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Sample records for il4 gene polymorphism

  1. Association between interleukin-4 (IL-4), gene polymorphisms (C ...

    African Journals Online (AJOL)

    Nourollah Ramroodi

    2016-06-10

    Jun 10, 2016 ... The study was approved by the ethics in medical research com- mittee at Zahedan .... 220 bp. IL-4 gene important polymorphisms in Iranian migraineurs. 31 ..... DA, et al. Genetic and environmental influences on migraine: a.

  2. Polymorphisms of IL-4, IL-4Rα, and AICDA Genes in Adult Allergic Asthma

    Institute of Scientific and Technical Information of China (English)

    崔天盆; 王琳; 吴健民; 胡丽华; 谢俊刚

    2003-01-01

    Summary: The relationship between 3 polymorphisms sites [interleulin-4 (IL-4), IL-4 receptor (IL-4R) α chain and activation-induced cytidine deaminase (AICDA)] and adult allergic asthma in Chinawas studied. By using case-control method, DNA and clinical data were obtained from allergic asth-matic patients and compared with those in the control subjects. The subjects were genotyped for theIL-4 C-589T promoter polymorphism, the IL-4R α chain Q576R and the AICDA C8408T by poly-merase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The resultsshowed that the IL-4 C-589T was not associated with adult allergic asthma in China. However, theIL-4R α chain 576R/R and AICDA 8408T/T frequency was significantly increased in allergic asthmagroup as compared with that in the control group [odd ratio (OR)= 3. 797 and 9. 127, respectively;P<0.01)] and was correlated with the increased plasma total IgE. These data suggested that theIL-4R α chain 576R/R and AICDA 8408T/T genotypes confer genetic susceptibility to adult allergicasthma in China.

  3. A preliminary study on the association of single nucleotide polymorphisms of interleukin 4 (IL4, IL13, IL4 receptor alpha (IL4Rα & Toll-like receptor 4 (TLR4 genes with asthma in Indian adults

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    Parisa Davoodi

    2015-01-01

    Full Text Available Background & objectives: Interleukin 4 (IL4 and IL13 genes are believed to be responsible for inflammation of the airways in asthmatics. These share a common receptor component called IL4Rα which is another potentially important candidate gene linked to asthma phenotypes. Another gene Toll-like receptor 4 (TLR4 might affect the incidence or progression of asthma through the expression of proinflammatory genes. Several single nucleotide polymorphisms (SNPs in IL4, IL13, IL4Rα and TLR4 have been reported to be linked to asthma or related phenotypes in several ethnic populations using linkage studies and association studies. However, the results have not been consistent. We investigated five SNPs (C-589T and C-33T of IL4, G+2044A of IL13, A+1902G of IL4Rα, and A+896G of TLR4 in patients with adult onset asthma to evaluate their role in manifestation and severity of asthma. Methods: Adult (>18 yr of age patients with asthma (n=100 and healthy controls (n=50 were included in the study. Genotyping was performed using sequenom MassARRAY technology. Results: The mutant alleles of the C-589T and C-33T SNPs in the promoter region of IL4 were present in 4 per cent patients with asthma but absent from the control group suggesting that the variations in IL4 may contribute to asthma occurrence. The SNPs of other genes were seen in both controls and patients. Interpretation & conclusions: The results suggest the possible association between the genetic distribution of C-589T and C-33T SNPs of IL4 with asthma in Indian adults.

  4. The Effect of IL-4 Gene Polymorphisms on Cytokine Production in Patients with Chronic Periodontitis and in Healthy Controls

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    Jirina Bartova

    2014-01-01

    Full Text Available Chronic periodontitis (CP is an inflammatory disease of the teeth-supporting tissues in which genetic predisposition, dental plaque bacteria, and immune mechanisms all play important roles. The aim of this study was to evaluate the occurrence of IL-4 gene polymorphisms in chronic periodontitis and to investigate the association between polymorphisms and cytokines production after bacterial stimulation. Sixty-two subjects (47 CP patients and 15 healthy controls with detected two polymorphisms in the IL-4 gene (-590C/T and intron 3 VNTR were examined. Production of cytokines (IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-17, TNFα, INFγ, and VEGF was studied after in vitro stimulation of isolated peripheral blood by mitogens (Pokeweed mitogen, Concanavalin A, dental plaque bacteria (Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, and Prevotella intermedia, and Heat Shock Protein (HSP 70 by the Luminex multiplex cytokine analysis system. The results were correlated with IL-4 genotypes in patients with CP and healthy controls. The mononuclear cells isolated from peripheral blood of CP patients with selected IL-4 polymorphisms significantly altered the production of IFNγ, IL-10, IL-1β, IL-1α, TNFα, and IL-6 after stimulation by HSP 70 or selected bacteria (from P<0.001 to P<0.05. IL-4 gene polymorphisms may influence the function of mononuclear cells to produce not only interleukin-4 but also other cytokines, especially in patients with CP.

  5. Associação dos polimorfismos dos genes TGF-beta1, CD14, IL-4, IL-4R e ADAM33 com a gravidade da asma em crianças e adolescentes Association of TGF-beta1, CD14, IL-4, IL-4R and ADAM33 gene polymorphisms with asthma severity in children and adolescents

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    Isabel C. J. de Faria

    2008-06-01

    Full Text Available OBJETIVO: Verificar, em uma amostra de pacientes com asma atópica persistente leve, moderada e grave, a associação entre os polimorfismos dos genes fator de crescimento transformante-beta1 (TGF-beta1 (C-509T e T869C, CD14 (C-159T, IL-4 (C-590T, IL-4R (ILe50Val e ADAM33 (S_2 com a gravidade da asma. MÉTODOS: Realizou-se um estudo clínico laboratorial prospectivo em pacientes com asma atópica persistente, comparados a um grupo controle no Hospital Universitário da Universidade Estadual de Campinas nos anos de 2006 e 2007. A análise do polimorfismo T869C do gene TGF-beta1 foi realizada pela técnica de reação em cadeia da polimerase (PCR + sistema de amplificação refratária de mutação (ARMS. Os outros polimorfismos, C-509T do gene TGF-beta1, C-159T do gene CD14, C-590T da IL-4, ILe50Val da IL-4Ra e S2 do gene ADAM33, foram detectados por PCR e enzima de restrição. RESULTADOS: Foram incluídos 88 pacientes com asma atópica persistente (27 leves, 23 moderados e 38 graves e 202 indivíduos saudáveis, doadores de sangue. Em relação ao polimorfismo T869C (TGF-beta1, observou-se uma associação entre o genótipo CC e os pacientes com asma grave. Nenhuma associação foi encontrada com os polimorfismos C-509T (TGF-beta1, C-590T (IL4 e S_2 (ADAM33. Quando se comparou a distribuição da freqüência genotípica do polimorfismo C-159T (CD14 na asma grave com o grupo controle, foi observado um resultado significativo com o genótipo TT. Houve associação significativa do genótipo Val/Val (IL-4R com a asma leve. CONCLUSÃO: Nossos resultados indicam que os polimorfismos T869C (TGF-beta1, C-159T (CD14 e Val/Val (IL-4R podem estar envolvidos na modulação da gravidade da asma.OBJECTIVE: To verify the association of transforming growth factor-beta1 (TGF-beta1 (C-509T and T869C, CD14 (C-159T, IL-4 (C-590T, IL-4R (ILe50Val and ADAM33 (S_2 gene polymorphisms with asthma severity in a sample of patients with mild, moderate and severe

  6. Association between IL-4 and IL-4R Polymorphisms and Periodontitis: A Meta-Analysis

    Science.gov (United States)

    Chen, Xue-Hong

    2017-01-01

    Background. Previous studies have revealed that gene polymorphisms of inflammatory factors may influence the development or progression of periodontitis, a main cause of tooth loss in adults; however, due to limitations of individual studies, inconsistent findings were reported. Objective. To meta-analytically investigate the relationship between periodontitis and the Interleukin-4 (IL-4) and Interleukin-4 receptor (IL-4R) gene polymorphisms. Methods. Databases were searched for relevant case-control studies. After study selection based on the predefined selection criteria, methodological quality assessment and data extraction were conducted independently by two reviewers, before subsequent statistical analyses. Results. 37 studies involving 4,385 patients and 5,168 controls were included. All the studied IL-4 polymorphisms were not significantly associated with periodontitis, except the -33C/T (CT versus CC: OR = 0.50, 95% CI = 0.28–0.88) associated with reduced AgP susceptibility. Positive association was found between IL-4R Q551 polymorphism and periodontitis susceptibility in three genetic models (R versus Q: OR = 1.59, 95% CI = 1.14–2.22; QR versus QQ: OR = 1.84, 95% CI = 1.21–2.80; RR + QR versus QQ: OR = 1.82, 95% CI = 1.22–2.72). Conclusions. A positive association exists between the IL-4R Q551R polymorphism and occurrence of CP. The IL-4 -33 CT genotype is negatively associated with the occurrence of AgP.

  7. ASSOCIATION OF IL-1β, IL-4 AND IL-6 GENES POLYMORPHISMS WITH GENETIC PREDISPOSITION FOR AUTOIMMUNE THYROIDITIS

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    E. M. Biktagirova

    2011-01-01

    Full Text Available Abstract.  Autoimmune  thyroiditis  (Hashimoto’s  thyroiditis,  HT  still  represents  an  unresolved  problem of modern endocrinology, since its etiology and pathogenesis are yet unclear. Cytokines play an important role in the regulation of immune and inflammatory response, therefore, some gene variants encoding them, are considered as potential risk risk factors for autoimmune thyroid diseases. We have genotyped 298 women from the Republic of Tatarstan (RT, control group, 137 persons; HT patients, 161 for the following gene polymorphisms: interleukin-1 beta (IL-1β +3953 C/T (rs 1143634; interleukin 4 (IL-4 -590C/T (rs 2243250, and interleukin 6 (IL-6 -174C/G (rs 1800795, using allele-specific PCR. The results showed a significantly increased frequencies of C allele (P  = 0.0003 and CT genotype (P  = 0.048, OR  = 6.05, 95%CI 2.59-2.97 of  +3953  C/T  of  IL-1β  in  patients  with  Hashimoto's thyroiditis, as compared with control group. The latter  group showed higher prevalence of T allele (P  = 0.0003 and TT genotype (P  = 4.95 Ч 6.10; OR  = 0.15, 95%CI 0.06-0.38. The 590C/T and -174C/G polymorphic variants in, resp., IL-4 and IL-6 genes are not associated with increased risk of this disease among women from RT. (Med. Immunol., 2011, vol. 13, N 6, pp 603-608 

  8. Association of polymorphisms in the human IL4 and IL5 genes with atopic bronchial asthma and severity of the disease.

    Science.gov (United States)

    Freidin, Maxim B; Kobyakova, Olga S; Ogorodova, Ludmila M; Puzyrev, Valery P

    2003-01-01

    Two polymorphisms in the IL4 (G/C 3'-UTR) and IL5 (C-703T) genes were studied in a sample of families whose probands had atopic bronchial asthma (BA) (66 families, n = 183) and in a group of non-cognate individuals with the severe form of the disease (n = 34). The samples were collected from the Russian population in the city of Tomsk (Russia). Using the transmission/disequilibrium test (TDT), a significant association of allele C-703 IL5 with BA was established (TDT = 4.923, p = 0.007 +/- 0.0007). The analysis of 40 individuals with mild asthma and 49 patients with the severe form of the disease revealed a negative association of genotype GG IL4 (OR = 0.39, 95% CI = 0.15-0.99, p = 0.035), and also a trend towards a positive association of the GC IL4 genotype (OR = 2.52, 95% CI = 0.98-6.57, p = 0.052) with mild BA. There was a concordance of the clinical classification of BA severity with the 'genotype' (McNemar's chi(2) test with continuity correction constituted 0.03, d.f. = 1, p = 0.859). These results suggest that polymorphisms in the IL4 and IL5 genes contribute to the susceptibility to atopic BA and could determine the clinical course of the disease.

  9. IL4 gene polymorphism and previous malaria experiences manipulate anti-Plasmodium falciparum antibody isotype profiles in complicated and uncomplicated malaria

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    Kalambaheti Thareerat

    2009-12-01

    Full Text Available Abstract Background The IL4-590 gene polymorphism has been shown to be associated with elevated levels of anti-Plasmodium falciparum IgG antibodies and parasite intensity in the malaria protected Fulani of West Africa. This study aimed to investigate the possible impact of IL4-590C/T polymorphism on anti-P. falciparum IgG subclasses and IgE antibodies levels and the alteration of malaria severity in complicated and uncomplicated malaria patients with or without previous malaria experiences. Methods Anti-P.falciparum IgG subclasses and IgE antibodies in plasma of complicated and uncomplicated malaria patients with or without previous malaria experiences were analysed using ELISA. IL4-590 polymorphisms were genotyped using RFLP-PCR. Statistical analyses of the IgG subclass levels were done by Oneway ANOVA. Genotype differences were tested by Chi-squared test. Results The IL4-590T allele was significantly associated with anti-P. falciparum IgG3 antibody levels in patients with complicated (P = 0.031, but not with uncomplicated malaria (P = 0.622. Complicated malaria patients with previous malaria experiences carrying IL4-590TT genotype had significantly lower levels of anti-P. falciparum IgG3 (P = 0.0156, while uncomplicated malaria patients with previous malaria experiences carrying the same genotype had significantly higher levels (P = 0.0206 compared to their IL4-590 counterparts. The different anti-P. falciparum IgG1 and IgG3 levels among IL4 genotypes were observed. Complicated malaria patients with previous malaria experiences tended to have lower IgG3 levels in individuals carrying TT when compared to CT genotypes (P = 0.075. In contrast, complicated malaria patients without previous malaria experiences carrying CC genotype had significantly higher anti-P. falciparum IgG1 than those carrying either CT or TT genotypes (P = 0.004, P = 0.002, respectively. Conclusion The results suggest that IL4-590C or T alleles participated differently in the

  10. IL-4 alpha chain receptor (IL-4polymorphisms in allergic bronchopulmonary sspergillosis

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    Consolino Judy D

    2006-02-01

    Full Text Available Abstract Background Allergic bronchopulmonary aspergillosis occurs in 7–10% of cystic fibrosis (CF and 1–2% of asthmatic patients. HLA-DR restriction and increased sensitivity to IL-4 stimulation have been proposed as risk factors in these populations. Objective We examined for the presence of IL-4 receptor alpha chain (IL-4Rα single nucleotide polymorphisms (SNPs in ABPA and whether these accounted for increased sensitivity to IL-4 stimulation. Methods One extracellular (ile75val and four cytoplasmic IL-4Rα SNPs were analyzed in 40 CF and 22 asthmatic patients and in 56 non-ABPA CF and asthmatic patients. Sensitivity to IL-4 stimulation was measured by induction of CD23 expression on B cells. Results IL-4Rα SNPs were observed in 95% of ABPA patients. The predominant IL-4Rα SNP was the extracellular IL-4Rα SNP, ile75val, observed in 80% of ABPA patients. Conclusion The presence of IL-4Rα SNPs, principally ile75val, appears to be a genetic risk for the development of ABPA.

  11. Immunological parameters and gene polymorphisms (C-590T IL4, C-597A IL10 in severe bronchial asthma in children from the Krasnoyarsk region, West Siberia

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    Marina V. Smolnikova

    2013-08-01

    Full Text Available Background. Bronchial asthma is a common disease caused by interplay between multiple determinants, including genetic and immune variations. Objective. To investigate the main indices of humoral and cellular branches of immunity, features of cytokine regulation and cytokine genes in children with atopic bronchial asthma (BA with different levels of disease control. Design. Fifty children with controlled BA (CBA and 50 with uncontrolled BA (UBA were analyzed. Mean age in the sample was 13.36±2.24 years. A control group of healthy children (n=50 was also studied. All individuals were Russians (Eastern Slavs from the Krasnoyarsk Territory, West Siberia. Diagnoses, severity and level of disease control were defined according to the Global Initiative for Asthma (GINA recommendations. The lymphocytes were counted in blood using fluorescent microscopy. Humoral branch indices and cytokine levels (IL-2, IL-4, IL-10 and TNF-α in blood serum were measured by ELISA. Genotyping of single-nucleotide polymorphism (SNP in −590 position of the IL4 and −597 position of the IL10 gene was performed by restriction fragment length analysis. Results. No statistically significant differences in total IgE and cytokines blood levels were found in CBA and UBA. However, significant differences between the groups were found for CD3+, CD4+, and CD8+, cell counts. The T-590 allele of the IL4 gene, which is responsible for an increased serum level of IL-4, showed a tendency to an association with UBA. A decreased level of IL-10 enhances control over BA, which proves its association with the allelic variant A-597 IL10. Conclusions. Our data show that children with UBA have higher counts of CD3+, cells and an increase of sub-population of CD4+, -cells as well as higher levels of IgE, IL-4 and TNF-α in blood serum as compared to CBA. Polymorphisms of the IL4 and IL10 genes are associated with allergic inflammation in UBA.

  12. Study of polymorphisms in the interleukin-4 and IL-4 receptor genes in a population of Brazilian patients with multiple sclerosis Estudo de polimorfismos nos genes da interleucina-4 (*33C-T e receptor IL-4 (*Q551R numa população de pacientes brasileiros com esclerose múltipla

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    Thereza Quirico-Santos

    2007-03-01

    Full Text Available This study aimed to investigate in a population of Brazilian patients with multiple sclerosis (MS single-nucleotide polymorphisms (SNP in the promoter region of IL4 (*33C-T and receptor IL4R (*Q551R A-G genes proposed to interfere with disease progression. No significant differences were observed in either of the SNPs investigated between healthy controls (n=135 and MS patients (n=129. However, the IL4+33 TT genotype was significantly (p=0.039 higher in African descendants MS (AF-MS= 9.09% than in Caucasian MS (CA-MS= 1.35%. It was also observed a significant (p=0.016 increase for the IL4R* Q551R CC genotype in AF-MS compared to those of Caucasian ethnicity (AF-MS= 21.62%; CA-MS= 4.35%. These results suggest that IL4+33 and IL4R*Q551 polymorphisms may have a disease-promoting role of TH2 mediators in African MS descendants. Additionally neither IL4 nor IL4R genes are susceptibility factors for Brazilian MS but may be able to modify ethnicity-dependent disease risk and penetrance of susceptibility factors.Este é um estudo inédito realizado numa população brasileira de pacientes portadores de esclerose múltipla (EM visando determinar uma possível associação na expressão de polimorfismo (SNP nos genes da citocina reguladora IL4 (*33C-T e do seu respectivo receptor IL4R (*Q551R A-G capazes de modificar a evolução da doença. Não foi observada diferença significativa em ambos SNPs analisados entre o grupo controle de indivíduos saudáveis (n=135 e os pacientes com EM (n=129. Contudo, o genotipo IL4+33 TT apresentava percentual mais elevado (9,09% nos pacientes EM com descendência africana (AF-EM do que nos descendentes caucasianos (CA-EM=1,35% sendo esta diferença significativa (p=0,039. Também foi observado um aumento significativo (p=0,016 para o genotipo IL4R* Q551R CC nos pacientes AF-EM (21,62% comparando-se com CA-EM (4,35%. Estes resultados indicam que polimorfismos nos genes da citocina IL4 (*33C-T e respectivo receptor IL4R

  13. Relationship of TGF-β and IL-4R gene polymorphisms with risk of classical Hodgkin lymphoma

    Institute of Scientific and Technical Information of China (English)

    王欣如

    2013-01-01

    Objective This study was aimed to analyze the relationship between single nucleotide polymorphisms of transforming growth factor-β1 G-800A and C-509T,interleukin-4 receptor V75I and susceptibility of CHL in adults. Methods Polymerase chain reaction-restriction

  14. Assessment of genetic associations between common single nucleotide polymorphisms in RIG-I-like receptor and IL-4 signaling genes and severe respiratory syncytial virus infection in children: a candidate gene case-control study.

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    Nico Marr

    Full Text Available The majority of cases of severe pediatric respiratory syncytial virus (RSV infection occur in otherwise healthy infants who have no identifiable risk factors, suggesting that additional subclinical factors, such as population genetic variation, influence the course of RSV infection. The objective of this study was to test if common single nucleotide polymorphisms (SNPs in genes encoding for immune signalling components of the RIG-I-like receptor (RLR and IL-4-signalling pathways affect the outcome of RSV infection in early life. We genotyped 8 SNPs using allele-specific probes combined with real-time PCR. Each of the SNPs tested had previously been established to have a functional impact on immune responsiveness and two of the SNPs in the IL4 and IL4R genes had previously been associated with severe RSV bronchiolitis. Association with susceptibility to severe RSV infection was tested by statistically comparing genotype and allele frequencies in infants and young children hospitalized with severe RSV bronchiolitis (n = 140 with two control groups-children who tested positive for RSV but did not require hospitalization (n = 100, and a general population control group (n = 285. Our study was designed with sufficient power (>80% to detect clinically-relevant associations with effect sizes ≥1.5. However, we detected no statistically significant differences in allele and genotype frequencies of the investigated SNPs between the inpatient and control groups. To conclude, we could not replicate the previously reported association with SNPs in the IL4 and IL4R genes in our independent cohort, nor did we find that common SNPs in genes encoding for RLRs and the downstream adapter MAVS were associated with susceptibility to severe RSV infections. Despite the existing evidence demonstrating a functional immunological impact of these SNPs, our data suggest that the biological effect of each individual SNP is unlikely to affect clinical outcomes

  15. single nucleotide Polymorphisms rs2227284, rs2243283 and rs2243288 in the Il-4 Gene show no association with susceptibility to Chronic Hepatitis B in a Chinese Han Population

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of the interleukin-4 (IL-4) gene and outcome of hepatitis B virus (HBV) infection in a Chinese Han population. Methods Total of 501 patients with chronic hepatitis B virus (HBV) infection and 301 controls with self-limiting HBV infection were studied. Three tag SNPs in the IL-4 gene (rs2227284G/T, rs2243283C/G and rs2243288A/G) were genotyped by the Multiplex snapshot technique. The genotype and allele frequencies were calculated and analyzed. Results The three SNPs showed no significant genotype/allele associations with chronic HBV infection. Overall allele P values were:rs2227284, P=0.655, odds ratio (OR) [95%conifdence interval (CI)]=1.070 (0.793-1.445);rs2243283, P=0.849, OR (95%CI)=0.976 (0.758-1.257);rs2243288, P=0.659, OR (95%CI) = 1.060 (0.818-1.375). Overall genotype P values were: rs2227284, P = 0.771; rs2243283, P = 0.571;rs2243288, P=0.902. There were no statistically signiifcant differences between patients with chronic HBV infection and controls. Haplotypes generated by these three SNPs also had no signiifcant differences between the two groups. Conclusions The three tag SNPs of IL-4 were not associated with the outcome of HBV infection in the Han Chinese population.

