphism of both groups was studied via polymerase chain reaction-restriction fragment length polymorphism (RFLP. At the same time, the multiple expression quantities of the GP78 gene in the tissues of both groups were tested via fluorogenic quantitative PCR, enzyme-linked immunosorbent assay (ELISA and Western-blotting assay. Furthermore, the blood fat, blood glucose and blood pressure of subjects in both groups were tested. Results: The percentages of the gp78 gene polymorphisms of Arg/Arg, Arg/Gly and Gly/Gly at the 145 locus of the study subjects in the observation group were 12.3%, 43.2% and 44.5%, respectively, while those in the control group were 74.3%, 11.2% and 14.5%, respectively, and there were significant differences between both groups. Based on the test results of the blood fat, blood glucose and blood pressure of the objects in the observation group and control group, significant differences were found between the two groups (P<0.05. Conclusion: There was a significant correlation between the 145 locus of the gp89 gene and coronary atherosclerotic heart disease, indexes of blood fat, blood glucose and blood pressure. Keywords: blood fat, blood glucose, blood pressure, coronary sclerosis, heart disease

RERTR progress in Mo-99 production from LEU

Energy Technology Data Exchange (ETDEWEB)

Vandegrift, G.F.; Conner, C.; Aase, S.; Bakel, A.; Bowers, D.; Freiberg, E.; Gelis, A.; Quigley, K.J.; Snelgrove, J.L. [Argonne National Laboratory 9700 S. Cass Avenue, Argonne, IL (United States)

2002-07-01

The ANL RERTR program is performing R and D supporting conversion of {sup 99}Mo production from HEU to LEU targets. Irradiation and processing of LEU targets were demonstrated at the Argentine Ezeiza Atomic Center. Target irradiation and disassembly were flawless, but the processing is not fully developed. In addition to preparing for, assisting in, and analyzing results of the demonstration, we performed other R and D related to LEU conversion: (1) designing a prototype production dissolver for digesting irradiated LEU foils in alkaline solutions and developing means to simplify digestion, (2) modifying ion-exchange columns used in the CNEA recovery and purification of {sup 99}Mo to deal with the lower volumes generated from LEU-foil digestion, (3) measuring the performance of new inorganic sorbents that outperform alumina for recovering Mo(VI) from nitric acid solutions containing high concentrations of uranium nitrate, and (4) developing means to facilitate the concentration and calcination of waste nitric-acid/LEU-nitrate solutions from {sup 99} Mo production. (author)

DNA repair gene polymorphisms in relation to chromosome aberration frequencies in retired radiation workers

International Nuclear Information System (INIS)

Wilding, Craig S.; Relton, Caroline L.; Rees, Gwen S.; Tarone, Robert E.; Whitehouse, Caroline A.; Tawn, E. Janet

2005-01-01

Polymorphic variation in DNA repair genes was examined in a group of retired workers from the British Nuclear Fuels plc facility at Sellafield in relation to previously determined translocation frequencies in peripheral blood lymphocytes. Variation at seven polymorphisms in four genes involved in the base excision repair (XRCC1 R194W, R399Q and a [AC] n microsatellite in the 3' UTR) and double strand break repair (XRCC3 T241M and a [AC] n microsatellite in intron 3 of XRCC3, XRCC4 I134T, and a GACTAn microsatellite located 120kb 5' of XRCC5) pathways was determined for 291 retired radiation workers who had received cumulative occupational external radiation doses of between 0 and 1873mSv. When the interaction between radiation dose and each DNA repair gene polymorphism was examined in relation to translocation frequency there was no evidence for any of the polymorphisms studied influencing the response to occupational exposure. A positive interaction observed between genotype (individuals with at least one allele >=20 repeat units) at a microsatellite locus in the XRCC3 gene and smoking status should be interpreted cautiously because interactions were investigated for seven polymorphisms and two exposures. Nonetheless, further research is warranted to examine whether this DNA repair gene variant might be associated with a sub-optimal repair response to smoking-induced DNA damage and hence an increased frequency of translocations

Retracted Association of STAT4 gene polymorphism with systemic lupus erythematosus / lupus nephritis risk.