  16. MOLECULAR BIOLOGY ANALYSIS OF IL -1Β, IL -4, AND IL -1Β RA GENE POLYMORPHISMS IN ETHNIC BASHKIR PATIENTS WITH RHEUMATOID ARTHRITIS, LIVING IN C HELYABINSK REGION

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    A. L. Burmistrova

    2007-01-01

    Full Text Available Abstract. Common polymorphisms of interleukin-1β, receptor antagonist interleukin-1, and interleukin-4 genes have been studied among the patients with rheumatoid arthritis of Bashkir origin, living in Chelyabinsk Region. As a result of study, an increased frequency of interleukin-1β homozygosity for a high-producer allele was found. An association has been revealed between the homozygosity for 2-repeat allele of interleukin-4, and the age of disease onset.

  17. PROGNOSIS FOR PREDISPOSAL TO DEVELOPMENT OF VIRAL HEPATITIS C BASED ON G-308A TNFА, T-330G IL-2, С-590Т IL-4, С-703Т IL-5, AND C-592A IL-10 GENE POLYMORPHISMS

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    V. V. Avdoshina

    2006-01-01

    Full Text Available Abstract. The main objective of this work was to identify allelic variants of cytokine genes at the polymorphic positions of G-308A TNFА, T-330G IL-2, С-590Т IL-4, С-703Т IL-5, and C-592A IL-10, and to assess their contribution to predisposition and resistance of human patients to progression of viral hepatitis C infection. We observed significant increase in frequency of T/G T-330G IL-2 genotype in HCV-infected patients, as compared to healthy individuals. Distribution analysis of C-590T promoter alleles of the IL-4 gene displayed a wide overrepresentation of C/T genotype among HCV-infected patients. Likewise, we have shown the G/A genotype of G-308A TNFA to be highly frequent in the group of HCV-infected patients, whereas this genotype was rare in the sample of healthy persons. When analysing allelic frequencies of cytokine genes at these polymorphic positions, we get an opportunity to predict predisposal for the chronic variant of viral hepatitis C in HCV-infected persons.

  18. Association between IL-4, IL-6 or IL-13 gene polymorphism and chronic periodontitis%IL-4、IL-6和IL-13基因多态性与慢性牙周炎的相关性研究

    Institute of Scientific and Technical Information of China (English)

    胡杉林; 秦飞; 郑江海; 代梅

    2016-01-01

    目的:研究白细胞介素-4(-34C/T和-590C/T)、6(-174G/C和-572C/G)、13(-1112C/T和+1923C/T)的基因多态性与慢性牙周炎的相关性。方法收集2013年10月至2015年10月我院口腔科收治的慢性牙周炎患者120例为CP组,另选取健康受试者120名作为对照组,选用聚合酶链反应-限制性内切酶片段长度多态性分析比较两组的基因型和等位基因分布特点。结果两组受检者IL-4-34位点、IL-4-590位点、IL-6-572位点、IL-13+1923位点的基因型和等位基因频率分布比较差异均无统计学意义(P>0.05);而IL-6-572位点、IL-13-1112位点的基因型和等位基因频率分布比较差异均有统计学意义(P0.05). But there were significant difference in the alleles and genotypes of IL-6-572 and IL-13-1112 locus between the two groups. Conclusion IL-4-34/-590, IL-6-572 and IL-13+1923 gene polymorphisms have nothing to do with chronic periodontitis, while IL-6-572 and IL-13-1112 are related to the occurrence and development of chronic periodontitis.

  19. Angiogenesis related genes NOS3, CD14, MMP3 and IL4R are associated to VEGF gene expression and circulating levels in healthy adults

    OpenAIRE

    Saleh, Abdelsalam; Stathopoulou, Maria G.; Dadé, Sébastien; Ndiaye, Ndeye Coumba; Azimi-Nezhad, Mohsen; Murray, Helena; Masson, Christine; Lamont, John; Fitzgerald, Peter; Visvikis-Siest, Sophie

    2015-01-01

    Background Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis. The aim was to assess the genetic connections between the angiogenesis-related NOS3, CD14, MMP3, IL4R, IL4 genes and VEGF expression and plasma levels. Methods The associations between VEGF plasma levels with the polymorphisms of NOS3, CD14, MMP3, IL4R, and IL4 were assessed in 403 healthy unrelated adults. The epistatic and environmental interactions were explored, including four VEGF-related polymorphisms...

  20. Distribution of polymorphisms IL4-590 C/T and IL4 RP2 in the human populations of Madeira, Azores, Portugal, Cape Verde and Guinea-Bissau.

    Science.gov (United States)

    Berenguer, Anabela G; Câmara, Rita A; Brehm, António D; Oliveira, Susana; Fernandes, Ana T

    2012-01-01

    The IL4 gene is located on chromosome 5q23.3-31.2. Polymorphisms within this cytokine gene, like the derivative allele T of IL4-590, have been reported as being associated to elevated IgE serum levels and asthma. In the present work, the allelic and genotypic frequency of the IL4-590 and IL4 RP2 polymorphisms was carried out in 599 individuals from Madeira, Azores, Portugal mainland, Cape Verde and Guinea-Bissau and in a sample of 101 asthmatics from Madeira population. In all populations the polymorphisms were in LD and presented a significant dissimilar allelic and genotypic distribution (pMadeira when compared to Azores. Significant differences regarding both loci were found between Madeira population and the group of asthmatics. Genotype 183183TT frequency is higher for African populations while 253253CC prevails in Caucasian populations. The existence of a Hardy-Weinberg Disequilibrium in Guinea-Bissau population not observed in neutral markers leads to the hypothesis of natural selection occurring in these loci probably associated to a rapid population growth an hypothesis strengthened by neutral STRs D5S818 and CSF1PO gene diversity.

  1. Genetic regulation of parasite infection: empirical evidence of the functional significance of an IL4 gene SNP on nematode infections in wild primates

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    Kappeler Peter M

    2011-04-01

    Full Text Available Abstract Background Susceptibility to parasite infection affects fitness-related processes, such as mate choice and survival, yet its genetic regulation remains poorly understood. Interleukin-4 (IL4 plays a central role in the humoral immune defence against nematode parasite infections, inducing IgE switch and regulation of worm expulsion from the intestines. The evolutionary and functional significance of single nucleotide polymorphisms (SNPs in IL4-genes is known, yet empirical information on the effect of IL4 SNPs on gastro-intestinal infections is lacking. Using samples from a population of wild red-fronted lemurs (Eulemur fulvus rufus, Primates: Lemuridae, from western Madagascar, we explored the association of IL4-gene promoter polymorphisms with nematode infections and investigated a possible functional role of the IL4 polymorphism on male reproductive success. Results Using sequence analyses of lemur DNA we detected a new SNP in the IL4 gene promoter area. Carriers of the genotype T/T showed higher nematode infection intensities than individuals of genotypes C/T and C/C. Genetic population analyses using data from more than 10 years, suggested higher reproductive success of T/T males than expected. Conclusions Our results suggest a regulatory effect of an IL4 gene promoter polymorphism on the intensity of parasite infections in a natural population of red-fronted lemurs, with a seemingly disadvantageous genotype represented in low frequencies. Long-term population analyses, however, point in the direction of a negative frequency-dependent association, giving a fitness advantage to the rare genotype. Due to low frequencies of the genotype in question conclusive evidence of a functional role of IL4 polymorphism cannot be drawn here; still, we suggest the use of IL4 polymorphism as a new molecular tool for quick assessment of individual genetic constitution with regard to nematode infection intensities, contributing to a better

  2. Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor.

    Science.gov (United States)

    Ryan, J J; McReynolds, L J; Keegan, A; Wang, L H; Garfein, E; Rothman, P; Nelms, K; Paul, W E

    1996-02-01

    IL-4 causes hematopoietic cells to proliferate and express a series of genes, including CD23. We examined whether IL-4-mediated growth, as measured by 4PS phosphorylation, and gene induction were similarly controlled. Studies of M12.4.1 cells expressing human IL-4R truncation mutants indicated that the region between amino acids 557-657 is necessary for full gene expression, which correlated with Stat6 DNA binding activity. This region was not required for 4PS phosphorylation. Tyrosine-to-phenylalanine mutations in the interval between amino acids 557-657 revealed that as long as one tyrosine remained unmutated, CD23 was fully induced. When all three tyrosines were mutated, the receptor was unable to induce CD23. The results indicate that growth regulation and gene expression are principally controlled by distinct regions of IL-4R.

  3. IL-4-dependent effector phase in autoimmune exocrinopathy as defined by the NOD.IL-4-gene knockout mouse model of Sjögren's syndrome.

    Science.gov (United States)

    Brayer, J B; Cha, S; Nagashima, H; Yasunari, U; Lindberg, A; Diggs, S; Martinez, J; Goa, J; Humphreys-Beher, M G; Peck, A B

    2001-01-01

    NOD mice manifest many features of autoimmune exocrinopathy (Sjögren's syndrome), a disease generally characterized by a chronic, progressive immunological attack against the exocrine tissues of the salivary and lacrimal glands. Previous studies using the NOD congenic partner strain, NOD.Igmu(null), defined an important role for B lymphocytes in the development of xerostomia, implicating autoantibodies reactive with the acetylcholine muscarinic receptor (M3R) as the possible effector mechanism. In the present study, we have examined the impact of the cytokine, interleukin (IL)-4, on autoimmune exocrinopathy by using the IL-4 gene knockout (KO) NOD mouse strain, NOD.IL-4-/-. Despite manifesting the physiological aberrations and marked leukocytic infiltration of the salivary glands characteristic of autoimmune xerostomia in NOD mice, the NOD.IL-4-/- mice do not develop xerostomia. However, NOD.IL-4-/- mice that received adoptively transferred T lymphocytes derived from NOD.Igmu-/- mice progress to xerostomia, thereby reversing the defect. While progression or lack of progression to xerostomia correlated with the ability of the NOD.IL-4-/- mice to express detectable anti-M3R autoantibodies, the precise mechanism of how IL-4 influences the development of autoimmune xerostomia remains speculative.

  4. An atopy-associated polymorphism in the ectodomain of the IL-4R(alpha) chain (V50) regulates the persistence of STAT6 phosphorylation.

    Science.gov (United States)

    Ford, Andrew Q; Heller, Nicola M; Stephenson, Linda; Boothby, Mark R; Keegan, Achsah D

    2009-08-01

    Several commonly occurring polymorphisms in the IL-4R(alpha) have been associated with atopy in humans; the Q576R and the S503P polymorphisms reside in the cytoplasmic domain, whereas the I50 to V50 polymorphism resides in the extracellular domain of the IL-4R(alpha). The effects of these polymorphisms on signaling remain controversial. To determine the effect of the polymorphisms on IL-4 signaling in human cells, we stably transfected the human monocytic cell line U937 with murine IL-4R(alpha) cDNA bearing the I or V at position 50 and the P503/R576 double mutant. Each form of the murine IL-4R(alpha) mediated tyrosine phosphorylation of STAT6 in response to murine IL-4 treatment similar to the induction of tyrosine phosphorylation by human IL-4 signaling through the endogenous human IL-4R(alpha). After IL-4 removal, tyrosine-phosphorylated STAT6 rapidly decayed in cells expressing I50 or P503R576 murine IL-4Ralpha. In contrast, STAT6 remained significantly phosphorylated for several hours after murine IL-4 withdrawal in cells expressing the V50 polymorphism. This persistence in tyrosine-phosphorylated STAT6 was associated with persistence in CIS mRNA expression. Blocking IL-4 signaling during the decay phase using the JAK inhibitor AG490 or the anti-IL-4R(alpha) Ab M1 abrogated the persistence of phosphorylated STAT6 observed in the V50-IL-4R(alpha)-expressing cells. These results indicate that the V50 polymorphism promotes sustained STAT6 phosphorylation and that this process is mediated by continued engagement of IL-4R(alpha), suggesting enhanced responses of V50 IL-4R when IL-4 is limiting.

  5. IL-4 gene expression in adventitial layer (fibrous layer) of hepatic ovine and bovine hydatid cysts.

    Science.gov (United States)

    Dorosti, Zahra; Tolouei, Sepideh; Khanahmad, Hossein; Jafari, Rasool; Jafaee, Fereshteh; Sharafi, Seyedeh Marayam; Darani, Hossein Yousofi

    2016-09-01

    Cystic Echinococcosis is a parasitic disease with cosmopolitan distribution caused by the tape worm Echinococcus granulosus. Fibrous layer is developed around the cyst as a host immune response reaction. The aim of this study was to evaluate the rate of IL-4 gene expression in fibrous layer of bovine and ovine hepatic hydatid cysts using quantitative technique of Real-Time PCR. In this descriptive study the samples of hydatid cyst fibrous layer were taken from 6 bovine and 6 ovine hepatic hydatid cysts. Samples of normal liver tissue close to the cyst were also taken as controls. Total RNA from each sample was extracted and then converted to cDNA. Afterward, the rate of IL-4 gene expression for each sample was evaluated using real-time PCR technique. Data were analyzed by REST software (version 2.0.13, 2009). In sheep the rate of IL-4 gene expression in the fibrous layer of hepatic hydatid cysts was 1.98 times more than the rate of IL4 gene expression in control samples, but the difference was not significant (P = 0.561). In cattle the rate of IL-4 gene expression in the fibrous layer of hepatic hydatid cysts was 9.84 times more than that of control samples which was statistically significant (P layer of bovine hydatid cyst, it can be concluded that this interleukin may play an important role in host parasite relationship.

  6. FREQUENCY DISTRIBUTION OF INTRONIC POLYMORPHISMS OF IL1-raVNTR AND IL-4VNTR IN RHEUMATIC MITRAL VALVE DISEASE IN CAUCASIAN POPULATION OF SIBERIA

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    A. V. Ponasenko

    2015-01-01

    Full Text Available A search for associations between allelic variations of immune response genes, and mitral stenosis associated with rheumatic heart disease, represents an important task when studying the pathogenesis of cardiovascular disorders among inhabitants of large industrial regions in Western Siberia. Among multiple polymorphisms of interleukin-encoding genes, a particular attention should be paid to association studies of some intronic polymorphisms with variable numbers of tandem repeats (VNTR. In this respect, genotyping of interleukin 1 receptor antagonist genes (IL-1ra86bp VNTR and interleukin 4 (IL-470bp VNTR has shown positive associations between the intron 2 IL-1ra*3R/3R microsatellite polymorphism, intron 3 IL-4*2R/2R variant, and the risk of mitral stenosis development in patients with rheumatic heart disease (OR = 12.71; p = 0.0001.  

  7. IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype

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    Guiliano David

    2002-07-01

    Full Text Available Abstract Background "Alternatively-activated" macrophages are found in Th2-mediated inflammatory settings such as nematode infection and allergic pulmonary inflammation. Due in part to a lack of markers, these cells have not been well characterized in vivo and their function remains unknown. Results We have used murine macrophages elicited by nematode infection (NeMφ as a source of in vivo derived alternatively activated macrophages. Using three distinct yet complementary molecular approaches we have established a gene expression profile of alternatively activated macrophages and identified macrophage genes that are regulated in vivo by IL-4. First, genes abundantly expressed were identified by an expressed sequence tag strategy. Second, an array of 1176 known mouse genes was screened for differential expression between NeMφ from wild type or IL-4 deficient mice. Third, a subtractive library was screened to identify novel IL-4 dependent macrophage genes. Differential expression was confirmed by real time RT-PCR analysis. Conclusions Our data demonstrate that alternatively activated macrophages generated in vivo have a gene expression profile distinct from any macrophage population described to date. Several of the genes we identified, including those most abundantly expressed, have not previously been associated with macrophages and thus this study provides unique new information regarding the phenotype of macrophages found in Th2-mediated, chronic inflammatory settings. Our data also provide additional in vivo evidence for parallels between the inflammatory processes involved in nematode infection and allergy.

  8. Basal chromatin modification at the IL-4 gene in helper T cells

    Energy Technology Data Exchange (ETDEWEB)

    Grogan, Jane L.; Wang, Zhi-En; Stanley, Sarah; Harmon, Brian; Loots, Gaby G.; Rubin, Edward M.; Locksley, Richard M.

    2003-04-15

    Chromatin immunoprecipitations in naive CD4, but not CD8, T cells, demonstrated association of the IL-4 promoter with acetylated histone. Histone modifications and rapid IL-4 transcription were absent in conserved noncoding sequence 1 (CNS-1){sup -/-} cells lacking an 8-kb-distant enhancer in the IL-4/IL-13 intergenic region, but also in CD4{sup -/-} and Itk{sup -/-} cells, which have similar Th2 deficiencies. Histones associated with the IL-13 promoter were not similarly acetylated in naive T cells, but became acetylated in differentiated Th2 cells. Conversely, Th1 differentiation induced histone methylation at the type 2 cytokine locus. Like CD4{sup -/-} and Itk{sup -/-} mice, CNS-1{sup -/-} BALB/c mice were highly resistant to the Th2-inducing protozoan, Leishmania major. CNS-1 deficiency led to failure of IL-4 gene repositioning to heterochromatin after Th1 polarization, possibly related to the presence of reiterative Ikaros binding sites in the intergenic element. Hyperacetylation of nonexpressed genes may serve to mark lineage-specific loci for rapid expression and further modification.

  9. Regulation of the Il4 gene is independently controlled by proximal and distal 3' enhancers in mast cells and basophils.

    Science.gov (United States)

    Yagi, Ryouji; Tanaka, Shinya; Motomura, Yasutaka; Kubo, Masato

    2007-12-01

    Mast cells and basophils are known to be a critical interleukin 4 (IL-4) source for establishing Th2 protective responses to parasitic infections. Chromatin structure and histone modification patterns in the Il13/Il4 locus of mast cells were similar to those of IL-4-producing type 2 helper T cells. However, using a transgenic approach, we found that Il4 gene expression was distinctly regulated by individual cis regulatory elements in cell types of different lineages. The distal 3' element contained conserved noncoding sequence 2 (CNS-2), which was a common enhancer for memory phenotype T cells, NKT cells, mast cells, and basophils. Targeted deletion of CNS-2 compromised production of IL-4 and several Th2 cytokines in connective-tissue-type and immature-type mast cells but not in basophils. Interestingly, the proximal 3' element containing DNase I-hypersensitive site 4 (HS4), which controls Il4 gene silencing in T-lineage cells, exhibited selective enhancer activity in basophils. These results indicate that CNS-2 is an essential enhancer for Il4 gene transcription in mast cell but not in basophils. The transcription of the Il4 gene in mast cells and basophils is independently regulated by CNS-2 and HS4 elements that may be critical for lineage-specific Il4 gene regulation in these cell types.

  10. Angiogenesis related genes NOS3, CD14, MMP3 and IL4R are associated to VEGF gene expression and circulating levels in healthy adults.

    Science.gov (United States)

    Saleh, Abdelsalam; Stathopoulou, Maria G; Dadé, Sébastien; Ndiaye, Ndeye Coumba; Azimi-Nezhad, Mohsen; Murray, Helena; Masson, Christine; Lamont, John; Fitzgerald, Peter; Visvikis-Siest, Sophie

    2015-10-05

    Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis. The aim was to assess the genetic connections between the angiogenesis-related NOS3, CD14, MMP3, IL4R, IL4 genes and VEGF expression and plasma levels. The associations between VEGF plasma levels with the polymorphisms of NOS3, CD14, MMP3, IL4R, and IL4 were assessed in 403 healthy unrelated adults. The epistatic and environmental interactions were explored, including four VEGF-related polymorphisms previously identified. The VEGF expression in peripheral blood mononuclear cells was quantified (n = 65) for the VEGF121, VEGF145, VEGF165, and VEGF189 isoforms. The polymorphism rs1799983 of NOS3 was associated with the sum of all VEGF isoforms mRNA levels (P = 0.032) and VEGF145 (P = 0.033). Rs1800779 of NOS3 interacted with rs3918226 of the same gene and with the rs2569190 of CD14 (P = 0.022, P = 0.042, respectively) for VEGF plasma levels. Other epistatic interactions included the rs1801275 of IL4R with the rs6921438 (VEGF-related variant) and rs3025058 of MMP3 (P = 0.042, P = 0.010 respectively) and the rs2569190 of CD14 with the rs3025058 of MMP3 (P = 0.0119). We also identified an interaction of rs1800779 with obesity, high-density lipoprotein cholesterol and triglycerides (P = 0.018, P = 0.005, P = 0.043, respectively) as well as the interaction of rs6921438 with hypertension (P = 0.028). Our findings indicated that genetic variants of NOS3, CD14, MMP3 and IL4R are implicated in the determination of VEGF expression and plasma levels. Thus, they support the hypothesis that in physiological conditions there are complex biological relationships between pathways (such as angiogenesis and inflammation), which are involved in the development of chronic diseases.

  11. Four-locus gene interaction between IL13, IL4, FCER1B, and ADRB2 for asthma in Chinese Han children.

    Science.gov (United States)

    Hua, Li; Zuo, Xian-Bo; Bao, Yi-Xiao; Liu, Quan-Hua; Li, Jing-Yang; Lv, Jie; Fang, Ding-Zhu; Lin, Qian; Bao, Jun; Ji, Ruo-Xu

    2016-04-01

    IL13, IL4, IL4RA, FCER1B, and ADRB2 are important inflammatory genes associated with immunoglobulin E levels. This study attempts to determine whether there are gene-gene interactions in the five genes among asthmatic children of Chinese Han nationality. Nine single-nucleotide polymorphisms (SNPs) in the five genes were genotyped in 1,000 asthmatic children and 1,000 healthy controls using TaqMan real-time quantitative polymerase chain reaction. Multifactor-dimensionality reduction method was applied for the analysis. A four-way gene-gene interaction model consisting of IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was chosen as the optimal one for determining asthma susceptibility (testing balanced accuracy = 0.6089, cross-validation consistency = 10/10, P = 6.98E-05). Each of the four SNPs was identified to have an independent association with childhood asthma (G allele of rs20541, odds ratio (OR) = 1.24, P = 1.23E-03; T allele of rs2243250, OR = 1.25, P = 3.81E-03; A allele of rs1042713, OR = 1.29, P = 6.75E-05; G allele of rs569108, OR = 1.27, P = 3.86E-03). Individuals homozygous for the risk alleles at all the four loci (rs20541 GG, rs2243250 TT, rs1042713 AA, and rs569108 GG) had a significantly higher risk of asthma compared with those without any risk homozygotes (OR = 13.55, P = 4.28E-03), and also greater than those with less than four risk homozygotes (OR = 10.09, P = 6.51E-03). Our results suggest that IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108, four SNPs with significant sole effect on asthma, interact to confer a higher risk for the disease in Chinese Han children. © 2015 Wiley Periodicals, Inc.

  12. Regulation of the Il4 Gene Is Independently Controlled by Proximal and Distal 3′ Enhancers in Mast Cells and Basophils▿

    OpenAIRE

    Yagi, Ryouji; Tanaka, Shinya; Motomura, Yasutaka; Kubo, Masato

    2007-01-01

    Mast cells and basophils are known to be a critical interleukin 4 (IL-4) source for establishing Th2 protective responses to parasitic infections. Chromatin structure and histone modification patterns in the Il13/Il4 locus of mast cells were similar to those of IL-4-producing type 2 helper T cells. However, using a transgenic approach, we found that Il4 gene expression was distinctly regulated by individual cis regulatory elements in cell types of different lineages. The distal 3′ element con...

  13. [The character of the morphological changes of the mucous membrane of the large intestine and the genetic polymorphism of IL-1RA, IL-1B, IL-4 TNFA in patient with irritable bowel syndrome].

    Science.gov (United States)

    Sarsenbaeva, A S; Ivanova, E L; Burmistrova, A L; Drozdov, I V

    2013-01-01

    The aim of this study was to evaluate the presence or absence of a relationship between the variants of the course of IBS and their association with genetic polymorphisms of genes and intergenic interaction of cytokines. The sample consisted of 81 patients, the diagnosis was verified according to the criteria of the Rome III, were isolated psychopathological, morphological complications, extra-intestinal symptoms. Polymorphism genotyping IL-1Ra, IL-b, IL-4, TNFa performed by PCR. Statistical treatment are a non-parametric analysis of multiple comparisons, hierarchical log-linear analysis. It is found out the relation between the clinical variants with morphological changes of the mucous membrane of the large intestine, the association between gender characteristics of patients with IBS is established and with genetic polymorphisms of cytokines.

  14. Early IL-4 gene expression in abomasum is associated with resistance to Haemonchus contortus in hair and wool sheep breeds.

    Science.gov (United States)

    Jacobs, J R; Sommers, K N; Zajac, A M; Notter, D R; Bowdridge, S A

    2016-06-01

    Early immune events associated with reduced larval burden remain unclear in parasite-resistant breeds of sheep. Therefore, our objective was to determine breed differences in immune-related gene expression following infection with H. contortus. Gene expression in abomasal tissue and mucosa and in abomasal lymph nodes (ALN) was measured in 24 St. Croix (hair) lambs and 24 Dorset x (Finn-Rambouillet) (wool) lambs at 0 (uninfected), 3, 5 and 7 days after infection with 10 000 L3 H. contortus larvae. Expression of IL-4 in abomasal mucosa was detected on day 3 and increased to day 7 in hair lambs, but was not detectable in wool lambs. Genes that recruit neutrophils (CXCL1) and macrophages (MCP1) were upregulated in abomasal mucosa of hair lambs. Genes associated with alternative macrophage activation (ARG-1) and eosinophil activation (Gal-14) were also upregulated in the abomasal mucosa of hair lambs. Tissue remodeling genes (MMP13, PDGF) and tumour necrosis factor alpha (TNF-α) and MCP1 were upregulated in abomasal tissue of wool lambs; these lambs also had greater expression of forkhead box P3 in ALN. These data indicate a role for early IL-4 expression locally and demonstrate potential downregulation of immunity in wool sheep that could facilitate establishment of H. contortus.

  15. Association of IL-4RA single nucleotide polymorphisms, HLA-DR and HLA-DQ in children with Alternaria-sensitive moderate-severe asthma.

    Science.gov (United States)

    Knutsen, Alan P; Vijay, Hari M; Kariuki, Barbara; Santiago, Luis A; Graff, Ralph; Wofford, Jonathan D; Shah, Maulik R

    2010-03-18

    Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked Alternaria sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying Alternaria sensitivity and asthma, in these studies we examined T cell responses to Alternaria antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma. Sixty children with Alternaria-sensitive moderate-severe asthma were compared to 49 children with Alternaria-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in Alternaria-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 Alternaria-specific T-cells, cultures were stimulated in media alone, Alternaria alternata extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up-regulation of CD23 on B cells. Children with Alternaria-sensitive moderate-severe asthma trended to have increased sensitivities to Cladosporium (46% versus 35%), to Aspergillus (43% versus 28%), and significantly increased sensitivities to trees (78% versus 57%) and to weeds (68% versus 48%). The IL-4RA ile75val polymorphism was significantly increased in Alternaria-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency) compared to Alternaria-sensitive mild asthmatics, 57% (0.388 allele frequency). This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL-4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of Alternaria-sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics to Alternaria extract and Alt a1 stimulation. The frequency of HLA-DQB1*03 allele was significantly decreased in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics, 39

  16. Association of IL-4RA single nucleotide polymorphisms, HLA-DR and HLA-DQ in children with Alternaria-sensitive moderate-severe asthma

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    Santiago Luis A

    2010-03-01

    Full Text Available Abstract Background Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked Alternaria sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying Alternaria sensitivity and asthma, in these studies we examined T cell responses to Alternaria antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma. Methods Sixty children with Alternaria-sensitive moderate-severe asthma were compared to 49 children with Alternaria-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in Alternaria-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 Alternaria-specific T-cells, cultures were stimulated in media alone, Alternaria alternata extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up-regulation of CD23 on B cells. Results Children with Alternaria-sensitive moderate-severe asthma trended to have increased sensitivities to Cladosporium (46% versus 35%, to Aspergillus (43% versus 28%, and significantly increased sensitivities to trees (78% versus 57% and to weeds (68% versus 48%. The IL-4RA ile75val polymorphism was significantly increased in Alternaria-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency compared to Alternaria-sensitive mild asthmatics, 57% (0.388 allele frequency. This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL-4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of Alternaria-sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics to Alternaria extract and Alt a1 stimulation. The frequency of HLA-DQB1*03 allele was significantly decreased in Alternaria-sensitive moderate

  17. IL-4 Up-Regulates MiR-21 and the MiRNAs Hosted in the CLCN5 Gene in Chronic Lymphocytic Leukemia.

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    Natalia Ruiz-Lafuente

    Full Text Available Interleukin 4 (IL-4 induces B-cell differentiation and survival of chronic lymphocytic leukemia (CLL cells. MicroRNAs (miRNAs regulate mRNA and protein expression, and several miRNAs, deregulated in CLL, might play roles as oncogenes or tumor suppressors. We have studied the miRNA profile of CLL, and its response to IL-4, by oligonucleotide microarrays, resulting in the detection of a set of 129 mature miRNAs consistently expressed in CLL, which included 41 differentially expressed compared to normal B cells (NBC, and 6 significantly underexpressed in ZAP-70 positive patients. IL-4 stimulation brought about up-regulation of the 5p and 3p mature variants of the miR-21 gene, which maps immediately downstream to the VMP1 gene, and of the mature forms generated from the miR-362 (3p and 5p, miR-500a (3p, miR-502 (3p, and miR-532 (3p and 5p genes, which map within the third intron of the CLCN5 gene. Both genes are in turn regulated by IL-4, suggesting that these miRNAs were regulated by IL-4 as passengers from their carrier genes. Their levels of up-regulation by IL-4 significantly correlated with cytoprotection. MiR-21 has been reported to be leukemogenic, associated to bad prognosis in CLL, and the miRNA more frequently overexpressed in human cancer. Up-regulation by IL-4 of miR-21 and the miRNAs hosted in the CLCN5 locus may contribute to evasion of apoptosis of CLL cells. These findings indicate that the IL-4 pathway and the miRNAs induced by IL-4 are promising targets for the development of novel therapies in CLL.

  18. Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma.

    Science.gov (United States)

    Tachdjian, Raffi; Mathias, Clinton; Al Khatib, Shadi; Bryce, Paul J; Kim, Hong S; Blaeser, Frank; O'Connor, Brian D; Rzymkiewicz, Danuta; Chen, Andrew; Holtzman, Michael J; Hershey, Gurjit K; Garn, Holger; Harb, Hani; Renz, Harald; Oettgen, Hans C; Chatila, Talal A

    2009-09-28

    Polymorphisms in the interleukin-4 receptor alpha chain (IL-4R alpha) have been linked to asthma incidence and severity, but a causal relationship has remained uncertain. In particular, a glutamine to arginine substitution at position 576 (Q576R) of IL-4R alpha has been associated with severe asthma, especially in African Americans. We show that mice carrying the Q576R polymorphism exhibited intense allergen-induced airway inflammation and remodeling. The Q576R polymorphism did not affect proximal signal transducer and activator of transcription (STAT) 6 activation, but synergized with STAT6 in a gene target- and tissue-specific manner to mediate heightened expression of a subset of IL-4- and IL-13-responsive genes involved in allergic inflammation. Our findings indicate that the Q576R polymorphism directly promotes asthma in carrier populations by selectively augmenting IL-4R alpha-dependent signaling.

  19. Chromosome 5q candidate genes in coeliac disease: genetic variation at IL4, IL5, IL9, IL13, IL17B and NR3C1.

    Science.gov (United States)

    Ryan, A W; Thornton, J M; Brophy, K; Daly, J S; McLoughlin, R M; O'Morain, C; Abuzakouk, M; Kennedy, N P; Stevens, F M; Feighery, C; Kelleher, D; McManus, R

    2005-02-01

    Genetic predisposition to coeliac disease (CD) is determined primarily by alleles at the HLA-DQB locus, and evidence exists implicating other major histocompatibility complex-linked genes (6p21) and the CTLA4 locus on chromosome 2q33. In addition, extensive family studies have provided strong, reproducible evidence for a susceptibility locus on chromosome 5q (CELIAC2). However, the gene responsible has not been identified. We have assayed genetic variation at the IL4, IL5, IL9, IL13, IL17B and NR3C1 (GR) loci, all of which are present on chromosome 5q and have potential or demonstrated involvement in autoimmune and/or inflammatory disease, in a sample of 409 CD cases and 355 controls. Thirteen single nucleotide polymorphisms were chosen on the basis of functional relevance, prior disease association and, where possible, prior knowledge of the haplotype variation present in European populations. There were no statistically significant allele or haplotype frequency differences between cases and controls. Therefore, these results provide no evidence that these loci are associated with CD in this sample population.

  20. Significance of CYCLOOXYGENASE-2(COX-2), PERIOSTIN (POSTN) and INTERLEUKIN-4(IL-4) gene expression in the pathogenesis of chronic rhinosinusitis with nasal polyps.

    Science.gov (United States)

    Miłoński, Jarosław; Zielińska-Bliźniewska, Hanna; Przybyłowska, Karolina; Pietkiewicz, Piotr; Korzycka-Zaborowska, Barbara; Majsterek, Ireneusz; Olszewski, Jurek

    2015-12-01

    The purpose of this paper was to evaluate the level of Cyclooxygenase-2 (COX-2), Periostin (POSTN) and Interleukin-4(IL-4) gene expression in patients with chronic rhinosinusitis with nasal polyps, without polyps and with a nasal septum deviation. The tests were performed on 63 patients (24 women and 39 men) with chronic rhinosinusitis and polyps (CRSwP-study group I), with determination of the COX-2, POSTN and IL-4 gene expression; an allergy was diagnosed in 38 cases. The reference groups were patients with chronic rhinosinusitis without polyps--CRS (n = 23, including 14 women and 9 men) and patients with nasal septum deviation--DSN (n = 18, including 9 women and 9 men). The expression level was determined in the polyp tissue and the mucosa of paranasal sinus collected during an FESS. The expression level of studied genes was also evaluated in the material. Immediately after being collected, the tissue fragments were placed in test tubes with 1 ml of RNAlater (Qiagen, Hilden, Germany) preventing the degradation of RNA and frozen at -70 °C. The studies revealed an increased level of POSTN, IL-4 gene expression and a decreased level of COX-2 gene expression that may be associated with the development of chronic rhinosinusitis with nasal polyps. An analysis of the expression level indicates the participation of POSTN and IL-4 in the development of chronic rhinosinusitis with nasal polyps in patients with atopy.

  1. Association of Interleukin-4 Receptor Gene Polymorphism with Chronic Periodontitis

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    M. Khoshhal

    2011-10-01

    Full Text Available Introduction & Objective: Periodontitis is a multifactorial disease in which host immune system and genetic factors have an important role in its pathogenesis. Genetic polymorphisms in cytokines and their receptors have been proposed as potential markers for periodontal diseases. The aim of the present study was to evaluate whether IL-4R gene polymorphism is associated with chronic periodontitis (CP or not? Materials & Methods: In this cross sectional study ninety non smoker patients (61 women and 29 men with chronic periodontitis were selected according to established criteria. They were categorized into three groups according to their clinical attachment level (CAL. Mutation at position 375(alanine/glutamine, 411(leucine/serine, 478(serine/proline, 406 (arginine/ cysteine in the IL-4R gene was detected by a polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP method.Results: The distribution of mutations for IL-4 polymorphism at amino acids 375 (P=0.41, 411(P=0.22, 478(P=0.17, 406(P=0.77 were not significantly different among mild, moderate and sever chronic periodontitis patients. Conclusion: This study suggests that there is no correlation between IL-4R polymorphism of chronic periodontitis.(Sci J Hamadan Univ Med Sci 2011;18(3:63-69

  2. Association of interleukin genes polymorphism with asthma susceptibility in Indian children: a case-control study.

    Science.gov (United States)

    Dixit, Pratibha; Awasthi, Shally; Agarwal, Sarita

    2015-01-01

    Interleukins (IL) 4 and 13 genes and their receptors (R) are the key cytokines which amplify inflammatory reactions in asthma. This study aimed to investigate the association of IL 4, 4 R, 13 and 13 R genes polymorphism with asthma in Indian children. In this hospital-based case-control study, included were children aged 1-15 years recruited as diagnosed cases of bronchial asthma, according to EPR 2007 and excluded were subjects with other respiratory diseases. Children with no present or past history of asthma were enrolled as controls. Spirometry was done in cases age ≥ 6 years. Gene-gene interaction was evaluated using binary logistic regression. From October 2010 to July 2013, 275 cases and 275 controls were recruited. Gene-gene interactions between C1112T in IL 13 and Ile50Val in IL 4 R gene polymorphisms were found to be statistically significant (OR = 2.37, 95% CI = 1.04-5.42, p = 0.040). Individuals with CT and GG genotype of C1112T in IL 13 and Ile50Val in IL 4 R were at twice the risk for the development of asthma compared to individuals with both non-risk genotypes. The data suggests that gene-gene interactions between IL 13 and IL 4 R genes may play an important role in asthma among Indian children.

  3. Angiogenin gene polymorphism

    Institute of Scientific and Technical Information of China (English)

    Hongli Wang; Dongsheng Fan; Yingshuang Zhang

    2013-01-01

    Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we se-quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mel itus (129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy pa-tients) and 268 healthy controls. Al subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistical y significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China.

  4. Gene Polymorphisms in Chronic Periodontitis

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    Marja L. Laine

    2010-01-01

    Full Text Available 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 polymorphism. Candidate gene polymorphism studies with a case-control design and reported genotype frequencies in CP patients were searched and reviewed. There is growing evidence that polymorphisms in the IL1, IL6, IL10, vitamin D receptor, and CD14 genes may be associated with CP in certain populations. However, carriage rates of the rare (-allele of any polymorphism varied considerably among studies and most of the studies appeared under-powered and did not correct for other risk factors. Larger cohorts, well-defined phenotypes, control for other risk factors, and analysis of multiple genes and polymorphisms within the same pathway are needed to get a more comprehensive insight into the contribution of gene polymorphisms in CP.

  5. Essential role of Stat6 in IL-4 signalling.

    Science.gov (United States)

    Takeda, K; Tanaka, T; Shi, W; Matsumoto, M; Minami, M; Kashiwamura, S; Nakanishi, K; Yoshida, N; Kishimoto, T; Akira, S

    1996-04-18

    Interleukin-4 (IL-4) is a pleiotropic lymphokine which plays an important role in the immune system. IL-4 activates two distinct signalling pathways through tyrosine phosphorylation of Stat6, a signal transducer and activator of transcription, and of a 170K protein called 4PS. To investigate the functional role of Stat6 in IL-4 signalling, we generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice, expression of CD23 and major histocompatibility complex (MHC) class II in resting B cells was not enhanced in response to IL-4. IL-4 induced B-cell proliferation costimulated by anti-IgM antibody was abolished. The T-cell proliferative response was also notably reduced. Furthermore, production of Th2 cytokines from T cells as well as IgE and IgG1 responses after nematode infection were profoundly reduced. These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses.

  6. Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review

    Directory of Open Access Journals (Sweden)

    Cross SS

    2006-07-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  7. Identification and Characterization of a Novel IL-4 Receptor α Chain (IL-4Rα Antagonist to Inhibit IL-4 Signalling

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    Nayyar Ahmed

    2015-05-01

    Full Text Available Background/Aims: In recent times, allergy has become a financial, physical and psychological burden to the society as a whole. In allergic cascades, cytokine IL-4 binds to IL-4 receptor (IL-4R, consequently producing allergen-specific IgE antibodies by B cells. In addition, among other functions, IL-4 is also responsible for B and T cell proliferation and differentiation. Hence, characterization of novel antagonists that inhibit IL-4 signalling forms the overall aim of this study. Methods: Phage display was used to screen a random 12-mer synthetic peptide library with a human IL-4Rα to identify peptide candidates. Once identified, the peptides were commercially synthesized and used for in vitro immunoassays. Results: We have successfully used phage display to identify M13 phage clones that demonstrated specific binding to IL-4Rα. The peptide N1 was synthesized for use in ELISA, demonstrating significant binding to IL-4Rα and inhibiting interaction with cytokine IL-4. Furthermore, the peptide was tested in a transfected HEK-Blue IL-4 reporter cell line model, which produces alkaline phosphatase (AP. QUANTI-Blue, a substrate, breaks down in the presence of AP producing a blue coloration. Using this colorimetric analysis, >50% inhibition of IL-4 signalling was achieved. Conclusion: We have successfully identified and characterised a synthetic peptide antagonist against IL-4Rα, which effectively inhibits IL-4 interaction with the IL-4Rα in vitro. Since IL-4 interaction with IL-4Rα is a common pathway for many allergies, a prophylactic treatment can be devised by inhibiting this interaction for future treatment of allergies.

  8. Effects of β-d-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, RORγt, IL4 and GATA3 gene expressions in rheumatoid arthritis patients

    Science.gov (United States)

    Barati, Anis; Jamshidi, Ahmad Reza; Ahmadi, Hossein; Aghazadeh, Zahra; Mirshafiey, Abbas

    2017-01-01

    Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of β-d-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4) has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the expression levels of IL4, GATA3, IL17 and RORγt. The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease IL17 and RORγt levels but also increase IL4 and GATA3 levels after 12 weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier: IRCT2014011213739N2).

  9. Autoimmune Hepatitis in Brazilian Children: IgE and Genetic Polymorphisms in Associated Genes

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    Léa Campos de Oliveira

    2015-01-01

    Full Text Available Pediatric autoimmune hepatitis (AIH patients present hypergammaglobulinemia, periportal CD8+ cytotoxic T cell infiltration, and cirrhosis. Autoantibody profile defines AIH types 1 and 2 in addition to strong association with HLA-DRB1. We previously detected increased IgE serum levels and sought to compare clinical and histological features according to IgE levels in AIH (n=74, ages 1–14 years patients. Additionally, we typed 117 patients and 227 controls for functional polymorphisms of IL4, IL13, IL5, and IL4RA genes involved in IgE switching and eosinophil maturation that might contribute to overall genetic susceptibility to AIH. Serum IgE levels were high in 55% of AIH-1, but only in 12% of AIH-2 (P=0.003 patients. Liver IgE was present in 91.3% of AIH-1 patients. The A alleles at both IL13 rs20541 and IL4RA rs1805011 were associated with AIH-1 (P=0.024, OR = 1.55 and P<0.0001, OR = 2.15, resp.. Furthermore, individuals presenting homozygosis for the A allele at IL4RA rs1805011 and HLA-DRB103∗ and/or 13∗ allele had sixfold greater risk to develop the disease (OR = 14.00, P<0.001. The novel association suggests an additional role for IgE-linked immune response genes in the pathogenesis of AIH.

  10. Leptin gene polymorphisms and their phenotypic associations

    NARCIS (Netherlands)

    Lende, van der T.; Pas, te M.F.W.; Veerkamp, R.F.; Liefers, S.C.

    2005-01-01

    In an era of rapidly increasing prevalence of human obesity and associated health problems, leptin gene polymorphisms have drawn much attention in biomedical research. Leptin gene polymorphisms have furthermore drawn much attention from animal scientists for their possible roles in economically impo

  11. Leptin gene polymorphisms and their phenotypic associations

    NARCIS (Netherlands)

    Lende, van der T.; Pas, te M.F.W.; Veerkamp, R.F.; Liefers, S.C.