Science.gov (United States)

Zhou, Tian-Biao; Jiang, Zong-Pei; Qin, Yuan-Han; Zhou, Jia-Fan

2014-04-16

The association of STAT4 gene polymorphism with systemic lupus erythematosus (SLE) / lupus nephritis (LN) results from the published studies is still conflicting. This meta-analysis was performed to evaluate the relationship between STAT4 rs7574865, rs16833431, rs11889341, rs8179673, rs10168266, rs7582694, rs3821236, rs7601754 gene polymorphism and SLE / LN, and to explore whether STAT4 gene polymorphism could become a predictive marker for SLE / LN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of September 1, 2013, and eligible investigations were synthesized using meta-analysis method. 24 investigations were identified for the analysis of association between STAT4 gene polymorphism and SLE, consisting of 31190 patients with SLE and 43940 controls. In STAT4 rs7574865, there was a marked association between T allele or TT genotype and SLE susceptibility (T: OR=1.53, 95% CI: 1.30-1.79, Prs7574865 gene polymorphism was not associated with the LN risk. Our results indicate that T allele or TT homozygous is a significant risk genetic molecular marker to predict the SLE susceptibility and GG genotype is a valuable marker to against the SLE risk, but the association was not found for LN. However, more investigations are required to further clarify the association of the T allele or TT homozygous with SLE / LN susceptibility. This article is protected by copyright. All rights reserved.

7 CFR 1.198 - Settlement.

Science.gov (United States)

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false Settlement. 1.198 Section 1.198 Agriculture Office of....198 Settlement. The applicant and agency counsel may agree on a proposed settlement of the award before final action on the application, either in connection with a settlement of the underlying...

Effects of bovine prolactin gene polymorphism within exon 4 on milk ...

African Journals Online (AJOL)

STORAGESEVER

2009-10-05

Oct 5, 2009 ... In this study, polymorphism of prolactin gene was analyzed as a candidate gene responsible for ... studied. Based on important role of prolactin gene in milk related traits and their genetic trends in dairy cattle, the aims of this study were, to screen ..... isolation and selection towards high fat and protein per-.

Angiotensin-II type 1 receptor gene polymorphism and diabetic microangiopathy

DEFF Research Database (Denmark)

Tarnow, L; Cambien, Francois; Rossing, P

1996-01-01

with proliferative retinopathy and without diabetic retinopathy was found either: 77 (50%) / 66 (42%) / 13 (8%) vs. 42 (63%) / 22 (33%) / 3 (4%) had AA/AC/CC genotypes, respectively. CONCLUSIONS: The A1166-->C polymorphism in the angiotensin-II type 1 receptor gene does not contribute to the genetic susceptibility...... is present particularly in vascular smooth muscle cells, myocardium and the kidney. A transversion of adenine to cytosine at nucleotide position 1166 in the gene coding for the angiotensin-II type 1 receptor has been associated with hypertension in the non-diabetic population. METHODS: We studied...... the relationship between the A1166-->C polymorphism in the angiotensin-II type 1 receptor gene in patients with insulin dependent diabetes mellitus (IDDM) and diabetic nephropathy (121 men, 77 women, age 41 +/- 10 years, diabetes duration 27 +/- 8 years) and in IDDM patients with normoalbuminuria (116 men, 74...

A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis.

Science.gov (United States)

Peng, Wen-jia; Pan, Hai-feng; Tao, Jin-hui; Wang, Bing-xiang; Lu, Man-man; Wang, Song; He, Qian; Wang, Jing

2012-09-01

We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case-control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) -1722T/C, CTLA-4 -318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36-0.54; TT vs. TG + GG: OR 0.48, 95% CI 0.39-0.59; TT + TG vs. GG: OR 0.74, 95% CI 0.66-0.83; T vs. G: OR 0.72, 95% CI 0.66-0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.

An alternative LEU design for the FRM-II

International Nuclear Information System (INIS)

Hanan, N.A.; Mo, S.C.; Smith, R.S.; Matos, J.E.