    2005-01-01

    In an era of rapidly increasing prevalence of human obesity and associated health problems, leptin gene polymorphisms have drawn much attention in biomedical research. Leptin gene polymorphisms have furthermore drawn much attention from animal scientists for their possible roles in economically

  12. T helper-2 cytokine/regulatory T-cell gene polymorphisms and their relation with risk of psoriasis in a South Indian Tamil cohort.

    Science.gov (United States)

    Indhumathi, Sundar; Rajappa, Medha; Chandrashekar, Laxmisha; Ananthanarayanan, Palghat Hariharan; Thappa, Devinder Mohan; Negi, Vir Singh

    2017-02-01

    Psoriasis is known to be associated with an up-regulation of T-helper (Th)-1 & Th-17 cytokines and a relative down-regulation of Th-2 and T-regulatory (T-reg) cytokines. Certain allelic variants of these cytokine genes may alter Th1/Th17 and Th2/T-reg balance and may be associated with the risk of psoriasis. Hence we aimed to determine the association of IL-4 (rs2243250), IL-10 (rs1800871 and rs1800896) and FOXP3 (rs3761548) gene polymorphisms with risk of psoriasis in South Indian Tamils. A total of 360 cases of psoriasis and 360 healthy controls were recruited. The polymorphism in IL-4 (rs2243250) & IL-10 (rs1800871) were typed by ARMS-PCR and IL-10 (rs1800896) & FOXP3 (rs3761548) were typed by TaqMan 5'allele discrimination assay. We observed that IL-4 (rs2243250) had a reduced risk of psoriasis, while the IL-10 (rs1800871) conferred an increased susceptibility to psoriasis, as compared with controls. However, IL-10 (rs1800896) and FOXP3 (rs3761548) gene polymorphisms were not associated with psoriasis risk. The plasma IL-4 levels was not different between the cases and controls, however the heterozygous CT genotype demonstrated significant high IL-4 levels. Plasma IL-10 levels were significantly increased in cases compared to controls, however none of the genotypes were associated with the plasma IL-10 levels. Our results suggest that IL-4 (rs2243250) polymorphism is protective against psoriasis, while IL-10 (rs1800871) polymorphism confers increased risk of psoriasis in South Indian Tamils. Detection of these genetic variants as predictive risk factors may lead to the selection of patient-tailored therapy to maximize the effectiveness of therapy. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  13. Association Between IL-4 and IL-6 Expression Variants and Gastric Cancer Among Portuguese Population

    Directory of Open Access Journals (Sweden)

    Ana Maria Sampaio

    2015-07-01

    Conclusion: IL-6 and IL-4 expression variants seem to have an important role in GC risk mechanisms. This study provides preliminary evidence that IL-4 and IL-6 polymorphisms, although not directly linked to the disease, may be useful tools in the study of this multifactorial disease.

  14. Effects of β-D-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, RORγt, IL4 and GATA3 gene expressions in rheumatoid arthritis patients

    Directory of Open Access Journals (Sweden)

    Barati A

    2017-03-01

    Full Text Available Anis Barati,1 Ahmad Reza Jamshidi,2,* Hossein Ahmadi,1 Zahra Aghazadeh,1 Abbas Mirshafiey1,* 1Department of Immunology, School of Public Health, 2Iranian Institute for Health Sciences Research, Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran *These authors contributed equally to this work Abstract: Rheumatoid arthritis (RA is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs and biological drugs can interfere with the disease process. In this study, the effect of β-D-mannuronic acid (M2000 as a novel non-steroidal anti-inflammatory drug (NSAID with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4 has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs were collected before and after treatment to evaluate the expression levels of IL4, GATA3, IL17 and RORγt. The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease IL17 and RORγt levels but also increase IL4 and GATA3 levels after 12 weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier

  15. Allelic polymorphisms in the repeat and promoter regions of the interleukin-4 gene and malaria severity in Ghanaian children

    DEFF Research Database (Denmark)

    Gyan, B A; Goka, B; Cvetkovic, J T

    2004-01-01

    Immunoglobulin E has been associated with severe malaria suggesting a regulatory role for interleukin (IL)-4 and/or IgE in the pathogenesis of severe malaria. We have investigated possible associations between polymorphisms in the IL-4 repeat region (intron 3) and promoter regions (IL-4 +33CT and...

  16. Association between polymorphisms in selected inflammatory response genes and the risk of prostate cancer

    Directory of Open Access Journals (Sweden)

    Chen J

    2016-01-01

    Full Text Available Jun Chen,1,* Xue-Ming Ying,2,* Xue-Ming Huang,3 Peng Huang,4 Shao-Cong Yan1 1Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, 2Department of Oncology, Jingdezhen City People’s Hospital, Jingdezhen, 3Department of Urology, Research Institute, The First Affiliated Hospital of Nanchang University, 4The Medical School of Nanchang University, School of Public Health, Nanchang, People’s Republic of China*These authors contributed equally to this workAbstract: Inflammation represents an important event which facilitates prostate carcinogenesis. Genetic variations in inflammatory response genes could affect the level and function of the protein products, resulting in the differential prostate cancer risk among carriers of different variants. This study attempted to investigate the association of IL-4 rs2243250, IL-6 rs10499563, IL-8 rs4073, as well as NFKBIA rs2233406 and rs3138053 polymorphisms with prostate cancer risk in the Chinese population. Genotyping of the polymorphisms was performed by using polymerase chain reaction-restriction fragment length polymorphism technique on 439 prostate cancer patients and 524 controls, and the association of each polymorphic genotype with prostate cancer risk was evaluated by using logistic regression analysis based on allele, heterozygous, and homozygous comparison models, with adjustment to age and smoking status. We showed that the C allele of IL-4 rs2243250 polymorphism could increase prostate cancer risk (heterozygous comparison model: odds ratio [OR] =1.434, 95% confidence interval [CI] =1.092–1.881, P=0.009; homozygous comparison model: OR =2.301, 95% CI =1.402–3.775, P=0.001; allele comparison model: OR =1.509, 95% CI =1.228–1.853, P<0.001. On the other hand, the C allele of rs10499563 polymorphism could decrease prostate cancer risk (heterozygous comparison model: OR =0.694, 95% CI =0.525–0.918, P=0.010; homozygous comparison model: OR =0.499, 95% CI =0

  17. Association Between Interleukin 4 Gene Seventy-Base-Pair Variable Number of Tandem Repeats Polymorphism and Uterine Leiomyoma

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    Salimi

    2014-06-01

    Full Text Available Background Uterine Leiomyoma (UL is the most common gynecological tumor and a public health problem. Higher serum interleukin 4 (IL-4 level, as an anti-inflammatory cytokine that regulates TH1/TH2 cells balance, has been observed in the uterine cavity. Objectives The aim of this study was to investigate the association between IL4 gene variable number of tandem repeats (VNTR polymorphism and the risk of UL in southeast of Iran. Patients and Methods We compared of 99 patients with UL with that of 102 healthy controls. The IL4 VNTR polymorphism was genotyped by gel electrophoresis after PCR amplification. Results There was no significant association between RP*1/RP*2 and RP*2/RP*2 genotypes and UL; however, a significant association between RP*2/RP*2 genotype and UL was found after adjustment for age (OR, 4; 95% CI, 1.3-12.4; and P = 0.015. The frequency of RP*2 allele was significantly higher in women with UL (OR, 1.9; 95% CI, 1.1-3.5; and P = 0.03. Conclusions The IL4 VNTR RP*2/RP*2 genotype could be an age-related risk factor for UL. Moreover, the frequency of RP*2 allele was significantly higher in women with UL.

  18. A STAT6 gene polymorphism is associated with high infection levels in urinary schistosomiasis.

    Science.gov (United States)

    He, H; Isnard, A; Kouriba, B; Cabantous, S; Dessein, A; Doumbo, O; Chevillard, C

    2008-04-01

    Th2-mediated immunity is critical for human defence against schistosome, and susceptibility to infection is controlled by a major genetic locus, mapped on the 5q31-q33 region comprising the genes IL4, IL5 and IL13. We have reported an association between the rs1800925 polymorphism in the IL13 promoter and infection levels in a Dogon population (693 subjects in Ségué and 148 in Boul), where Schistosoma haematobium is endemic. In the same population, we investigated whether other polymorphisms in genes involved in type 2 cytokine immune response could affect susceptibility to schistosome infection. By logistic regression analysis, we found an association between a single-nucleotide polymorphism (SNP) in the STAT6 gene (rs324013) and infection levels (P=0.04). We confirmed this association in analyses restricted to subjects under 20 years age and living in Boul, the village with the highest levels of infection (P=0.005). We detected an additive effect of the rs324013 and rs1800925 polymorphisms (P=0.011). These SNPs were not strongly correlated with any other tested markers surrounding the two genes. Furthermore, electrophoretic mobility shift assay has shown that both polymorphisms affect transcription factor binding. These results are consistent with the Th2 cytokine pathway enhancing resistance to schistosome infection in humans.

  19. Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study

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    de Vogel Lisette

    2011-03-01

    Full Text Available Abstract Background Various cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA. We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA. Methods Polymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-α treatment as a marker of RA severity was assessed. Results The IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity. Conclusions We here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA.

  20. FRNK negatively regulates IL-4-mediated inflammation.

    Science.gov (United States)

    Sharma, Ritu; Colarusso, Pina; Zhang, Hong; Stevens, Katarzyna M; Patel, Kamala D

    2015-02-15

    Focal adhesion kinase (FAK)-related nonkinase (PTK2 isoform 6 in humans, hereafter referred to as FRNK) is a cytoskeletal regulatory protein that has recently been shown to dampen lung fibrosis, yet its role in inflammation is unknown. Here, we show for the first time that expression of FRNK negatively regulates IL-4-mediated inflammation in a human model of eosinophil recruitment. Mechanistically, FRNK blocks eosinophil accumulation, firm adhesion and transmigration by preventing transcription and protein expression of VCAM-1 and CCL26. IL-4 activates STAT6 to induce VCAM-1 and CCL26 transcription. We now show that IL-4 also increases GATA6 to induce VCAM-1 expression. FRNK blocks IL-4-induced GATA6 transcription but has little effect on GATA6 protein expression and no effect on STAT6 activation. FRNK can block FAK or Pyk2 signaling and we, thus, downregulated these proteins using siRNA to determine whether signaling from either protein is involved in the regulation of VCAM-1 and CCL26. Knockdown of FAK, Pyk2 or both had no effect on VCAM-1 or CCL26 expression, which suggests that FRNK acts independently of FAK and Pyk2 signaling. Finally, we found that IL-4 induces the late expression of endogenous FRNK. In summary, FRNK represents a novel mechanism to negatively regulate IL-4-mediated inflammation.

  1. T-Cell Cytokine Gene Polymorphisms and Vitamin D Pathway Gene Polymorphisms in End-Stage Renal Disease due to Type 2 Diabetes Mellitus Nephropathy: Comparisons with Health Status and Other Main Causes of End-Stage Renal Disease

    Directory of Open Access Journals (Sweden)

    Alicja E. Grzegorzewska

    2014-01-01

    Full Text Available Background. T-cell cytokine gene polymorphisms and vitamin D pathway gene polymorphisms were evaluated as possibly associated with end-stage renal disease (ESRD resulting from type 2 diabetes mellitus (DM nephropathy. Methods. Studies were conducted among hemodialysis (HD patients with ESRD due to type 2 DM nephropathy, chronic glomerulonephritis, chronic infective tubulointerstitial nephritis, and hypertensive nephropathy as well as in healthy subjects. A frequency distribution of T-cell-related interleukin (IL genes (IL18 rs360719, IL12A rs568408, IL12B rs3212227, IL4R rs1805015, IL13 rs20541, IL28B rs8099917, IL28B, and rs12979860 and vitamin D pathway genes (GC genes: rs2298849, rs7041, and rs1155563; VDR genes: rs2228570, rs1544410; and RXRA genes: rs10776909, rs10881578, and rs749759 was compared between groups. Results. No significant differences in a frequency distribution of tested polymorphisms were shown between type 2 DM nephropathy patients and controls. A difference was found in IL18 rs360719 polymorphic distribution between the former group and chronic infective tubulointerstitial nephritic patients (Ptrend=0.033, which also differed in this polymorphism from controls (Ptrend=0.005. Conclusion. T-cell cytokine and vitamin D pathway gene polymorphisms are not associated with ESRD due to type 2 DM nephropathy in Polish HD patients. IL18 rs360719 is probably associated with the pathogenesis of chronic infective tubulointerstitial nephritis.

  2. Vascular endothelial growth factor (VEGF-2578А/С gene polymorphism in combination with cytokine gene polymorphisms among patients with rheumatoid arthritis

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    V I Konenkov

    2013-01-01

    Full Text Available Objective: to study the distribution of the genotypes of the vascular endothelial growth factor (VEGF gene and their combinations with those of other cytokines among patients with rheumatoid arthritis (RA and healthy individuals. Subjects and methods. 509 Europeoid women from the eastern regions of Russia, including 374 healthy individuals aged 23-64 years and 135 RA patients aged 27-66 years, were examined. The single nucleotide polymorphism in the promoter region of the genes of VEGC -2578 C/A, tumor necrosis factor-а (TNF-а -863 C/A, TNF-а -308 G/A, TNF-а -238 G/A, and interleukin (IL 1β -31 С/T, IL4 -590 С/T, IL6-174 G/C, IL10-1082 G/A, and IL10-592А/С was studied by restriction fragment length polymorphism analysis. Results. Analysis of the frequency of the genotypes of VEGF in combination with other genotypes has revealed a number of highly significant genetic differences between the groups of healthy individuals and RA patients. Among the combined genetic signs (CGS, whose frequency is significantly increased in RA, there is a predominance of heterozygous CA genotypes at the polymorphic position of VEGF -2578 C/A. Among the CGS positively associated with RA, which include homozygous VEGF -2578 variants, there is a preponderance of AA genotypes whereas all 100% of the homozygous genotypes, whose frequency is significantly decreased in RA, correspond to the variant of СС. The CGS whose frequency is altered in RA along with VEGF genotypes most commonly include the genotypes of IL1ß, IL4, IL10, IL6, and TNF-а. Conclusion. The pathogenesis of RA calls for comprehensive investigation of the role of the angiogenesis and inflammation regulation genes.

  3. DNA Polymorphisms in River Buffalo Leptin Gene

    Directory of Open Access Journals (Sweden)

    B. Moioli

    2010-02-01

    Full Text Available Leptin is a protein involved in the regulation of feed intake, fat metabolism, whole body energy balance, reproduction and hematopoiesis. In cattle Leptin gene has been considered a potential QTL influencing several production traits like meat production, milk performance and reproduction. Several studies on bovine leptin gene have found association between polymorphisms and traits like milk yield, feed intake, fat content, carcass and meat quality. With the aim to assess the presence of sequences polymorphisms in the Buffalo leptin gene, we sequenced the entire coding region and part of the introns on a panel of Italian River Buffalos. In this study we identified a new set of SNP (Single Nucleotide Polymorphism useful for association studies.

  4. Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus by qRT-PCR

    Directory of Open Access Journals (Sweden)

    Iona E. Maher

    2014-03-01

    Full Text Available Investigation of the immune response of the koala (Phascolarctos cinereus is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV, which is of 100% prevalence in northern Australia, has been proposed as an important agent of immune suppression that could explain the koala’s susceptibility to disease. The correct balance of T regulatory, T helper 1 (Th1 and Th2 lymphocyte responses are important to an individual’s susceptibility or resistance to chlamydial infection. The ability to study chlamydial or KoRV pathogenesis, effects of environmental stressors on immunity, and the response of koalas to vaccines under development, by examining the koala’s adaptive response to natural infection or in-vitro stimulation, has been limited to date by a paucity of species- specific reagents. In this study we have used cytokine sequences from four marsupial genomes to identify mRNA sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4, interleukin 6 (IL-6, interleukin 10 (IL-10 and interferon gamma (IFNγ along with CD4 and CD8β. The koala sequences used for primer design showed >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78% with Tasmanian devil amino acid sequences. We report the development of real-time RT-PCR assays to measure the expression of these genes in unstimulated cells and after three common mitogen stimulation protocols (phorbol myristate acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin A. Phorbol myristate acetate/ionomycin was found to be the most effective mitogen to up-regulate the production of IL-4, IL-10 and IFNγ. IL-6 production was not

  5. The role of IL-4 and IL-13 in cutaneous Leishmaniasis.

    Science.gov (United States)

    Hurdayal, Ramona; Brombacher, Frank

    2014-10-01

    Murine models of Leishmania major infection in the 1980s revealed two distinct, counter-regulatory populations of CD4(+) T helper (Th) cells, delineated Th1 and Th2, and their archetypal cytokines, interferon gamma (IFN-γ) and interleukin (IL)-4/IL-13, which promoted resistance/susceptibility to infection, respectively. However, the introduction of global cytokine-deficient mice in the 1990s revealed pleiotropic immune-regulatory mechanisms of IL-4 and IL-13 that either controlled or exacerbated disease. This undermined the basic premise that IL-4/IL-13 played paramount roles in facilitating a non-healing Th2 response to Leishmania infection and instead suggested that both IL-4 and IL-13-dependent and IL-4/IL-13-independent factors orchestrate disease outcome. The recent characterization of cell-type specific IL-4Rα deficient mice was initiated to help reconcile these observations and dissect the cell-specific effects of IL-4/IL-13 during infection. In this review, we summarize original and recent findings with regard to the role of IL-4 and IL-13 in cutaneous Leishmaniasis. Using the information discerned from various studies and our conditional IL-4gene-deficient mice, we particularly discuss the double-edged sword IL-4 (and in some Leishmania disease models IL-13) in driving a susceptible Th2 response, their immune cell targets that support healing or non-healing responses and their novel role in mediating a Th1 response during disease.

  6. Mast cell production and response to IL-4 and IL-13.

    Science.gov (United States)

    McLeod, Jamie J A; Baker, Bianca; Ryan, John J

    2015-09-01

    IL-4 was identified as the first cytokine to be produced by mast cells and is responsible for promoting mast cell IL-13 production. IL-4 and IL-13 play a prominent role in stimulating and maintaining the allergic response. As closely related genes, IL-4 and IL-13 share a common receptor subunit, IL-4Rα, necessary for signaling. Here we summarize the literature on mast cell activation associated with IL-4 and IL-13 production, including downstream signaling. We also describe the positive and negative roles each cytokine plays in mast cell immunity and detail the differences that exist between mouse and human mast cell responses to IL-4 and IL-13.

  7. Cytochrome P450 gene polymorphism and cancer.

    Science.gov (United States)

    Agundez, Jose A G

    2004-06-01

    Human cytochrome P450 (CYP) enzymes play a key role in the metabolism of drugs and environmental chemicals. Several CYP enzymes metabolically activate procarcinogens to genotoxic intermediates. Phenotyping analyses revealed an association between CYP enzyme activity and the risk to develop several forms of cancer. Research carried out in the last decade demonstrated that several CYP enzymes are polymorphic due to single nucleotide polymorphisms, gene duplications and deletions. As genotyping procedures became available for most human CYP, an impressive number of association studies on CYP polymorphisms and cancer risk were conducted. Here we review the findings obtained in these studies regarding CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP8A1 and CYP21 gene polymorphisms. Consistent evidences for association between CYP polymorphisms and lung, head and neck, and liver cancer were reported. Controversial findings suggest that colorectal and prostate cancers may be associated to CYP polymorphisms, whereas no evidences for a relevant association with breast or bladder cancers were reported. We summarize the available information related to the association of CYP polymorphisms with leukaemia, lymphomas and diverse types of cancer that were investigated only for some CYP genes, including brain, esophagus, stomach, pancreas, pituitary, cervical epithelium, melanoma, ovarian, kidney, anal and vulvar cancers. This review discusses on causes of heterogeneity in the proposed associations, controversial findings on cancer risk, and identifies topics that require further investigation. In addition, some recommendations on study design, in order to obtain more conclusive findings in further studies, are provided.

  8. [Cyclooxigenase-1 gene polymorphism and aspirin resistance].

    Science.gov (United States)

    Bondar', T N; Kravchenko, N A

    2012-01-01

    The literature data concerning structure of cyclo-oxigenase-1--the key enzyme in prostaglandin biosynthesis and the main target of anti-platelet therapy with the use of acetylsalicilic acid are presented in the review. The data on cyclooxigenase-1 gene polymorphism, distribution of the revealed variants in various populations and their possible correlation with biochemical and functional aspirin resistance are presented.

  9. Matrix metalloproteinase gene polymorphisms and oral cancer.

    Science.gov (United States)

    Pereira, Andresa C; Dias do Carmo, Elaine; Dias da Silva, Marco A; Blumer Rosa, Luiz E

    2012-12-01

    Since oral squamous cell carcinoma (OSCC) is the most prevalent malignant cancer in the oral cavity, several researches have been performed to study the role of important enzymes in this disease. Among them, the matrix metalloproteinases (MMPs) are highlighted, due to the fact that they are proteinases responsible to degrade many extra-cellular matrix components, making possible the invasion of neoplasic cells. Important tools in cancer prognosis have been utilized aiming to correlate high levels of MMPs and OSCC, such as immunohistochemical, zymographic and mRNA detection methods. However, these techniques are usually applied after cancer detection, characterizing a curative but not a preventive medicine. Trying to make interventions before the development of the disease and making possible the identification of people at high risk and, analysis of modifications in MMP genes has been a chance for modern medicine. Recently, polymorphisms in MMP genes have been related to different neoplasias, including OSCC. Despite investigation is beginning, MMP gene polymorphisms seems to have a promising future in oral cancer research and some of the present results have shown that there are MMP polymorphisms related to an increased risk for developing oral cancer. Key words:Oral cancer, polymorphism, matrix metalloproteinase.

  10. Are "functionally related polymorphisms" of renin-angiotensin-aldosterone system gene polymorphisms associated with hypertension?

    NARCIS (Netherlands)

    Hahntow, I.N.; Mairuhu, G.; Valkengoed, I.G.M.; Koopmans, R.P.; Michel, M.C.

    2010-01-01

    ABSTRACT: BACKGROUND: Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may hav

  11. Autophagy gene polymorphism is associated with susceptibility to leprosy by affecting inflammatory cytokines.

    Science.gov (United States)

    Yang, Degang; Chen, Jia; Shi, Chao; Jing, Zhichun; Song, Ningjing

    2014-04-01

    Autophagy and inflammation closely interact with each other, and together, they play critical roles in bacterial infection. Leprosy is caused by the infection of Mycobacterium leprae (M. leprae). The objective of the study was to investigate the association between polymorphisms in IRGM, an autophagy gene, and susceptibility to leprosy, and identify possible functions of the polymorphism in the infection of M. leprae. Two polymorphisms in IRGM, rs4958842 and rs13361189, were tested in 412 leprosy cases and 432 healthy controls. Levels of inflammatory cytokines including interleukin 1 beta, IL-4, IL-6, and interferon gamma (INF-γ) were measured after the infection of M. leprae in the peripheral blood mononuclear cell (PBMC) of subjects with different genotypes of rs13361189. Data showed that prevalence of rs13361189TC and CC genotypes were significantly higher in leprosy patients than in healthy controls (odds ratio (OR) = 1.49, 95 % confidence interval (CI) 1.09-2.04, P = 0.012; OR = 2.58, 95 % CI 1.65-4.05, P autophagy gene polymorphism was associated with the increased risk of leprosy by affecting inflammatory cytokines.

  12. SH-2-containing protein tyrosine phosphatase 1 is required for IL-4-induced IL-4R expression in spleen cells

    Institute of Scientific and Technical Information of China (English)

    CAO Xin; HUANG Zan; FAN Jingyi

    2005-01-01

    To investigate the role of SH-2-containing protein tyrosine phosphatase 1, SHP-1, in IL-4-induced IL-4 receptor (IL-4R) expression, we examined IL-4 receptor α-chain (IL-4Rα) mRNA expression in Na3VO4-treated wild type (WT) spleen cells and measured IL-4R mRNA in IL-4-stimulated spleen cells of viable motheaten mice (mev/mev). It is found that IL-4-induced IL-4R mRNA expression was impaired in Na3VO4-treated WT spleen cells and IL-4-stimulated mev/mev spleen cells. Here we show that the impaired IL-4-induced IL-4RαmRNA expression was due to reduced expression of IL-4R that led to impaired STAT6 signaling. We further demonstrate that reduction of IL-4Rαprotein expression in mev/mev spleen cells was due to alteration in cell compositions. In mev/mev spleen, the percentages of CD4+, CD8+, and CD19+ cells expressing relatively high levels of IL-4R were reduced dramatically while the percentages of Mac-1+ and Gr-1+ cells with relative low levels of IL-4R increased greatly. Despite the profound effect of reduced expression of IL-4R protein, the IL-4RαmRNA expression was comparable in spleen cells of littermate control mice (+/() and mev/mev mice and no differences were found in B cells, T cells, and macrophages, suggesting cell type-specific downregulation of IL-4R expression in macrophages through a posttranscriptional mechanism. Our study suggests that SHP-1 is required for IL-4-meidated function and indirectly regulates IL-4-meidated function in spleen cells by affecting hematopoiesis.

  13. Oligonucleotide fishing for STAT6: cross-talk between IL-4 and chemokines

    DEFF Research Database (Denmark)

    Eriksen, K W; Nielsen, M; Kaltoft, K

    2001-01-01

    Signal transducer and activator of transcription 6 (STAT6) is essential for the biological activities of interleukin-4 (IL-4) and the development of allergic responses in mice. Here we report on a sensitive and specific assay for STAT6 activation in response to IL-4. We took advantage of double-stranded...... oligonucleotide probes containing a STAT6-binding gene-sequence from the promotor of the immunoglobulin heavy chain germline epsilon transcript to study the IL-4-induced DNA binding of STAT6. Using these probes, we show that repeated adjacent STAT6-binding sites result in enhanced STAT6-DNA binding. Moreover......, the distance between the binding sites is critical for STAT-DNA binding, i.e. STAT6 binding is decreased at distances above 20 nucleotides between neighbouring binding sites. Using this assay to study cross-talk between IL-4 and chemokines, we provide evidence that MIP-1beta and MIG inhibit IL-4-induced STAT6...

  14. Association of ADAM33 gene polymorphisms with allergic asthma

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zand Karimi

    2014-09-01

    Conclusion: Polymorphisms of ADAM33 gene might be associated with severe asthma and sensitivity to aeroallergens in northeast of Iran, but further studies are needed to determine the polymorphisms in this area and other regions of our country.

  15. Association of Reelin gene polymorphisms with autism.

    Science.gov (United States)

    Serajee, Fatema J; Zhong, Hailang; Mahbubul Huq, A H M

    2006-01-01

    Genome scans indicate a linkage of autism to the chromosome 7q21-q36 region. Recent studies suggest that the Reelin gene may be one of the loci contributing to the positive linkage between chromosome 7q and autism. However, these studies were relatively small scale, using a few markers in the gene. We investigated 34 single nucleotide polymorphisms (SNPs) in the Reelin gene with an average spacing between the SNPs of 15 kb for evidence of association with autism. There were significant differences in the transmission of the alleles of exon 22 and intron 59 SNP to autistic subjects. Our findings support a role for the Reelin gene in the susceptibility to autism.

  16. DNA Methyltransferase 3B Gene Promoter and Interleukin-1 Receptor Antagonist Polymorphisms in Childhood Immune Thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Margarita Pesmatzoglou

    2012-01-01

    Full Text Available Primary immune thrombocytopenia (ITP is one of the most common blood diseases as well as the commonest acquired bleeding disorder in childhood. Although the etiology of ITP is unclear, in the pathogenesis of the disease, both environmental and genetic factors including polymorphisms of TNF-a, IL-10, and IL-4 genes have been suggested to be involved. In this study, we investigated the rs2424913 single-nucleotide polymorphism (SNP (C46359T in DNA methyltransferase 3B (DNMT3B gene promoter and the VNTR polymorphism of IL-1 receptor antagonist (IL-1 Ra intron-2 in 32 children (17 boys with the diagnosis of ITP and 64 healthy individuals. No significant differences were found in the genotype distribution of DNMT3B polymorphism between the children with ITP and the control group, whereas the frequency of allele T appeared significantly increased in children with ITP (P = 0.03, OR = 2, 95% CI: 1.06–3.94. In case of IL-1 Ra polymorphism, children with ITP had a significantly higher frequency of genotype I/II, compared to control group (P = 0.043, OR = 2.60, 95% CI: 1.02–6.50. Moreover, genotype I/I as well as allele I was overrepresented in the control group, suggesting that allele I may have a decreased risk for development of ITP. Our findings suggest that rs2424913 DNMT3B SNP as well as IL-1 Ra VNTR polymorphism may contribute to the susceptibility to ITP.

  17. Androgen receptor gene polymorphism in zebra species

    Directory of Open Access Journals (Sweden)

    Hideyuki Ito

    2015-09-01

    Full Text Available Androgen receptor genes (AR have been found to have associations with reproductive development, behavioral traits, and disorders in humans. However, the influence of similar genetic effects on the behavior of other animals is scarce. We examined the loci AR glutamine repeat (ARQ in 44 Grevy's zebras, 23 plains zebras, and three mountain zebras, and compared them with those of domesticated horses. We observed polymorphism among zebra species and between zebra and horse. As androgens such as testosterone influence aggressiveness, AR polymorphism among equid species may be associated with differences in levels of aggression and tameness. Our findings indicate that it would be useful to conduct further studies focusing on the potential association between AR and personality traits, and to understand domestication of equid species.

  18. Single nucleotide polymorphisms (SNPs) in key cytokines may modulate food allergy phenotypes

    Science.gov (United States)

    Brown, Paula; Nair, Bindukumar; Sykes, Donald E.; Rich, Gary; Reynolds, Jessica L.; Aalinkeel, Ravikumar; Wheeler, John; Schwartz, Stanley A.

    2012-01-01

    Single nucleotide polymorphisms (SNPs) can play a direct or indirect role in phenotypic expression in food allergy pathogenesis. Our goal was to quantitate the expression of SNPs in relevant cytokines that were expressed in food allergic patients. SNPs in cytokine genes IL-4 and IL-10 are known to be important in IgE generation and regulation. We examined IL-4 (C-590T), IL-4Rα (1652A/G) and IL-10 (C-627A) SNPs using real-time PCR followed by restriction fragment length polymorphism (RFLP) analysis. Our results show that the AA, AG and GG genotypes for IL-4Rα (1652A/G) polymorphisms were statistically different in radioallergosorbent test (RAST) positive versus negative patients, and although no statistically significant differences were observed between genotypes in the IL-4 (C-590T) and IL-10 (C-627A) SNPs, we observed a significant decrease in IL-4 (C-590T) gene expression and increase in IL-4Rα (1652A/G) and IL-10 (C-627A) gene expression between RAST+ versus RAST− patients, respectively. We also observed significant modulation in the protein expression of IL-4 and IL-10 in the serum samples of the RAST+ patients as compared to the RAST− patients indicating that changes in SNP expression resulted in altered phenotypic response in these patients. PMID:23230389

  19. 内耳注入携带 IL -4基因的骨髓间充质干细胞对豚鼠免疫性内耳病基因治疗的研究%Gene Therapy of Inner Ear Injection with Bone -Marrow Mesenchymal Stem Cells Decorated with Interleukin-4 Gene on Immune-Mediated Inner Ear Disease in Guinea Pigs

    Institute of Scientific and Technical Information of China (English)

    郭浪; 谭长强; 刘树森; 江萍; 衡伟伟

    2014-01-01

    目的:研究内耳局部植入白细胞介素4(IL -4)基因修饰骨髓间充质干细胞(bone-marrow mesen-chymal stem cells ,BMSCs)对免疫性内耳病豚鼠内耳病理损伤和听功能的调节与治疗作用。方法采用钥孔嘁血蓝蛋白(KLH)抗原在已致敏的豚鼠圆窗龛局部免疫,制成豚鼠免疫性内耳病模型55只,分为五组:A组(BMSCs载体组)、B组(BM SCs空载体对照组)、C组(重组慢病毒IL -4基因组)、D组(慢病毒空载体对照组)及E组(模拟手术对照组),每组11只,各组均将相应的悬液20μl[BMSCs悬液中含BMSCs(1.5~2.0)×106,慢病毒浓缩液浓度为0.5×108 pfu]经鼓阶开窗植入内耳。采用免疫荧光组织化学试验法、免疫酶组织化学试验法观察IL -4基因产物在内耳组织结构中的分布和表达情况,酶联免疫吸附试验观察血清抗KLH特异性抗体水平,ABR测试听功能变化。结果与免疫前相比,免疫后A、B、C组ABR波Ⅲ阈值不同程度降低,A组阈值降低更明显,差异有统计学意义(P<0.05);免疫组织化学染色显示BMSCs荧光反应阳性细胞主要分布在鼓阶、前庭阶;内耳光镜观察A、B、C组仅在鼓阶内有絮状物,注射部位有少量红细胞和白细胞,D、E组可见不同程度的膜迷路积水,螺旋神经节和蜗轴小血管周围有单个核细胞浸润。结论重组IL -4基因的慢病毒载体可在体外成功转染BM SCs ,经鼓阶途径植入内耳后可在内耳迁移并产生基因产物IL -4,可明显减轻免疫性内耳病动物的内耳免疫炎性反应和听功能损伤,而BMSCs可以作为细胞载体把携带有目的基因的治疗因子迁移到损伤部位而发挥治疗作用。%Objective To evaluate the gene therapeutic effects of guinea pigs model with immune -mediated inner ear disease(IMIED)after locally injection of bone -marrow mesenchymal stem cells(BMSCs) decorated by in

  20. Identification of Rabbit Myostatin Gene Polymorphisms

    Directory of Open Access Journals (Sweden)

    T. I. Amalianingsih

    2015-08-01

    Full Text Available The existence of selection on the rabbits with potential for meat has only been seen from phenotypic aspects including performance and productivity, while the molecular genetic studies are still very rare. One of the candidate genes for meat production traits in rabbit is myostatin. Totally 50 blood samples of male rabbits from Rex, Satin, Reza (crossing from Rex and Satin, Flemish Giant and FZ3 (crossing from Flemish Giant and Reza breed were used at Indonesian Research Institute for Animal Production (IRIAP. Genetic polymorphism by Polymerase Chain Reaction – Restriction Fragment Length Polymorphism (PCR-RFLP method used FspBI restriction enzyme. PCR-RFLP data were analyzed by calculating allele and genotype frequencies. Sequencing was performed in rabbit with different genotypes which represents each of the samples. Genotype of AT had two cut points of the FspBI restriction enzyme at the base position of 508 bp and 444 bp. The cut point at the base position of 446 bp was site mutation base T became A. Genotype of TT had one cut point at the base position of 508 bp and no mutation site. Allele T had higher frequency than allele A and just Rex and Reza rabbit breeds had two alleles. The other rabbits (Satin, Flemish Giant and FZ3 only had one allele i.e., allele T. PCR - RFLP analysis of the MSTN|FspBI gene segments was polymorphic in Rex and Reza rabbit breeds. All of rabbit breeds in this study did not have AA genotype.

  1. Critical role of p38 MAPK in IL-4-induced alternative activation of peritoneal macrophages.

    Science.gov (United States)

    Jiménez-Garcia, Lidia; Herránz, Sandra; Luque, Alfonso; Hortelano, Sonsoles

    2015-01-01

    Alternative activation of macrophages plays an important role in a range of physiological and pathological processes. This alternative phenotype, also known as M2 macrophages, is induced by type 2 cytokines such as IL-4. The binding of IL-4 to its receptor leads to activation of two major signaling pathways: STAT-6 and PI3K. However, recent studies have described that p38 MAPK might play a role in IL-4-dependent signaling in some cells, although its role in macrophages is still controversial. In this study, we investigated whether p38 MAPK plays a role in the polarization of macrophages in mice. Our results reveal that IL-4 induces phosphorylation of p38 MAPK in thioglycollate-elicited murine peritoneal macrophages, in addition to STAT-6 and PI3K activation. Furthermore, p38 MAPK inactivation, by gene silencing or pharmacological inhibition, suppressed IL-4-induced typical M2 markers, indicating the involvement of p38 MAPK in the signaling of IL-4 leading to M2-macrophage polarization. Moreover, p38 MAPK inhibition blocked phosphorylation of STAT-6 and Akt, suggesting that p38 MAPK is upstream of these signaling pathways. Finally, we show that in an in vivo model of chitin-induced M2 polarization, p38 MAPK inhibition also diminished activation of M2 markers. Taken together, our data establish a new role for p38 MAPK during IL-4-induced alternative activation of macrophages. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Polymorphism of starch pathway genes in cassava.

    Science.gov (United States)

    Vasconcelos, L M; Brito, A C; Carmo, C D; Oliveira, E J

    2016-12-02

    The distribution and frequency of single nucleotide polymorphisms (SNPs) can help to understand changes associated with characteristics of interest. We aimed to evaluate nucleotide diversity in six genes involved in starch biosynthesis in cassava using a panel of 96 unrelated accessions. The genes were sequenced, aligned, and used to obtain values for nucleotide diversity (π), segregating sites (θ), Tajima's D test, and neighbor-joining (NJ) clustering. On average, one SNP per 147 and 171 bp was identified in exon and intron regions, respectively. Thirteen heterozygous loci were found. Three of seven SNPs in the exon region resulted in non-synonymous replacement or four synonymous substitutions. However, no associations were noted between SNPs and root dry-matter content. The parameter π ranged from 0.0001 (granule bound starch synthase I) to 0.0033 (α-amylase), averaging 0.0011, while θ ranged from 0.00014 (starch branching enzyme) to 0.00584 (starch synthase I), averaging 0.002353. The θ diversity value was typically double that of the π. Results of the D test did not suggest any evidence of deviance of neutrality in these genes. Among the evaluated accession, 82/96 were clustered using the NJ method but without a clear separation of the root dry-matter content, root pulp coloration, and classification of the cyanogenic compound content. High variation in genes of the starch biosynthetic pathway can be used to identify associations with the functional properties of starch for the use of polymorphisms for selection purposes.

  3. Detection of allergenic compounds using an IL-4/luciferase/CNS-1 transgenic mice model.

    Science.gov (United States)

    Bae, Chang Joon; Lee, Jae Won; Bae, Hee Sook; Shim, Sun Bo; Jee, Seung Wan; Lee, Su Hae; Lee, Chang Kyu; Hong, Jin Tae; Hwang, Dae Youn

    2011-04-01

    The interleukin-4 (IL-4) signaling cascade has been identified as a potentially important pathway in the development of allergies. The principal objective of this study was to produce novel transgenic (Tg) mice harboring the luciferase gene under the control of the human IL-4 promoter and the enhancer of IL-4 (CNS-1), in an effort to evaluate three types of allergens including a respiratory sensitizer, vaccine additives, and crude extracts of natural allergens in vivo. A new lineage of Tg mice was generated by the microinjection of pIL-4/Luc/CNS-1 constructs into a fertilized mice egg. The luciferase activity was successfully regulated by the IL-4 promoter in splenocytes cultured from IL-4/Luc/CNS-1 Tg mice. From the first five founder lines, one (#57) evidencing a profound response to ovalbumin was selected for use in evaluating the allergens. Additionally, the lungs, thymus, and lymph nodes of IL-4/Luc/CNS-1 Tg mice evidenced high luciferase activity in response to allergens such as phthalic anhydride (PA), trimellitic anhydride, ovalbumin, gelatin, Dermatophagoides pteronyssinus extracts, and Japanese cedar pollen, whereas key allergy-related indicators including ear thickness, Immunoglobulin E concentration, and the infiltration of inflammatory leukocytes in response to PA were unaltered in the Tg mice relative to the non-Tg mice. Furthermore, the expression levels of endogenous type 2 helper T cells cytokines and proinflammatory cytokines were similarly increased in these organs of IL-4/Luc/CNS-1 Tg mice in response to allergens. These results indicate that IL-4/Luc/CNS-1 Tg mice may be used as an animal model for the evaluation and prediction of the human body response to a variety of allergens originating from the environment and from certain industrial products.

  4. APOE gene polymorphism analysis in Barranquilla, Colombia.

    Science.gov (United States)

    Ruiz, Martha; Arias, Isis; Rolón, Gloria; Hernández, Enio; Garavito, Pilar; Silvera-Redondo, Carlos

    2016-03-03

    The genetic variability present in the APOE gene polymorphism is considered an important factor associated with predisposition to diseases affecting lipid metabolism, as well as heart diseases and Alzheimer's disease, among others. Understanding it as a risk factor in different populations and ethnic groups is a useful tool.  To analyze the APOE gene polymorphism and determine allelic and genotypic frequencies of a representative sample of population from Barranquilla, Colombia.  We performed a descriptive and comparative study. The sample size was 227 unrelated individuals from Barranquilla, Colombia.  The most frequent allele was the ε3, with 85%, followed by the ε4 allele (13%) and ε2 (1.8%). The genotypes found were: ε3/ε3: 71.8%, ε3/ε4: 24.2%, ε2/ε3: 2.2%, ε2/ε4: 1.3% and ε4/ε4: 0.4%. The ε2/ε2 genotype was not found in this study. The sample exhibited the Hardy-Weinberg equilibrium.  The frequency of the ε3 allele and the ε3/ε3 genotype was similar to that reported in the literature in countries like Brazil, Mexico, Colombia, and in some Colombian Amerindian ethnic groups. The ε2/ε2 genotype was absent. This result is consistent with those found in other population groups worldwide. The frequency of the ε4 allele and the genotypes associated in this population could be related to the presence of diseases such as hypercholesterolemia, myocardial infarction and Alzheimer.

  5. INTERLEUKIN 1 AND INTERLEUKIN 4 GENES POLYMORPHISM ASSOCIATED WITH EARLY AND PRESCHOOL AGE CHILDREN SENSITIZATION TO STREPTOCOCCUS PYOGENES

    Directory of Open Access Journals (Sweden)

    A. V. Shabaldin

    2016-01-01

    Full Text Available Background. Streptococcus pyogenes infection and sensitization to its antigens is considered to be an unfavorable factor for the induction of rheumatic pathology. The search for genetic predictors of rheumatic diseases in general, and sensitization to S. pyogenes, in particular, is of high relevance in modern medicine.Objective. To study the associations between interleukin 1 and interleukin 4 gene polymorphisms and the development of sensitization to antigens of S. pyogenes in toddlers and preschool children.Materials and methods. 771 children aged 2–6 years with recurrent acute respiratory tract infections treated by allergist-immunologist and otorhinolaryngologist were included in the study. Antibodies against S. pyogenes were determined by ELISA using commercial kits “Immunoteks” (Stavropol, Russia in all children. Children with IgG immune response to S. pyogenes were assigned to the study group (n = 306, whereas children without this response were assigned to the control group (n = 465. Both groups underwent gene typing of IL1B (+3953, C→T, rs 114634, IL1Ra (VNTR, intron 2, 89 bp and IL4 (VNTR intron 3, 70 bp gene polymorphisms in the Laboratory for Pharmacogenomics, ICBFM SB RAS. The data were processed using routine statistical methods for genetic analysis and the statistical software package Statistica 6.0. There were no deviations from Hardy–Weinberg equilibrium across all loci, suggesting validity of association studies between individual and combined genotypes and sensitization to antigens of S. pyogenes.Results. Positive association between sensitization to antigens of S. pyogenes and individual genotypes have been found: IL1B (+3953, C→T*C,T (52.6% in the study group vs. 39.8% in the control group, p = 0.001; OR = 2.02; CI(99% 0.47–5.93, IL1Ra (VNTR, intron 2, 89 bp*2r,5r (7.19% in the study group vs. 1.29% in the control group, p = 0.001; OR = 5.59; CI(99% 1.58–19.77, IL4 (VNTR intron 3, 70 bp*2r,2r (6

  6. Association study of interleukin-4 polymorphisms with paranoid schizophrenia in the Polish population: a critical approach.