1996-01-01

The Alternative LEU Design for the FRM-II proposed by the RERTR Program at Argonne National Laboratory (ANL) has a compact core consisting of a single fuel element that uses LEU silicide fuel with a uranium density of 4.5 g/cm 3 and has a power level of 32 MW. Both the HEU design by the Technical University of Munich (TUM) and the alternative LEU design by ANL have the same fuel lifetime (50 days) and the same neutron flux performance. LEU silicide fuel with 4.5 g/cm 3 has been thoroughly tested and is fully-qualified, licensable, and available now for use in a high flux reactor such as the FRM-II. The following issues raised by TUM were addressed in Ref. 1: qualification of HEU and LEU silicide fuels, gamma heating in the heavy water reflector, radiological consequences of larger fission product and plutonium inventories in the LEU core, and cost and schedule. The conclusions of these analyses are summarized below. This paper addresses three additional safety issues that were raised by TUM in Ref. 2: stability of the involute fuel plates, a hypothetical accident involving the configuration of the reflector, and a loss of primary coolant flow transient due to an interrupted power supply. Based on the excellent results for the Alternative LEU Design that were obtained in these analyses, the RERTR Program concludes that all of the major technical issues regarding use of LEU fuel instead of HEU fuel in the FRM-II have been successfully resolved and that it is definitely feasible to use LEU fuel in the FRM-II without compromising the safety or performance of the facility

Transcobalamin 776C-->G polymorphism is associated with peripheral neuropathy in elderly with high folate intake

Science.gov (United States)

Background: The 776C-->G polymorphism of the vitamin B-12 transport protein transcobalamin gene (TCN2) (rs1801198; Pro259Arg) is associated with a lower holotranscobalamin concentration in plasma. This effect may reduce the availability of vitamin B-12 to tissues even when vitamin B-12 intake is ade...

Lack of association of TNFalpha gene polymorphisms and recurrent pregnancy loss in Caucasian women.

Science.gov (United States)

Pietrowski, Detlef; Bettendorf, Herta; Keck, Christoph; Bürkle, Bernd; Unfried, Gertrud; Riener, Eva-Katrin; Hefler, Lukas A; Tempfer, Clemens

2004-02-01

The tumor necrosis factor alpha (TNFalpha) gene plays an important role in immunology and inflammation. Variant alleles of TNFalpha are associated with altered RNA and serum protein levels in humans. Conflicting results have been obtained regarding the role of TNFalpha during pregnancy and recurrent pregnancy loss (RPL). This study investigated the relationship between RPL and two polymorphisms in the promoter of the TNFalpha gene (TNFalpha -308 and -863). Genotyping was performed in 168 RPL women and 212 ethnically matched healthy individuals. In addition, we performed analysis of TNFalpha serum protein levels. We demonstrate that neither the polymorphism -308 nor the polymorphism -863 of the TNFalpha gene is associated with RPL in Caucasian women. In addition, we did not find any association between TNFalpha serum levels and the occurrence of RPL in a subset of 36 RPL women and 36 healthy individuals. We conclude that TNFalpha polymorphisms and resting blood TNFalpha levels do not correlate with the propensity to recurrent pregnancy loss in Caucasian women.

Interleukin 18 receptor 1 gene polymorphisms are associated with asthma

DEFF Research Database (Denmark)

Zhu, Guohua; Whyte, Moira K B; Vestbo, Jørgen

2008-01-01

The interleukin 18 receptor (IL18R1) gene is a strong candidate gene for asthma. It has been implicated in the pathophysiology of asthma and maps to an asthma susceptibility locus on chromosome 2q12. The possibility of association between polymorphisms in IL18R1 and asthma was examined by genotyp...

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

OpenAIRE

Bao, Ji-Ming; Song, Xian-Lu; Hong, Ying-Qia; Zhu, Hai-Li; Li, Cui; Zhang, Tao; Chen, Wei; Zhao, Shan-Chao; Chen, Qing

2014-01-01

Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence interval...

Are genes associated with energy metabolism important in asthma and BMI?

Science.gov (United States)

Szczepankiewicz, Aleksandra; Breborowicz, Anna; Sobkowiak, Paulina; Popiel, Anna

2009-02-01

Increased serum leptin levels have been observed in asthmatic patients. Leptin, via proliferation and activation of Th2 cells, may induce inflammation in asthma. It has also been demonstrated that leptin mRNA expression and protein levels increase in response to inflammatory stimuli. We hypothesized that polymorphisms in the leptin receptor, leptin and ghrelin genes, may affect their expression and, therefore, be responsible for altered response to increased leptin levels observed in asthma. To our knowledge, there were no studies on a potential role of LEPR, LEP, and GHRL polymorphisms in asthma. We analyzed 129 pediatric patients with asthma and 114 healthy children from the control group ranging from 6 to 18 years of age. The diagnosis of allergic asthma was based on clinical symptoms, the lung function test, and the positive skin prick test and/or increased immunoglobulin E (IgE) levels. Polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analyses were performed with Statistica v.7.1 software (Statistica, StatSoft, Poland; available free at http://www.broad.mit.edu/mpg/haploview/index.php). Linkage disequilibrium analysis was performed with Haploview v.4.0. We observed a statistically significant association of the 3'UTR A/G and the -2549A/G polymorphisms of the leptin gene with asthma. No association with asthma was observed for the K109R and the Q223R polymorphisms of the LEPR gene and the Met72Leu polymorphism of the ghrelin gene. In the analysis of body mass index (BMI) stratified by genotype, we found an association of the -2549A/G LEP, but not of LEPR and GHRL polymorphisms, with higher BMI values in asthmatic patients. We found suggestive evidence for linkage between the two polymorphisms of the LEPR gene (D' = 0.84 CI: 0.71-0.92; r(2) = 0.29) in linkage disequilibrium analysis: The GG haplotype was more frequent in the control healthy group (p = 0.057). No linkage

Ubiquinol decreases monocytic expression and DNA methylation of the pro-inflammatory chemokine ligand 2 gene in humans

Directory of Open Access Journals (Sweden)

Fischer Alexandra

2012-10-01

Full Text Available Abstract Background Coenzyme Q10 is an essential cofactor in the respiratory chain and serves in its reduced form, ubiquinol, as a potent antioxidant. Studies in vitro and in vivo provide evidence that ubiquinol reduces inflammatory processes via gene expression. Here we investigate the putative link between expression and DNA methylation of ubiquinol sensitive genes in monocytes obtained from human volunteers supplemented with 150 mg/ day ubiquinol for 14 days. Findings Ubiquinol decreases the expression of the pro-inflammatory chemokine (C-X-C motif ligand 2 gene (CXCL2 more than 10-fold. Bisulfite-/ MALDI-TOF-based analysis of regulatory regions of the CXCL2 gene identified six adjacent CpG islands which showed a 3.4-fold decrease of methylation status after ubiquinol supplementation. This effect seems to be rather gene specific, because ubiquinol reduced the expression of two other pro-inflammatory genes (PMAIP1, MMD without changing the methylation pattern of the respective gene. Conclusion In conclusion, ubiquinol decreases monocytic expression and DNA methylation of the pro-inflammatory CXCL2 gene in humans. Current Controlled Trials ISRCTN26780329.

N-acetyltransferase 2 gene polymorphism and presbycusis.

Science.gov (United States)

Unal, Murat; Tamer, Lülüfer; Doğruer, Zeynep Nil; Yildirim, Hatice; Vayisoğlu, Yusuf; Camdeviren, Handan

2005-12-01

The enzyme of N-acetyltransferase (NAT) is involved in the metabolism and detoxification of cytotoxic and carcinogenic compounds as well as reactive oxygen species (ROS). The excessive amount of ROS generation occurs in the ageing inner ear. The exact etiopathogenesis of presbycusis is not known, but it is generally accepted that it is the result of series of insults, such as physiologic age-related degeneration, noise exposure, medical disorders and their treatment, as well as hereditary susceptibility. The effect of aging shows a wide interindividual range; we aimed to investigate whether profiles of NAT2 genotypes may be associated with the risk of presbycusis. Hospital-based, case-control study. We examined 68 adults with presbycusis and 98 healthy controls. DNA was extracted from whole blood, and the polymorphisms of NAT2*5A, NAT2*6A, NAT2*7A/B, and NAT2*14A were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of presbycusis were examined by use of logistic regression analyses to calculate odds ratios and 95% confidence intervals. Gene polymorphisms at NAT2*5A, NAT2*7A/B, and NAT2*14A in subjects with presbycusis were not significantly different from in the controls (P > .05). However, in NAT2*6A, the risk of presbycusis was 15.2-fold more in individuals with mutant allele than subjects with wild genotype (P = .013). Individuals with NAT2*6A heterozygote allele had a 0.34-fold less risk in the development of presbycusis than subjects with mutant allele (P = .032) We demonstrated a significant association between the NAT2*6A polymorphism and age-related hearing loss in this population. However, the sample size was relatively small, and further studies need to investigate the exact role of NAT2 gene polymorphism in the etiopathogenesis of the presbycusis.