    Science.gov (United States)

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

    2012-08-01

    Changes in immunological system are one of dysfunctions reported in schizophrenia. Some changes based on an imbalance between Th1 and Th2 cytokines results from cytokine gene polymorphisms. Interleukin-4 gene (IL4) is considered as a potential candidate gene in schizophrenia association studies. The aim of the current case-control study was to examine whether the -590C/T (rs2243250) and -33C/T (rs2070874) IL4 gene polymorphisms are implicated in paranoid schizophrenia development in the Polish population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. The genotypes and alleles distribution of both SNPs were analysed in patients (n = 182) and healthy individuals constituted the control group (n = 215). The connection between some clinical variables and studied polymorphisms has been examined as well. We did not revealed any association between the -590C/T and -33C/T polymorphisms and paranoid schizophrenia. In case of both SNPs the homozygous TT genotype was extremely rare. Both polymorphic sites of the IL4 gene were found to be in a very strong linkage disequilibrium. However we did not identify a haplotype predispose to paranoid schizophrenia. No associations were also observed between the clinical course and psychopathology of the disease and the genotypes of both analysed polymorphisms. Our results suggest that the polymorphisms -590C/T in IL4 gene promoter region and -33C/T in the 5'-UTR are not involved in the pathophysiology of paranoid schizophrenia in Polish residents.

  7. H pylori seropositivity and cytokine gene polymorphisms

    Institute of Scientific and Technical Information of China (English)

    Yasuaki Saijo; Eiji Yoshioka; Tomonori Fukui; Mariko Kawaharada; Fumihiro Sata; Hirokazu Sato; Reiko Kishi

    2007-01-01

    AIM: To investigate whether the pro- and antiinflammatory cytokine gene polymorphisms, IL1B-511C/T,IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori.METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C,TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5'nuclease assay.RESULTS: In gender- and age-adjusted logistic analyses,the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95% CI: 0.03-0.59, P = 0.007).After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C;OR = 0.30, 95% CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95% CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95% CI, P =0.042: 1.04-6.47; C/C: OR = 3.17, 95% CI: 1.23-8.14,P = 0.017). Among current smokers, the subjects with IL6-634C/G had a significantly higher OR (reference C/C;OR = 2.28, 95% CI: 1.13-4.58, P = 0.021). However,the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant.CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine

  8. Association between cytokine gene polymorphisms and outcome of hepatitis B virus infection in southern Brazil.

    Science.gov (United States)

    Gusatti, Carolina de Souza; Costi, Cintia; de Medeiros, Rúbia Marília; Halon, Maria Laura; Grandi, Tarciana; Medeiros, Arlete Ferrari Rech; da Silva, Cláudia Maria Dornelles; Rodenbusch, Rodrigo; Silva, Márcia Susana Nunes; Niel, Christian; Rossetti, Maria Lucia Rosa

    2016-10-01

    A number of studies have demonstrated associations between cytokine gene polymorphisms and outcome of hepatitis B virus (HBV) infection. However, no general consensus has been reached, possibly due to differences between ethnic groups. In this study, 345 individuals living in southern Brazil, including 196 chronic HBV carriers and 149 subjects who had spontaneously recovered from acute infection, were enrolled to evaluate the influence of cytokine gene polymorphisms on the outcome of HBV infection. Most participants were of European descent. Genotyping of IL2-330 G/T, IL4-589C/T, IL6-174 G/C, IL10-592C/A, IL10-1082 A/G, IL17A-197 G/A, IL17A-692 T/C, TNF-α-238 G/A, and TNF-α-308 G/A single nucleotide polymorphisms was performed by using the minisequencing (single base extension) method. By multivariable analysis, a statistically significant association was found between genotypic profile AA + GA in TNF-α-308 and chronic HBV infection (OR, 1.82; 95%CI, 1.01-3.27; P = 0.046). In southern Brazil, the carriers of the -308A allele in the TNF-α gene promoter have a moderately higher risk of becoming chronic carriers in case of HBV infection. In addition, patients with chronic active hepatitis B (n = 60) exhibited a decreased frequency (3.3%) of the TNF-238A allele when compared to that (14.8%) found among asymptomatic HBV carriers (n = 136), suggesting that this could be a protective factor against liver injury (OR, 0.17; 95%CI, 0.04-0.076; P = 0.023). J. Med. Virol. 88:1759-1766, 2016. © 2016 Wiley Periodicals, Inc.

  9. Prothrombotic Gene Polymorphisms in Young Patients with Cerebrovascular Accident

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    Kuyaþ Hekimler Öztürk

    2013-07-01

    Full Text Available Aim: Cerebrovascular diseases are complex multifactorial disorders showing an increased incidence with increasing age and affected by genetic and environmental factors. Although risk factors for cerebrovascular diseases include age, sex, lineage, hypertension, diabetes mellitus, hypercholesterolemia; in young cerebrovascular patients below age 45, genetic factors may also contribute to the etiology. In this retrospective study, prothrombotic gene polymorphisms which are thought to be related with formation of disease in young adults with cerebrovascular accident (CVA were investigated. Material and Method: In the current study, Methylenetetrahydropholate Reductase (MTHFR C677T and A129C; Prothrombin (Factor II G20210A; Factor V Leiden G1691A prothrombotic gene polymorphisms were evaluated for 43 young patients under the age of 45 with cerebrovascular accident history. Result: For 43 young patients with cerebrovascular incident history, the frequency of following polymorphisms were determined as follows; MTHFR C677T polymorphism heterozygous frequency is 46.1%, homozygous frequency is 9.3%; MTHFR A1298C polymorphism heterozygous frequency is 39.47%, homozygous frequency is 26.31%; Prothrombin polymorphism heterozygous and homozygous frequency is 2.3%; FactorV Leiden polymorphism heterozygous frequency is 9.3%. Discussion: After evaluation the experimental results, we believe that MTHFR gene C677T and A1298C polymorphisms might be risk factors in CVAs. It was observed that cigarette usage, hypertension and existence of family story in addition to these polymorphisms increase the available risk.

  10. Strategies targeting the IL-4/IL-13 axes in disease.

    Science.gov (United States)

    May, Richard D; Fung, Michael

    2015-09-01

    IL-4 and IL-13 are pleiotropic Th2 cytokines produced by a wide variety of different cell types and responsible for a broad range of biology and functions. Physiologically, Th2 cytokines are known to mediate host defense against parasites but they can also trigger disease if their activities are dysregulated. In this review we discuss the rationale for targeting the IL-4/IL-13 axes in asthma, atopic dermatitis, allergic rhinitis, COPD, cancer, inflammatory bowel disease, autoimmune disease and fibrotic disease as well as evaluating the associated clinical data derived from blocking IL-4, IL-13 or IL-4 and IL-13 together.

  11. Commentary: IL-4 and IL-13 receptors and signaling.

    Science.gov (United States)

    McCormick, Sarah M; Heller, Nicola M

    2015-09-01

    Interleukin (IL)-4 and IL-13 were discovered approximately 30years ago and were immediately linked to allergy and atopic diseases. Since then, new roles for IL-4 and IL-13 and their receptors in normal gestation, fetal development and neurological function and in the pathogenesis of cancer and fibrosis have been appreciated. Studying IL-4/-13 and their receptors has revealed important clues about cytokine biology and led to the development of numerous experimental therapeutics. Here we aim to highlight new discoveries and consolidate concepts in the field of IL-4 and IL-13 structure, receptor regulation, signaling and experimental therapeutics.

  12. Anti- and proinflammatory cytokine gene polymorphism and genetic predisposition: association with smoking, tumor stage and grade, and bacillus Calmette-Guérin immunotherapy in bladder cancer.

    Science.gov (United States)

    Ahirwar, Dinesh; Kesarwani, Pravin; Manchanda, Parmeet Kaur; Mandhani, Anil; Mittal, Rama Devi

    2008-07-01

    Cytokines mediate many immune and inflammatory responses contributing to tumorigenesis. The present study evaluated polymorphisms of IL4, IL6, and TNF (previously TNFA) genes influencing risk in development of transitional cell carcinoma of bladder and recurrence after bacillus Calmette-Guérin (BCG) immunotherapy. The study included 136 unrelated histopathologically confirmed cases and 200 population-based controls. Genomic DNA was extracted from peripheral leukocytes and genotyped for polymorphism in IL4 intron 3, with point mutations identified by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) in IL6-174 G/C and by PCR-restriction fragment length polymorphism analysis in TNF-308 G/A. The IL6 variant C/C exhibited significant association with bladder cancer risk (odds ratio OR = 2.811, P = 0.004), but IL4 and TNF genetic variants did not. Significant association was observed for IL4 (B1/B2+B2/B2) with high-grade or late-stage tumor for TaG3+T1 and T2+ (OR = 5.950, and 6.342 respectively) and with smoking (P = 0.004, OR = 4.202). Low recurrence risk was observed in BCG-treated patients carrying C/C genotype of IL6 (hazard ratio = 0.298, P = 0.03), and also higher recurrence-free survival (log rank P = 0.021). TNF and IL4 demonstrated no association of bladder cancer risk and BCG therapy. The low-producing variant C/C of IL6 may be a risk factor for bladder cancer, whereas high-producing genotypes of IL4 (B1/B2+B2/B2) may predispose to higher risk in patients with high-grade or late-stage tumor and smoking habits. The low-producing C/C IL6 genotype, which favors Th1 response, may be a beneficial prognostic indicator for treatment and survival of BCG-treated patients.

  13. IL4 — EDRN Public Portal

    Science.gov (United States)

    From NCBI Gene: The protein encoded by this gene is a pleiotropic cytokine produced by activated T cells. This cytokine is a ligand for interleukin 4 receptor. The interleukin 4 receptor also binds to IL13, which may contribute to many overlapping functions of this cytokine and IL13. STAT6, a signal transducer and activator of transcription, has been shown to play a central role in mediating the immune regulatory signal of this cytokine. This gene, IL3, IL5, IL13, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL13. This gene, IL13 and IL5 are found to be regulated coordinately by several long-range regulatory elements in an over 120 kilobase range on the chromosome. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008

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

    African Journals Online (AJOL)

    Pramudji Hastuti

    2016-01-11

    Jan 11, 2016 ... Obesity is caused by an imbalance between food intake and energy expenditure. The etiology of ... ried out under The Code of Ethics of the World Medical Asso- ..... polymorphisms in obese Mexican subjects. Am J Agric Biol ... Synergistic effect of LEP and LEPR gene polymorphism on body · mass index in ...

  15. Polymorphisms in autophagy genes and susceptibility to tuberculosis.

    Directory of Open Access Journals (Sweden)

    Mario Songane

    Full Text Available Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M. tuberculosis genotypes, as determined by spoligotyping. The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers. No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between polymorphisms in LAMP1 (p = 0.02 and MTOR (p = 0.02 and infection with the successful M. tuberculosis Beijing genotype. The polymorphisms examined were not associated with M. tuberculosis induced cytokines, except for a polymorphism in ATG10, which was linked with IL-8 production (p = 0.04. All associations found lost statistical significance after correction for multiple testing. This first examination of a broad set of polymorphisms in autophagy genes fails to show a clear association with TB, with M. tuberculosis Beijing genotype infection or with ex-vivo pro-inflammatory cytokine production.

  16. Association between Tryptophan Hydroxylase 2 Gene Polymorphism and Completed Suicide

    Science.gov (United States)

    Fudalej, Sylwia; Ilgen, Mark; Fudalej, Marcin; Kostrzewa, Grazyna; Barry, Kristen; Wojnar, Marcin; Krajewski, Pawel; Blow, Frederic; Ploski, Rafal

    2010-01-01

    The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…

  17. MOLECULAR GENETIC ANALYSIS OF INTERLEUKIN 4 GENE POLYMORPHISM AMONG TELEUTIANS, SHORIANS, AND CAUCASIANS IN KEMEROVO REGION

    Directory of Open Access Journals (Sweden)

    A. V. Ostaptseva

    2006-01-01

    Full Text Available Abstract. An interleukin 4 polymorphism has been studied in Teleutians, Shorians, and Caucasoids living in the Kemerovo Region. The groups of Teleutians and Caucasoids are characterised with even or close-to-even distribution of the IL-4 alleles. The most widespread genotype in populations of Teleutians and Caucasoids was the 2R/3R heterozygosity, and 3R/3R proved to be the mostly rare. These data are indicative for mixing processes among Teleutians in the Kemerovo Region and Siberian Caucasoids. The major IL-4 genotype in Shorian population was 3R/3R, and the heterozygotic genotype 2R/3R took the second position.

  18. Relationship between cytokines gene polymorphism and susceptibility to hepatitis B virus intrauterine infection

    Institute of Scientific and Technical Information of China (English)

    ZHU Qi-rong; GE Yan-ling; GU Shao-qing; YU Hui; WANG Jian-she; GU Xin-huan; FEI Lin-e; DONG Zuo-quan

    2005-01-01

    Background The influences of genomic background are confirmed in more diseases. Immunologic tolerance after intrauterine infection of hepatitis B virus is considered to occur in T cells. Cytokines work effectively in eliminating virus by immune system after hepatitis B virus infection. To explore the relationship between cytokines (tumor necrosis factor-α, interferon-γ, interleukin-4 and interleukin-10), which expressed abnormal quantity in the peripheral blood to intrauterine hepatitis B virus infectious children, gene single nucleotide polymorphism (SNP) and susceptibility to hepatitis B virus intrauterine infection. Methods This is a cross sectional study of molecular clinical epidemiology. The subjects in this study were selected from outpatients of hepatitis B vaccine follow-up special clinics of our hospital in the period. According to intrant criteria, the high risk children of hepatitis B virus (HBV) intrauterine infection were divided into immune failure group (group Ⅰ); and immune effective group (group Ⅱ) and non high risk children belonged to the control group. Four gene SNP sites of TNF-α -238, IFN-γ +874, IL-4 -590 and IL-10 -1082 were determined by real-time quantitative fluorescent polymerase chain reaction (PCR). Results The significant differences of TNF-α -238 A allele frequency were found between group Ⅰ and groupⅡ (χ2=6.797,P0.05); the significant differences of IFN-γ +874 A allele frequency were found between groupⅠ and groupⅡ(χ2=7.238,P0.05); the significant differences of IL-4 -590 C/T allele frequency were not found between groupⅠand group Ⅱ(χ2=0.632,P>0.05), also groupⅠ and the control group (χ2=0.584,P>0.05), and the groupⅡ and the control group (χ2=0.004,P>0.05)respectively; The significant differences of IL-10 -1082 G allele frequency were found between groupⅡ and groupⅠ (χ2=10.359,P0.05). Conclusions This study suggested the possibility that the TNF-α -238 A allele and IFN-γ +874 A allele were

  19. IL-4 and IL-4 receptor expression is dispensable for the development and function of natural killer T cells.

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    Archna Sharma

    Full Text Available CD4 T cells acquire functional properties including cytokine production upon antigenic stimulation through the T cell receptor (TCR and differentiate into T helper (Th cells. Th1 cells produce interferon (IFN-γ and Th2 cells produce interleukin (IL-4. Th1 and 2 cells utilize IFN-γ and IL-4 for further maturation and maintenance, respectively. Promyelocytic leukemia zinc finger (PLZF-expressing invariant natural killer T (iNKT cells develop in the thymus and acquire functional ability to produce IL-4 and IFN-γ in the thymus in the absence of antigenic stimulation. In response to antigenic stimulation, iNKT cells rapidly produce IFN-γ and IL-4. However, it is still unknown as to whether iNKT cells require these cytokines for maturation or survival in vivo. In this study, using IL-4- and IL-4 receptor- (IL-4R deficient mice, we demonstrate that IL-4 as well as IL-4R expression is dispensable for the development, function and maintenance of iNKT cells.

  20. Impact of lipoprotein lipase gene polymorphisms on ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Toshihito Kosaka; Taizou Shiraishi; Masatoshi Watanabe; Takayuki Yamamoto; Ai Nakahara; Takahiko Katoh; Junji Yoshino; Kazuo Inui; Takao Wakabayashi; Kazumu Okushima; Takashi Kobayashi; Hironao Miyoshi; Yuta Nakamura; Shigekazu Hayashi

    2006-01-01

    AIM: To examine the influence of lipoprotein lipase (LPL)gene polymorphism in ulcerative colitis (UC) patients.METHODS: Peripheral blood was obtained from 131 patients with UC and 106 healthy controls for DNA extraction. We determined LPL gene polymorphisms affecting the enzyme at Ser447stop, as well as Hind Ⅲ and Pvu Ⅱ polymorphisms using PCR techniques. PCR products were characterized by PCR-RFLP and direct sequencing.Polymorphisms were examined for association with clinical features in UC patients. Genotype frequencies for LPL polymorphisms were also compared between UC patients and controls.RESULTS: In patients with onset at age 20 years or younger, C/G and G/G genotypes for Ser447stop polymorphism were more prevalent than C/C genotype (OR= 3.13, 95% CI = 0.95-10.33). Patients with H+/- or H-/-genotype for HindⅢ polymorphism also were more numerous than those with H+/+ genotype (OR = 2.51, 95%CI = 0.85-7.45). In the group with H+/+ genotype for HindⅢ polymorphism, more patients had serum triglyceride concentrations over 150 mg/dL than patients with H+/- or H-/- genotype (P < 0.01, OR = 6.46, 95% CI =1.39-30.12). Hypertriglycemia was also more prevalent in patients with P+/+ genotypes for Pvu Ⅱ polymorphism (P< 0.05, OR = 3.0, 95% CI = 1.06-8.50). Genotype frequency for LPL polymorphism did not differ significantly between UC patients and controls.CONCLUSION: Ser447stop and HindⅢ LPL polymorphisms may influence age of onset of UC, while HindⅢand PvuⅡ polymorphisms influence serum triglyceride in UC patients.

  1. Association between non-atopic hand eczema and interleukin-13 gene polymorphism in Taiwanese nursing population.

    Science.gov (United States)

    Chen, Yin-Chun; Tu, Hung-Pin; Wu, Ching-Shuang; Ko, Ying-Chin; Yu, Hsin-Su; Lu, Yi-Wei; Li, Wan-Chen; Chen, Gwo-Shing; Lan, Cheng-Che E

    2012-12-01

    Chronic hand eczema is an important occupational skin disease with atopic dermatitis (AD) and wet work being the most important risk factors. This study was launched to analyse the potential association between AD-related inflammation genes and development of non-atopic hand eczema among nurses in University Hospital. Atopic eczema, non-atopic hand dermatitis and control groups were identified. The association between occurrence of non-atopic hand eczema and interleukin (IL)-13, IL-4 and IL-5 gene variants was analysed. IL13 rs20541 A allele [assuming recessive model; odds ratio (OR) = 3.38, 95% CI: (1.63-7.00)] showed association with development of non-atopic hand eczema. Additive score analyses showed combination of this gene variant with previously identified risk factors including certain SPINK5 polymorphism and more than 10 years of work experience conferred highest risk for development of non-atopic hand eczema. As non-atopic hand eczema made up significant portion of occupational skin diseases, further studies should be focused on this commonly encountered skin condition.

  2. The Correlation between Gene Polymorphism and Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhao-Chun Chi; Chang-Xin Geng; Quan-Jiang Dong

    2013-01-01

    The association of gene polymorphism and susceptibility to hepatocellular carcinoma (HCC) has been widely studied in recent years. Gene mutations are closely related to HCC. Understanding and measuring the gene mutations are useful to reduce the incidence of HCC and improve its prognosis.

  3. Deletion of IL-4 receptor alpha on dendritic cells renders BALB/c mice hypersusceptible to Leishmania major infection.

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    Ramona Hurdayal

    2013-10-01

    Full Text Available In BALB/c mice, susceptibility to infection with the intracellular parasite Leishmania major is driven largely by the development of T helper 2 (Th2 responses and the production of interleukin (IL-4 and IL-13, which share a common receptor subunit, the IL-4 receptor alpha chain (IL-4Rα. While IL-4 is the main inducer of Th2 responses, paradoxically, it has been shown that exogenously administered IL-4 can promote dendritic cell (DC IL-12 production and enhance Th1 development if given early during infection. To further investigate the relevance of biological quantities of IL-4 acting on DCs during in vivo infection, DC specific IL-4Rα deficient (CD11c(creIL-4Rα(-/lox BALB/c mice were generated by gene targeting and site-specific recombination using the cre/loxP system under control of the cd11c locus. DNA, protein, and functional characterization showed abrogated IL-4Rα expression on dendritic cells and alveolar macrophages in CD11c(creIL-4Rα(-/lox mice. Following infection with L. major, CD11c(creIL-4Rα(-/lox mice became hypersusceptible to disease, presenting earlier and increased footpad swelling, necrosis and parasite burdens, upregulated Th2 cytokine responses and increased type 2 antibody production as well as impaired classical activation of macrophages. Hypersusceptibility in CD11c(creIL-4Rα(-/lox mice was accompanied by a striking increase in parasite burdens in peripheral organs such as the spleen, liver, and even the brain. DCs showed increased parasite loads in CD11c(creIL-4Rα(-/lox mice and reduced iNOS production. IL-4Rα-deficient DCs produced reduced IL-12 but increased IL-10 due to impaired DC instruction, with increased mRNA expression of IL-23p19 and activin A, cytokines previously implicated in promoting Th2 responses. Together, these data demonstrate that abrogation of IL-4Rα signaling on DCs is severely detrimental to the host, leading to rapid disease progression, and increased survival of parasites in infected

  4. Polymorphisms in the ALOX12 gene and osteoporosis

    DEFF Research Database (Denmark)

    Harsløf, T; Husted, Lise Bjerre; Nyegaard, Mette

    2011-01-01

    ALOX12 produces ligands for PPARγ thereby turning mesenchymal stem cells into adipocytes instead of osteoblasts. We investigated the effect of polymorphisms in the ALOX12 gene on BMD and fracture risk in two Danish cohorts and found four polymorphisms and a haplotype thereof to be associated...... with BMD and fracture risk. INTRODUCTION: Stimulation of the PPARγ with ligands produced by the ALOX enzymes drives mesenchymal stem cells in an adipocyte direction at the expense of osteoblasts leading to decreased osteoblast number and BMD. Previously, polymorphisms in the ALOX12 gene have been...... and followed for up to 10 years. On the basis of linkage disequilibrium (LD) between SNPs throughout the gene and previous genetic association studies we chose ten polymorphisms for investigation. Genotyping was carried out using the Sequenom MassARRAY genotyping system and TaqMan assays. RESULTS: In AROS...

  5. Renalase Gene Polymorphism in Patients After Renal Allograft Transplantation

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    Andrzej Pawlik

    2014-06-01

    Full Text Available Background/Aims: Renalase is a recently discovered protein, which is likely involved in regulation of blood pressure in humans and animals. Previous studies suggest that renalase reflects kidney functioning. A common missense polymorphism in the flavin-adenine dinucleotide-binding domain of human renalase (Glu37Asp has been described. In this study we examined the association between (Glu37Asp polymorphism (rs2296545 in renalase gene and kidney allograft function. Methods: The study enrolled 270 Caucasian kidney allograft recipients. SNP within the renalase was genotyped using TaqMan genotyping assays. Results: There were no statistically significant associations between renalase gene rs2296545 polymorphism and delayed graft function, acute rejection, chronic allograft dysfunction as well as creatinine serum concentrations and blood pressure values after transplantation. Conclusions: The results of this study suggest, that renalase gene rs2296545 polymorphism is not important factor determining renal allograft function.

  6. Association of peroxisome proliferator-activated receptor-gamma gene polymorphisms with the development of asthma.

    Science.gov (United States)

    Oh, Sun-Hee; Park, Se-Min; Lee, Yoo Hoon; Cha, Ji Yeon; Lee, Ji-Yeon; Shin, Eun Kyong; Park, Jong-Sook; Park, Byeong-Lae; Shin, Hyoung Doo; Park, Choon-Sik

    2009-07-01

    The peroxisome proliferator-activated receptors (PPAR) are the nuclear hormone receptor superfamily of ligand-activated transcriptional factors. PPAR-gamma (PPARG) activation downregulates production of Th2 type cytokines and eosinophil function. Additionally, treatment with a synthetic PPARG ligand can reduce lung inflammation and IFN-gamma, IL-4, and IL-2 production in experimental allergic asthma. In patients with asthma, PPARG gene expression is known to be associated with the airway inflammatory and remodeling responses. Thus, genetic variants of PPARG may be associated with the development of asthma. We genotyped two single nucleotide polymorphisms on the PPARG gene, +34C>G (Pro12Ala) and +82466C>T (His449His), in Korean subjects (839 subjects with asthma and 449 normal controls). Association analysis using logistic regression analysis showed that +82466C>T and haplotypes 1(CC) and 2(CT) were associated with the development of asthma (p=0.01-0.04). The frequency of PPARG-ht2 was significantly lower in the patients with asthma compared to the normal controls in codominant and dominant models (p=0.01, p(corr)=0.03 and p=0.02, p(corr)=0.03, respectively). Conversely, the frequency of PPARG-ht1 was significantly higher in the patients with asthma compared to the normal controls in the codominant model [p=0.04, OR: 1.27 (1.01-1.6)]. In addition, the rare allele frequency of +82466C>T was significantly lower in patients with asthma in comparison to normal controls in the codominant model (OR: 0.78, p=0.04). Thus, polymorphism of the PPARG gene may be linked to an increased risk of asthma development.

  7. Expression of POSTN, IL-4, and IL-13 in Chronic Rhinosinusitis with Nasal Polyps.

    Science.gov (United States)

    Milonski, Jaroslaw; Zielinska-Blizniewska, Hanna; Majsterek, Ireneusz; Przybyłowska-Sygut, Karolina; Sitarek, Przemyslaw; Korzycka-Zaborowska, Barbara; Olszewski, Jurek

    2015-05-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most frequently encountered chronic nasal diseases with a significant impact on patient quality of life. The aim of our study was therefore to investigate the association between the POSTN, IL-4, and IL-13 gene expression and the nasal polyp development. The objective of this study was to determine differential expression of POSTN, IL-4, and IL-13 genes in the mucosa and polyps of 63 patients with CRSwNP and 23 chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) when compared with patients with nasal septum deviation (n=18) who were used as controls. The expression level was investigated using reverse transcription-polymerase chain reaction assays in the polyp tissue and the mucosa of paranasal sinus collected while undergoing functional endoscopic sinus surgery. Expression of the mRNAs of all three genes, IL-4, IL-13, and POSTN, was significantly greater in the paired tissues of CRS patients with NPs or without NPs than in control subjects, with highest levels of POSTN and IL-13 seen in CRSwNP. An increased level of POSTN, IL-4, and IL-13 gene expression may be related to the development of chronic rhinosinusitis with nasal polyps, but polyp formation seemed to be associated especially with POSTN and IL-13 expression.

  8. Polimorfismos dos genes das citocinas regulatórias (IL-10 e TGF-β1), inflamatória (IL-4) e do receptor de vitamina D em relação aos fenótipos clínicos da alergia às proteínas do leite de vaca

    OpenAIRE

    Silva,Silvia Alves da

    2016-01-01

    A alergia às proteínas do leite de vaca (APLV) é definida como uma reação adversa imunologicamente mediada. A complexidade da APLV é observada tanto no espectro de apresentações clínicas como na sua história natural, e na sua etiologia, sobrepondo-se fatores genéticos e ambientais. O objetivo deste estudo foi analisar a frequência de polimorfismos nos genes das citocinas regulatórias (TGF-β1 e IL-10), inflamatória (IL-4) e no gene do receptor de vitamina D (VDR) em crianças com e sem APLV. A ...

  9. A Polymorphism in the IL-5 Gene is Associated with Inhibitor Development in Severe Hemophilia A Patients

    Directory of Open Access Journals (Sweden)

    İnanç Değer Fidancı

    2014-03-01

    Full Text Available OBJECTIVE: A severe complication in the replacement therapy of hemophilia A (HA patients is the development of alloantibodies (inhibitors against factor VIII, which neutralizes the substituted factor. The primary genetic risk factors influencing the development of inhibitors are F8 gene mutations. Interleukins and cytokines that are involved in the regulation of B-lymphocyte development are other possible targets as genetic risk factors. This study assesses the possible involvement of 9 selected single nucleotide gene polymorphisms (SNPs with interleukins (IL-4, IL-5, and IL-10, transforming growth factor beta 1 (TGF-β1, and interferon gamma (IFN-γ in inhibitor development in severely affected HA patients carrying a null mutation in the F8 gene. METHODS: A total of 173 HA patients were screened for intron 22 inversion and null mutations (nonsense and deletions. Genotyping of a total of 9 SNPs in genes IL-4, IL-5, IL-10, TGF-β1, and IFN-γ in 103 patients and 100 healthy individuals was carried out. RESULTS: An association analysis between 42 inhibitor (+ and 61 inhibitor (- patients showed a significant association with the T allele of rs2069812 in the IL-5 gene promoter and patients with inhibitors (p=0.0251. The TT genotype was also significantly associated with this group with a p-value of 0.0082, odds ratio of about 7, and confidence interval of over 90%, suggesting that it is the recessive susceptibility allele and that the C allele is the dominant protective allele. CONCLUSION: The lack of other variants in the IL-5 gene of patients and controls suggests that rs2069812 may be a regulatory SNP and may have a role in B-lymphocyte development, constituting a genetic risk factor in antibody development.

  10. Polymorphism in transmembrane region of MICA gene and cholelithiasis

    Science.gov (United States)

    Shih, Shou-Chuan; Lee, Yann-Jinn; Liu, Hsin-Fu; Dang, Ching-Wen; Chang, Shih-Chuan; Lin, Shee-Chan; Kao, Chin-Roa

    2003-01-01

    AIM: To study the significance of polymorphism of MHC class I chain-related gene A (MICA) gene in patients with cholelithiasis. METHODS: Subjects included 170 unrelated adults (83 males) with cholelithiasis and 245 randomly selected unrelated adults (130 males) as controls. DNA was extracted from peripheral leukocytes and analyzed for polymorphism of 5 alleles (A4, A5, A5.1, A6 and A9) of the MICA gene. RESULTS: There was no significant difference in phenotype, allele, and genotype frequencies of any of the 5 alleles between cholelithiasis patients and controls. CONCLUSION: This study demonstrates that MICA alleles studied bear no relation to cholelithiasis. PMID:12854159

  11. Polymorphism in transmembrane region of MTCA gene and cholelithiasis

    Institute of Scientific and Technical Information of China (English)

    Shou-Chuan Shih; Yann-Jinn Lee; Hsin-Fu Liu; Ching-Wen Dang; Shih-Chuan Chang; Shee-Chan Lin; Chin-Roa Kao

    2003-01-01

    AIM: To study the significance of polymorphism of MHC class I chain-related gene A (MICA) gene in patients with cholelithiasis.METHODS: Subjects included 170 unrelated adults (83males) with cholelithiasis and 245 randomly selected unrelated adults (130 males) as controls. DNA was extracted from peripheral leukocytes and analyzed for polymorphism of 5 alleles (A4, A5, A5.1, A6 and A9) of the MICA gene.RESULTS: There was no significant difference in phenotype,allele, and genotype frequencies of any of the 5 alleles between cholelithiasis patients and controls.CONCLUSION: This study demonstrates that MICA allelesstudied bear no relation to cholelithiasis.

  12. Polymorphic GGC repeat differentially regulates human reelin gene expression levels.

    Science.gov (United States)

    Persico, A M; Levitt, P; Pimenta, A F

    2006-10-01

    The human gene encoding Reelin (RELN), a pivotal protein in neurodevelopment, includes a polymorphic GGC repeat in its 5' untranslated region (UTR). CHO cells transfected with constructs encompassing the RELN 5'UTR with 4-to-13 GGC repeats upstream of the luciferase reporter gene show declining luciferase activity with increasing GGC repeat number (P autism.

  13. Human Multidrug Resistance 1 gene polymorphisms and Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Martinelli, Marcella; Scapoli, Luca; Pacilli, Angela Maria Grazia; Carbonara, Paolo; Girardi, Ambra; Mattei, Gabriella; Rodia, Maria Teresa; Solmi, Rossella

    2015-01-01

    Background: For the first time we tested an association between the human multidrug resistance gene 1 (MDR1) polymorphisms (SNPs) and idiopathic pulmonary fibrosis (IPF). Several MDR1 polymorphisms are associated with pathologies in which they modify the drug susceptibility and pharmacokinetics. Materials and Methods: We genotyped three MDR1 polymorphisms of 48 IPF patients and 100 control subjects with Italian origins. Results: No evidence of association was detected. Conclusion: There are 50 known MDR1 SNPs, and their role is explored in terms of the effectiveness of drug therapy. We consider our small-scale preliminary study as a starting point for further research. PMID:25767528

  14. IL-4 and IL-13 signaling in allergic airway disease.

    Science.gov (United States)

    Gour, Naina; Wills-Karp, Marsha

    2015-09-01

    Aberrant production of the prototypical type 2 cytokines, interleukin (IL)-4 and IL-13 has long been associated with the pathogenesis of allergic disorders. Despite tremendous scientific inquiry, the similarities in their structure, and receptor usage have made it difficult to ascertain the distinct role that these two look-alike cytokines play in the onset and perpetuation of allergic inflammation. However, recent discoveries of differences in receptor distribution, utilization/assembly and affinity between IL-4 and IL-13, along with the discovery of unique innate lymphoid 2 cells (ILC2) which preferentially produce IL-13, not IL-4, are beginning to shed light on these mysteries. The purpose of this chapter is to review our current understanding of the distinct roles that IL-4 and IL-13 play in allergic inflammatory states and the utility of their modulation as potential therapeutic strategies for the treatment of allergic disorders.

  15. 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.

  16. Signal transducer and activator of transcription 6 gene G2964A polymorphism and inflammatory bowel disease.

    NARCIS (Netherlands)

    Xia, B; Crusius, J.B.A.; Wu, J; Zwiers, A.; Bodegraven, van A.A.; Pena, A.S.

    2003-01-01

    Signal transducer and activator of transcription 6 (STAT6) is a key transcription factor involved in interleukin 4 (IL-4) and IL-13-mediated Th2 response. The STAT6 gene is located on chromosome 12q13.3-14.1 (IBD2 region) and is therefore a positional and functional candidate gene for study in infla

  17. Polymorphisms in immunoregulatory genes and the risk of histologic chorioamnionitis in Caucasoid women: a case control study

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    Heatley Susan L

    2005-02-01

    Full Text Available Abstract Background Chorioamnionitis is a common underlying cause of preterm birth (PTB. It is hypothesised that polymorphisms in immunoregulatory genes influence the host response to infection and subsequent preterm birth. The relationship between histologic chorioamnionitis and 22 single nucleotide polymorphisms in 11 immunoregulatory genes was examined in a case-control study. Methods Placentas of 181 Caucasoid women with spontaneous PTB prior to 35 weeks were examined for histologic chorioamnionitis. Polymorphisms in genes IL1A, IL1B, IL1RN, IL1R1, tumour necrosis factor (TNF, IL4, IL6, IL10, transforming growth factor beta-1 (TGFB1, Fas (TNFRSF6, and mannose-binding lectin (MBL2 were genotyped by polymerase chain reaction and sequence specific primers. Multivariable logistic regression including demographic and genetic variables and Kaplan-Meier survival analyses of genotype frequencies and pregnancy outcome were performed. Results Sixty-nine (34% women had histologic evidence of acute chorioamnionitis. Carriage of the IL10-1082A/-819T/592A (ATA haplotype [Multivariable Odds ratio (MOR 1.9, P = 0.05] and MBL2 codon 54Asp allele (MOR 2.0, P = 0.04, were positively associated with chorioamnionitis, while the TNFRSF6-1377A/-670G (AG haplotype (MOR 0.4, P = 0.03 and homozygosity for TGFB1-800G/509T (GT haplotype (MOR 0.2, P = 0.04 were negatively associated. Conclusion These findings demonstrate that polymorphisms in immunoregulatory genes IL10, MBL2, TNFRSF6 and TGFB1 may influence susceptibility to chorioamnionitis.

  18. Experimental neurocysticercosis: absence of IL-4 induces lower encephalitis

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    Hidelberto Matos Silva

    Full Text Available ABSTRACT Neurocysticercosis (NCC is the most severe clinical manifestation of cysticercosis. One of the factors responsible for its symptomatology is the host inflammatory response. Therefore the influence of interleukin 4 (IL-4 on the induction of encephalitis in experimental NCC was evaluated. Methods BALB/c (WT and BALB/c (IL-4-KO mice were inoculated intracranially with Taenia crassiceps cysticerci and euthanized at 7, 30, 60 and 90 days later, the encephala removed and histopathologically analyzed. Results The absence of IL-4 induced greater parasitism. In the initial phase of the infection, IL-4-KO showed a lower intensity in the inflammatory infiltration of polimorphonuclear cells in the host-parasite interface and intra-parenquimatous edema. The IL-4-KO animals, in the late phase of the infection, showed lower intensity of ventriculomegaly, encephalitis, and meningitis, and greater survival of the parasites in comparison with the WT animals. Conclusion The absence of IL-4 induced lower inflammatory infiltration, ventriculomegaly and perivasculitis in experimental NCC.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    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....... 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...... 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...

  20. Polymorphisms of candidate genes in Slovak autistic patients.

    Science.gov (United States)

    Kelemenova, Silvia; Schmidtova, Eva; Ficek, Andrej; Celec, Peter; Kubranska, Aneta; Ostatnikova, Daniela

    2010-08-01

    Autism is one of the most genetically influenced neuropsychiatric disorders. However, its detailed genetic basis is far from being clear. Genome-wide association studies have revealed a number of candidate genes, mostly related to synaptogenesis and various neuroendocrine pathways. In our study we have focused on oxytocin (OT), oxytocin receptor (OXTR), GABA receptor gamma 3 (GABRG3), neuroligin (NLGN4X), and reelin (RELN). After signed consent, 90 autistic boys and 85 healthy controls were enrolled in the study. Polymorphisms of OT (rs2740204), OXTR (rs2228485), GABRG3 (rs28431127), and NLGN4X (rs5916338) were analyzed using restriction fragment length polymorphism. (GGC)n STR polymorphism in the 5' UTR of the RELN gene was genotyped using fragment analysis. The only significant association in autistic boys in Slovakia was found with higher number of GGC repeats in the RELN gene (P=0.001) potentially explaining lower RELN levels in blood and brain of autistic patients.

  1. 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...

  2. Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms

    Directory of Open Access Journals (Sweden)

    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.

  3. [Clinical variations of chronic generalized periodontitis, genetic polymorphism and systemic production of inflammatory cytokines].

    Science.gov (United States)

    Grigorovich, E Sh; Pomorgailo, E G; Khomutova, E Yu; Stepanov, S S

    2015-01-01

    Carriage of polymorphic alleles of genes of cytokines-interleukines IL-1β, IL-1RN, TNFα, IL-4 can be a specific feature of chronic periodontitis patients. Genetic tests can be used to predict the course of the disease at its early manifestations. Objective: To establish the relationship of clinical manifestations of periodontal disease, inflammatory cytokines gene polymorphism and systemic levels of cytokine production. Periodontal tissue assessment and cone-beam computed tomography (CBCT) were performed in 150 periodontitis patients. A molecular--genetic testing for the presence of polymorphic alleles of genes IL-1β -511 C>T and +3953 C>T, IL-1RN (VNTR intron 2), IL-4 (VNTR intron 3), TNFα-308 G>A; content determined IL-1β, TNFα, IL-4 in peripheral blood was carried out in 150 patients with periodontitis and 150 healthy donors. Based on the analysis of the speed and nature of the supporting bone resorption and clinical manifestations patients are divided in "aggressive", "moderately progressive" and "slowly progressive" periodontits course groups. Disease severity was associated with distribution of genotypes and alleles of polymorphic genes cytokine IL-1RN (VNTR intron 2), TNFα-308 G>A and IL-4 (VNTR intron 3); haplotype IL-1β-511 TIL-1β +3953 T/IL-1RN 2R. There was no statistically significant difference in systemic level of IL-1β, TNFα and IL-4 between periodontitis groups but the donor level of cytokines was 2-4 times less.

  4. Serotonin transporter gene (5-HTT) polymorphisms and compulsive buying.

    Science.gov (United States)

    Devor, E J; Magee, H J; Dill-Devor, R M; Gabel, J; Black, D W

    1999-04-16

    We examined a panel of 21 patients diagnosed with compulsive buying for two DNA sequence polymorphisms found in the gene that encodes the serotonin transport (5-HTT). One polymorphism, found in the promoter region of the 5-HTT gene, involves a 44-base pair (bp) deletion, and the other, found in the second intron, is due to variable numbers of a repeat sequence. We also typed a panel of 38 psychiatrically normal controls for both 5-HH markers. When compared to this control panel, no significant differences were seen for either 5-HTT marker among the compulsive buyers.

  5. IL-4基因大白菜后代的分子检测及遗传分析%Molecular Detection and Genetic Analysis of Chinese Cabbage Progeny with the IL-4

    Institute of Scientific and Technical Information of China (English)

    金晓霞; 高亚; 于丽杰

    2013-01-01

    采用PPT抗性筛选、PCR扩增、PCR-Southern杂交、ELISA、Western杂交等方法,对花粉管通道法介导IL-4基因转化大白菜的后代进行了分子生物学检测,同时结合统计分析手段研究了IL-4基因在转基因大白菜后代中的遗传规律.结果表明:(1)PPT抗性的转基因大白菜,T4代植株PPT抗性的阳性率为33.43%,IL-4基因PCR扩增的阳性率为1.39%.IL-4的分离情况不符合孟德尔分离定律.(2)对T4代5个株系的14个PCR阳性株进行ELISA检测,其中有7份样品为阳性,IL-4表达量约为326.87 ~ 1233.13 ng/g FW,同一株系内各株间IL-4的表达量差异显著.(3) Western杂交进一步证实IL-4在转基因大白菜后代中能正常表达.PCR-southern杂交表明IL-4基因已整合到大白菜基因组中,且在转基因后代植株中仍然存在.%IL-4 gene transformation mediated by pollen-tube pathway method of Chinese cabbage for molecular detection of descendants using PPT resistance screening,PCR amplification,PCR-Southern hybrid,ELISA,Western hybrid methods,combined with statistical analysis study IL-4 inheritance of genes in transgenic Chinese cabbage in future generations.Results indicated that:(1) PPT resistance in transgenic Chinese cabbage,PPT resistance positive rates of T4 generation was 33.43%,the positive rate of PCR amplification of IL-4 gene was 1.39%.IL-4 separation plant does not meet Mendel' s law of segregation.(2) ELISA test on 14 ones of PCR-positive strains of 5 strains in the T4 generation,7 samples of which are positive,IL-4 expression was about 326.87 ~ 1233.13 ng/g FW,the ones of IL-4 expression within the same strains significance of difference.(3) Western confirmed IL-4 in transgenic Chinese cabbage hybrid offspring in the regular expression.It indicated that IL-4 gene has been incorporated into the Chinese cabbage in the genome with PCR-southern hybrid,and that gene still exists in transgenic plants' future generations.

  6. Cervical Carcinogenesis and Immune Response Gene Polymorphisms: A Review

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    Akash M. Mehta

    2017-01-01

    Full Text Available The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions with risk and progression of cervical cancer. Studies on HLA and KIR gene polymorphisms were excluded due to the abundance on literature on that subject. We show that multiple genes and loci are associated with variation in risk of cervical cancer. Rather than one single gene being responsible for cervical carcinogenesis, we postulate that variations in the different immune response genes lead to subtle differences in the effectiveness of the antiviral and antitumour immune responses, ultimately leading to differences in risk of developing cervical cancer and progressive disease after HPV infection.