Association Between Genetic Polymorphisms in the XRCC1, XRCC3, XPD, GSTM1, GSTT1, MSH2, MLH1, MSH3, and MGMT Genes and Radiosensitivity in Breast Cancer Patients

International Nuclear Information System (INIS)

Mangoni, Monica; Bisanzi, Simonetta; Carozzi, Francesca; Sani, Cristina; Biti, Giampaolo; Livi, Lorenzo; Barletta, Emanuela; Costantini, Adele Seniori; Gorini, Giuseppe

2011-01-01

Purpose: Clinical radiosensitivity varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH2 (gIVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Methods and Materials: Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Results: Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH2 gIVS12-6nt-C allele (HR = 53.36; 95% confidence intervals [95% CI], 3.56-798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity (HR = 38.26; 95% CI, 1.19-1232.52). Conclusions: To our knowledge, this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be

Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review

International Nuclear Information System (INIS)

Balasubramanian, SP; Azmy, IAF; Higham, SE; Wilson, AG; Cross, SS; Cox, A; Brown, NJ; Reed, MW

2006-01-01

Interleukins and cytokines play an important role in the pathogenesis of many solid cancers. Several single nucleotide polymorphisms (SNPs) identified in cytokine genes are thought to influence the expression or function of these proteins and many have been evaluated for their role in inflammatory disease and cancer predisposition. The aim of this study was to evaluate any role of specific SNPs in the interleukin genes IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 in predisposition to breast cancer susceptibility and severity. Candidate single nucleotide polymorphisms (SNPs) in key cytokine genes were genotyped in breast cancer patients and in appropriate healthy volunteers who were similar in age, race and sex. Genotyping was performed using a high throughput allelic discrimination method. Data on clinico-pathological details and survival were collected. A systematic review of Medline English literature was done to retrieve previous studies of these polymorphisms in breast cancer. None of the polymorphisms studied showed any overall predisposition to breast cancer susceptibility, severity or to time to death or occurrence of distant metastases. The results of the systematic review are summarised. Polymorphisms within key interleukin genes (IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 do not appear to play a significant overall role in breast cancer susceptibility or severity

Allelic polymorphism of Makoei sheep leptin gene identified by ...

African Journals Online (AJOL)

use

2011-12-05

Dec 5, 2011 ... Lord et al., 1998) have shed light on the influence of leptin on both the .... A weak correlation between leptin serum levels and cow body condition ... Detection of polymorphisms in the ovine leptin (LEP) gene: .... Signals that.

HC-Pro silencing suppressor significantly alters the gene expression profile in tobacco leaves and flowers

Directory of Open Access Journals (Sweden)

Lehto Kirsi

2011-04-01

Full Text Available Abstract Background RNA silencing is used in plants as a major defence mechanism against invasive nucleic acids, such as viruses. Accordingly, plant viruses have evolved to produce counter defensive RNA-silencing suppressors (RSSs. These factors interfere in various ways with the RNA silencing machinery in cells, and thereby disturb the microRNA (miRNA mediated endogene regulation and induce developmental and morphological changes in plants. In this study we have explored these effects using previously characterized transgenic tobacco plants which constitutively express (under CaMV 35S promoter the helper component-proteinase (HC-Pro derived from a potyviral genome. The transcript levels of leaves and flowers of these plants were analysed using microarray techniques (Tobacco 4 × 44 k, Agilent. Results Over expression of HC-Pro RSS induced clear phenotypic changes both in growth rate and in leaf and flower morphology of the tobacco plants. The expression of 748 and 332 genes was significantly changed in the leaves and flowers, respectively, in the HC-Pro expressing transgenic plants. Interestingly, these transcriptome alterations in the HC-Pro expressing tobacco plants were similar as those previously detected in plants infected with ssRNA-viruses. Particularly, many defense-related and hormone-responsive genes (e.g. ethylene responsive transcription factor 1, ERF1 were differentially regulated in these plants. Also the expression of several stress-related genes, and genes related to cell wall modifications, protein processing, transcriptional regulation and photosynthesis were strongly altered. Moreover, genes regulating circadian cycle and flowering time were significantly altered, which may have induced a late flowering phenotype in HC-Pro expressing plants. The results also suggest that photosynthetic oxygen evolution, sugar metabolism and energy levels were significantly changed in these transgenic plants. Transcript levels of S

10 CFR 205.198 - Discovery.

Science.gov (United States)

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Discovery. 205.198 Section 205.198 Energy DEPARTMENT OF... of Proposed Disallowance, and Order of Disallowance § 205.198 Discovery. (a) If a person intends to file a Motion for Discovery, he must file it at the same time that he files his Statement of Objections...

Association between CD14 gene polymorphisms and cancer risk: a meta-analysis.

Directory of Open Access Journals (Sweden)

Jun Wang

Full Text Available BACKGROUND: Two polymorphisms, -260C/T and -651C/T, in the CD14 gene have been implicated in susceptibility to cancer. However, the results remain inconclusive. This meta-analysis aimed to investigate the association between the two polymorphisms and risk of cancer. METHODS: All eligible case-control studies published up to March 2014 were identified by searching PubMed, Web of Science, CNKI and WanFang database. Pooled odds ratio (OR with 95% confidence interval (CI were used to access the strength of this association in fixed- or random-effects model. RESULTS: 17 case-control studies from fourteen articles were included. Of those, there were 17 studies (4198 cases and 4194 controls for -260C/T polymorphism and three studies (832 cases and 1190 controls for -651C/T polymorphism. Overall, no significant associations between the two polymorphisms of CD14 gene and cancer risk were found. When stratified by ethnicity, cancer type and source of control, similar results were observed among them. In addition, in further subgroups analysis by Helicobacter pylori (H. pylori infection status and tumor location in gastric cancer subgroup, we found that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. CONCLUSIONS: This meta-analysis suggests that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. However, large and well-designed studies are warranted to validate our findings.

Role of ACE and PAI-1 Polymorphisms in the Development and Progression of Diabetic Retinopathy

Science.gov (United States)

Saleem, Saba; Azam, Aisha; Maqsood, Sundus Ijaz; Muslim, Irfan; Bashir, Shaheena; Fazal, Nosheen; Riaz, Moeen; Ali, Syeda Hafiza Benish; Niazi, Muhammad Khizar; Ishaq, Mazhar; Waheed, Nadia Khalida; Qamar, Raheel; Azam, Maleeha

2015-01-01

In the present study we determined the association of angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms with diabetic retinopathy (DR) and its sub-clinical classes in Pakistani type 2 diabetic patients. A total of 353 diabetic subjects including 160 DR and 193 diabetic non retinopathy (DNR) as well as 198 healthy controls were genotyped by allele specific polymerase chain reaction (PCR) for ACE Insertion/Deletion (ID) polymorphism, rs4646994 in intron 16 and PAI-1 4G/5G (deletion/insertion) polymorphism, rs1799768 in promoter region of the gene. To statistically assess the genotype-phenotype association, multivariate logistic regression analysis was applied to the genotype data of DR, DNR and control individuals as well as the subtypes of DR. The ACE genotype ID was found to be significantly associated with DR (p = 0.009, odds ratio (OR) 1.870 [95% confidence interval (CI) = 1.04–3.36]) and its sub-clinical class non-proliferative DR (NPDR) (p = 0.006, OR 2.250 [95% CI = 1.098–4.620]), while PAI polymorphism did not show any association with DR in the current cohort. In conclusion in Pakistani population the ACE ID polymorphism was observed to be significantly associated with DR and NPDR, but not with the severe form of the disease i.e. proliferative DR (PDR). PMID:26658948