  7. Cervical Carcinogenesis and Immune Response Gene Polymorphisms: A Review

    Science.gov (United States)

    Mooij, Merel

    2017-01-01

    The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV) infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions with risk and progression of cervical cancer. Studies on HLA and KIR gene polymorphisms were excluded due to the abundance on literature on that subject. We show that multiple genes and loci are associated with variation in risk of cervical cancer. Rather than one single gene being responsible for cervical carcinogenesis, we postulate that variations in the different immune response genes lead to subtle differences in the effectiveness of the antiviral and antitumour immune responses, ultimately leading to differences in risk of developing cervical cancer and progressive disease after HPV infection. PMID:28280748

  8. Polymorphism of the DNA Base Excision Repair Genes in Keratoconus

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    Katarzyna A. Wojcik

    2014-10-01

    Full Text Available Keratoconus (KC is a degenerative corneal disorder for which the exact pathogenesis is not yet known. Oxidative stress is reported to be associated with this disease. The stress may damage corneal biomolecules, including DNA, and such damage is primarily removed by base excision repair (BER. Variation in genes encoding BER components may influence the effectiveness of corneal cells to cope with oxidative stress. In the present work we genotyped 5 polymorphisms of 4 BER genes in 284 patients and 353 controls. The A/A genotype of the c.–1370T>A polymorphism of the DNA polymerase γ (POLG gene was associated with increased occurrence of KC, while the A/T genotype was associated with decreased occurrence of KC. The A/G genotype and the A allele of the c.1196A>G polymorphism of the X-ray repair cross-complementing group 1 (XRCC1 were associated with increased, and the G/G genotype and the G allele, with decreased KC occurrence. Also, the C/T and T as well as C/C genotypes and alleles of the c.580C>T polymorphism of the same gene displayed relationship with KC occurrence. Neither the g.46438521G>C polymorphism of the Nei endonuclease VIII-like 1 (NEIL1 nor the c.2285T>C polymorphism of the poly(ADP-ribose polymerase-1 (PARP-1 was associated with KC. In conclusion, the variability of the XRCC1 and POLG genes may play a role in KC pathogenesis and determine the risk of this disease.

  9. Relationship between TBX20 gene polymorphism and congenital heart disease.

    Science.gov (United States)

    Yang, X F; Zhang, Y F; Zhao, C F; Liu, M M; Si, J P; Fang, Y F; Xing, W W; Wang, F L

    2016-06-02

    Congenital heart disease in children is a type of birth defect. Previous studies have suggested that the transcription factor, TBX20, is involved in the occurrence and development of congenital heart disease in children; however, the specific regulatory mechanisms are yet to be evaluated. Hence, this study aimed to evaluate the relationship between the TBX20 polymorphism and the occurrence and development of congenital heart disease. The TBX20 gene sequence was obtained from the NCBI database and the polymorphic locus candidate was predicted. Thereafter, the specific gene primers were designed for the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) of DNA extracted from the blood of 80 patients with congenital heart disease and 80 controls. The results of the PCR were subjected to correlation analysis to identify the differences between the amplicons and to determine the relationship between the TBX20 gene polymorphism and congenital heart disease. One of the single nucleotide polymorphic locus was found to be rs3999950: c.774T>C (Ala265Ala). The TC genotype frequency in the patients was higher than that in the controls, similar to that for the C locus. The odds ratio of the TC genotypes was above 1, indicating that the presence of the TC genotype increases the incidence of congenital heart diseases. Thus, rs3999950 may be associated with congenital heart disease, and TBX20 may predispose children to the defect.

  10. In vivo regulation of the allergic response by the IL-4 receptor alpha chain immunoreceptor tyrosine-based inhibitory motif.

    Science.gov (United States)

    Tachdjian, Raffi; Al Khatib, Shadi; Schwinglshackl, Andreas; Kim, Hong Sook; Chen, Andrew; Blasioli, Julie; Mathias, Clinton; Kim, Hye Young; Umetsu, Dale T; Oettgen, Hans C; Chatila, Talal A

    2010-05-01

    Signaling by IL-4 and IL-13 through the IL-4 receptor alpha chain (IL-4Ralpha) plays a critical role in the pathology of allergic diseases. The IL-4Ralpha is endowed with an immunoreceptor tyrosine-based inhibitory motif (ITIM) centered on tyrosine 709 (Y709) in the cytoplasmic domain that binds a number of regulatory phosphatases. The function of the ITIM in the in vivo regulation of IL-4 receptor signaling remains unknown. We sought to determine the in vivo function of the IL-4Ralpha ITIM by using mice in which the ITIM was inactivated by mutagenesis of the tyrosine Y709 residue into phenylalanine (F709). F709 ITIM mutant mice were derived by means of knock-in mutagenesis. Activation of intracellular signaling cascades by IL-4 and IL-13 was assessed by means of intracellular staining of phosphorylated signaling intermediates and gene expression analysis. In vivo responses to allergic sensitization were assessed by using models of allergic airway inflammation. The F709 mutation increased signal transducer and activator of transcription 6 phosphorylation by IL-4 and, disproportionately, by IL-13. This was associated with exaggerated T(H)2 polarization, enhanced alternative macrophage activation by IL-13, augmented basal and antigen-induced IgE responses, and intensified allergen-induced eosinophilic airway inflammation and hyperreactivity. These results point to a physiologic negative regulatory role for the Y709 ITIM in signaling through IL-4Ralpha, especially by IL-13. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  11. Methylenetetrahydrofolate reductase gene polymorphism in Indian stroke patients

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    Kalita J

    2006-01-01

    Full Text Available Background and Aims: In view of the prevailing controversy about the role of Methylenetetrahydrofolate reductase (MTHFR C677T mutation in stroke and paucity of studies from India, this study has been undertaken to evaluate MTHFR C677T gene polymorphism in consecutive ischemic stroke patients and correlate these with folic acid, homocysteine (Hcy and conventional risk factors. Settings and Design: Ischemic stroke patients prospectively evaluated in a tertiary care teaching hospital. Materials and Methods: Computerized tomography proven ischemic stroke patients were prospectively evaluated including clinical, family history of stroke, dietary habits and addictions. Their fasting and postprandial blood sugar, lipid profile, vitamin B12, folic acid and MTHFR gene analysis were done. Statistical Analysis: MTHFR gene polymorphism was correlated with serum folic acid, Vitamin B12 and Hcy levels; family history of stroke in first-degree relatives; and dietary habits; employing Chi-square test. Results: There were 58 patients with ischemic stroke, whose mean age was 50 (4-79 years; among them, 10 were females. MTHFR gene polymorphism was present in 19 (32.8% patients, 3 were homozygous and 16 were heterozygous. Both serum folate and B12 levels were low in 29 (50% patients and Hcy in 48 (83%. Hypertension was present in 28 (48% patients, diabetes in 12 (21%, hyperlipidemia in 52 (90%, smoking in 17 (29%, obesity in 1 (1.7% and family history of stroke in first-degree relatives in 13 (22.4%. There was no significant relationship of MTHFR gene polymorphism with folic acid, B12, Hcy levels, dietary habits and number of risk factors. Vitamin B12 level was low in vegetarians ( P Conclusion: MTHFR gene polymorphism was found in one-third of patients with ischemic stroke and was insignificantly associated with higher frequency of elevated Hcy.

  12. 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.

  13. Polymorphisms in autophagy genes and susceptibility to tuberculosis.

    NARCIS (Netherlands)

    Songane, M.; Kleinnijenhuis, J.; Alisjahbana, B.; Sahiratmadja, E.; Parwati, I.; Oosting, M.; Plantinga, T.S.; Joosten, L.A.B.; Netea, M.G.; Ottenhoff, T.H.; Vosse, E. van de; Crevel, R. van

    2012-01-01

    Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana

  14. DNA polymorphism of HLA class II genes in alopecia areata

    DEFF Research Database (Denmark)

    Morling, N; Frentz, G; Fugger, L

    1992-01-01

    We investigated the DNA restriction polymorphism (RFLP) of the Major Histocompatibility Complex (MHC) class II genes: HLA-DQA, -DQB, -DPA, and -DPB in 20 Danish patients with alopecia areata (AA) and in healthy Danes. The frequency in AA of the DQB1*0301 and DQw7 associated DQB Bgl/II 4.2 kb...

  15. Multigenic control of measles vaccine immunity mediated by polymorphisms in measles receptor, innate pathway, and cytokine genes.

    Science.gov (United States)

    Kennedy, Richard B; Ovsyannikova, Inna G; Haralambieva, Iana H; O'Byrne, Megan M; Jacobson, Robert M; Pankratz, V Shane; Poland, Gregory A

    2012-03-09

    Measles infection and vaccine response are complex biological processes that involve both viral and host genetic factors. We have previously investigated the influence of genetic polymorphisms on vaccine immune response, including measles vaccines, and have shown that polymorphisms in HLA, cytokine, cytokine receptor, and innate immune response genes are associated with variation in vaccine response but do not account for all of the inter-individual variance seen in vaccinated populations. In the current study we report the findings of a multigenic analysis of measles vaccine immunity, indicating a role for the measles virus receptor CD46, innate pattern-recognition receptors (DDX58, TLR2, 4, 5, 7 and 8) and intracellular signaling intermediates (MAP3K7, NFKBIA), and key antiviral molecules (VISA, OAS2, MX1, PKR) as well as cytokines (IFNA1, IL4, IL6, IL8, IL12B) and cytokine receptor genes (IL2RB, IL6R, IL8RA) in the genetic control of both humoral and cellular immune responses. This multivariate approach provided additional insights into the genetic control of measles vaccine responses over and above the information gained by our previous univariate SNP association analyses.

  16. Matrix metalloproteinase gene polymorphisms in patients with coronary artery disease

    Directory of Open Access Journals (Sweden)

    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.

  17. Two polymorphisms in the glucocorticoid receptor gene directly affect glucocorticoid-regulated gene expression.

    NARCIS (Netherlands)

    H. Russcher (Henk); P. Smit (Pauline); E.L.T. van den Akker (Erica); E.F.C. van Rossum (Liesbeth); A.O. Brinkmann (Albert); F.H. de Jong (Frank); S.W.J. Lamberts (Steven); J.W. Koper (Jan)

    2005-01-01

    textabstractCONTEXT: Interindividual variation in glucocorticoid (GC)-sensitivity can be partly explained by polymorphisms in the GC receptor (GR) gene. The ER22/23EK and N363S polymorphisms have been described to be associated with lower and higher GC sensitivity, respectively. OBJECTIVE AND DESIGN

  18. Androgen receptor gene mutation, rearrangement, polymorphism.

    Science.gov (United States)

    Eisermann, Kurtis; Wang, Dan; Jing, Yifeng; Pascal, Laura E; Wang, Zhou

    2013-09-01

    Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents.

  19. Polymorphisms in the Human SNAIL (SNAI1) gene.

    Science.gov (United States)

    Okajima, K; Paznekas, W A; Burstyn, T; Jabs, E W

    2001-02-01

    The human SNAIL is an important developmental protein involved in the formation of mesoderm and neural crest. The protein contains three classic and one atypical zinc-finger motif. The SNAI1 gene is composed of three exons. We have identified three SNPs in non-coding regions, two in the 5'UTR and one in intron 1, which can be detected by PCR followed by restriction enzyme digestion. We also identified a GGG/GGGG polymorphism in intron 1. We screened CEPH DNAs for these polymorphisms. Copyright 2001 Academic Press.

  20. Association of GST Genes Polymorphisms with Asthma in Tunisian Children

    Directory of Open Access Journals (Sweden)

    Chelbi Hanene

    2007-01-01

    Objective. We assessed whether polymorphisms of GST genes (GSTM1, GSTT1, and GSTP1 are associated with asthma and atopy among Tunisian children. Methods. 112 unrelated healthy individuals and 105 asthmatic (73 atopic and 32 nonatopic children were studied. Genotyping the polymorphisms in the GSTT1 and GSTM1 genes was performed using the multiplex PCR. The GSTP1 ILe105Val polymorphism was determined using PCR-RFLP. Results. GSTM1 null genotype was significantly associated with the increased risk of asthma (P=.002. Asthmatic children had a higher prevalence of the GSTP1Ile105 allele than the control group (43.8% and 33.5%, respectively; P=.002. Also, the presence of the GSTP1 homozygote Val/Val was less common in subjects with asthma than in control group. We have found that GSTT1 null genotype (GSTT10∗/0∗ was significantly associated with atopy (P=.008. Conclusion. Polymorphisms within genes of the GST superfamily were associated with risk of asthma and atopy in Tunisia.

  1. GSTM1, GSTT1 and GSTP1 gene polymorphism in polymorphous light eruption.

    Science.gov (United States)

    Zirbs, M; Pürner, C; Buters, J T M; Effner, R; Weidinger, S; Ring, J; Eberlein, B

    2013-02-01

    Polymorphous light eruption (PLE) is the most common chronic and idiopathic photodermatosis. PLE is assumed to represent an immunological hypersensitivity reaction to a radiation-induced cutaneous antigen involving reactive oxygen species (ROS) on the basis of a genetic predisposition. Among others, cellular protection against ROS is provided by glutathione S-transferases (GSTs). Different variants of the GST enzymes may influence the activity and efficiency of detoxification and biotransformation of unknown UV-induced skin-antigens and other factors that may play an important role in the pathogenesis of PLE. In this study the relationship between isoenzymes of the GST genes GSTM1, GSTT1 and GSTP1 and possible protective or predisposing effects on PLE was examined in 29 patients and 144 controls. Diagnosis of PLE was based on the presence of characteristic clinical features. No association between the functional polymorphisms of the GST gene family and PLE was found. Prevalence of certain GST isoenzymes or polymorphisms in patients with PLE did not differ from healthy controls. Our data do not support prevalence of GST isoenzymes or polymorphisms as a protective effect against PLE. Especially a higher carrier frequency of GSTP1 Val(105) as a protective factor against PLE which has been published before could not be proved. The GST genotypes GSTM1, GSTT1 and GSTP1 (including SNPs) seem to have no relevant association with PLE. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  2. Association between serotonin transporter gene polymorphism and recurrent aphthous stomatitis

    Science.gov (United States)

    Manchanda, Aastha; Iyengar, Asha R.; Patil, Seema

    2016-01-01

    Background: Anxiety-related traits have been attributed to sequence variability in the genes coding for serotonin transmission in  the brain. Two alleles, termed long (L) and short (S) differing by 44 base pairs, are found in a polymorphism identified in the promoter region of serotonin transporter gene. The presence of the short allele  and SS and LS genotypes is found to be associated with the reduced expression of this gene decreasing the uptake of serotonin in the brain leading to various anxiety-related traits. Recurrent aphthous stomatitis (RAS) is an oral mucosal disease with varied etiology including the presence of stress, anxiety, and genetic influences. The present study aimed to determine this serotonin transporter gene polymorphism in patients with RAS and compare it with normal individuals. Materials and Methods: This study included 20 subjects with various forms of RAS and 20 normal healthy age- and gender-matched individuals. Desquamated oral mucosal cells were collected for DNA extraction and subjected to polymerase chain reaction for studying insertion/deletion in the 5-HTT gene-linked polymorphic region. Cross tabulations followed by Chi-square tests were performed to compare the significance of findings, P < 0.05 was considered statistically significant. Results: The LS genotype was the most common genotype found in the subjects with aphthous stomatitis (60%) and controls (40%). The total percentage of LS and SS genotypes and the frequency of S allele were found to be higher in the subjects with aphthous stomatitis as compared to the control group although a statistically significant correlation could not be established, P = 0.144 and 0.371, respectively. Conclusion: Within the limitations of this study, occurrence of RAS was not found to be associated with polymorphic promoter region in serotonin transporter gene. PMID:27274339

  3. A pilot study of Helicobacter pylori genotypes and cytokine gene polymorphisms in reflux oesophagitis and peptic ulcer disease.

    Science.gov (United States)

    Akdogan, R A; Ozgur, O; Gucuyeter, S; Kaklikkaya, N; Cobanoglu, U; Aydin, F

    2014-01-01

    Helicobacter pylori causes various diseases such as chronic gastritis, peptic ulcer and gastric cancer. While majority of the people infected with H. pylori is asymptomatic, 15-20 % of them develop such diseases. The main factors, which determine the development of H. pylori related diseases might be bacterial virulence, host genetic and environmental factors.The aim of this study was to reveal the factors that play a role in the disease development in patients with reflux esophagitis and peptic ulcer, infected with Helicobacter pylori. Environmental factors such as medical agents, smoking and body mass index were evaluated. The factors specific to bacteria such as vacA, CagA, babA and iceA virulence genotypes and the host factors such as IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, interferon-γ, TNF-α, ve TGF-β1 gene polymorphisms were compared between the two groups.H. pylori infected twenty five patients with reflux esophagitis and peptic ulcer were enrolled in the study. There was no statistical difference between the two groups regarding environmental factors. IL-2 -330T +166T (p=0.037) and IL10 -1082A; -819C (p=0.049) gene polymorphisms were significantly more common in the group of patients with peptic ulcer compared to the group with reflux esophagitis. In both groups of patients, either with reflux esophagitis or peptic ulcer, multiple H. pylori virulence genotypes (cagA, vacA, babA) (mean values 74 %, 78 %, 54 % respectively) were observed.In this study, we revealed that cytokine gene polymorphisms may play a role in the development peptic ulcer while H. pylori virulence genotypes seem to be crucial for the development of associated diseases (Tab. 4, Ref. 51).

  4. Polymorphism of exon 3 of the HLA-G gene

    DEFF Research Database (Denmark)

    Hviid, T V; Meldgaard, Michael; Sørensen, S

    1997-01-01

    populations have only revealed a limited polymorphism. We investigated the polymorphism of the exon 3 of HLA-G by means of Polymerase Chain Reaction (PCR)-Single Strand Conformation Polymorphism (SSCP)- and DNA sequencing analysis in a Danish population. We detected four single-base substitutions in exon 3...... rate of embryos. HLA-G seems to play an important role in the feto-maternal relationship. The polymorphism of the HLA-G locus is not fully clarified. One study has shown extensive nucleotide sequence variation in the exon 3 (alpha-2 domain) in healthy African Americans. A few studies in other...... compared to the sequence of HLA-6.0 (G*01011); one of these has not been reported before. We also found a deletion of the first base of codon 130 or the third of codon 129 in a heterozygous individual. This study, together with previous results, suggests that the polymorphism of exon 3 of the HLA-G gene...

  5. Glucocorticoid receptor gene polymorphism and juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    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

  6. Frequencies of single nucleotide polymorphisms in genes regulating inflammatory responses in a community-based population

    Directory of Open Access Journals (Sweden)

    Comstock George W

    2007-03-01

    Full Text Available Abstract Background Allele frequencies reported from public databases or articles are mostly based on small sample sizes. Differences in genotype frequencies by age, race and sex have implications for studies designed to examine genetic susceptibility to disease. In a community-based cohort of 9,960 individuals, we compared the allele frequencies of 49 single nucleotide polymorphisms (SNPs of genes involved in inflammatory pathways to the frequencies reported on public databases, and examined the genotypes frequencies by age and sex. The genes in which SNPs were analyzed include CCR2, CCR5, COX1, COX2, CRP, CSF1, CSF2, IFNG, IL1A, IL1B, IL2, IL4, IL6, IL8, IL10, IL13, IL18, LTA, MPO, NOS2A, NOS3, PPARD, PPARG, PPARGC1 and TNF. Results Mean(SD age was 53.2(15.5; 98% were Caucasians and 62% were women. Only 1 out of 33 SNPs differed from the SNP500Cancer database in allele frequency by >10% in Caucasians (n = 9,831, whereas 12 SNPs differed by >10% (up to 50% in African Americans (n = 105. Two out of 15 SNPs differed from the dbSNP database in allele frequencies by >10% in Caucasians, and 5 out of 15 SNPs differed by >10% in African Americans. Age was similar across most genotype groups. Genotype frequencies did not differ by sex except for TNF(rs1799724, IL2(rs2069762, IL10(rs1800890, PPARG(rs1801282, and CRP(rs1800947 with differences of less than 4%. Conclusion When estimating the size of samples needed for a study, particularly if a reference sample is used, one should take into consideration the size and ethnicity of the reference sample. Larger sample size is needed for public databases that report allele frequencies in non-Caucasian populations.

  7. The Interleukin-13 Receptor-α1 Chain Is Essential for Induction of the Alternative Macrophage Activation Pathway by IL-13 but Not IL-4.

    Science.gov (United States)

    Sheikh, Faruk; Dickensheets, Harold; Pedras-Vasconcelos, Joao; Ramalingam, Thirumalai; Helming, Laura; Gordon, Siamon; Donnelly, Raymond P

    2015-01-01

    Macrophages coexpress both the interleukin (IL)-2Rγ chain (γ(c)) and IL-13Rα1. These receptor chains can heterodimerize with IL-4Rα to form type I or type II IL-4 receptor complexes, respectively. We used macrophages derived from Il2rg and Il13ra1 knockout (KO) mice to evaluate the requirements for these receptor chains for induction of the alternative macrophage activation (AMA) pathway by IL-4 and IL-13. Absence of γ(c) significantly decreased activation of STAT6 by IL-4 but not IL-13. However, although activation of STAT6 by IL-4 was markedly reduced in γ(c) KO macrophages, it was not abolished, indicating that IL-4 can still signal through type II IL-4 receptors via the IL-13Rα1 chain. IL-13 failed to activate STAT6 in macrophages derived from Il13ra1 KO mice; however, these cells remained fully responsive to IL-4. The inability of IL-13 but not IL-4 to signal in Il13ra1(-/-) macrophages correlated with the inability of IL-13 but not IL-4 to induce expression of genes such as Arg1, Retnla and Ccl11 that are characteristically expressed by alternatively activated macrophages. In addition, IL-13 but not IL-4 failed to induce membrane fusion and giant cell formation by Il13ra1 KO macrophages. These findings demonstrate that the IL-13Rα1 chain is essential for induction of the AMA pathway by IL-13 but not IL-4.

  8. Metabolic gene polymorphism frequencies in control populations

    DEFF Research Database (Denmark)

    Garte, Seymour; Gaspari, Laura; Alexandrie, Anna-Karin

    2001-01-01

    Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT...

  9. Apolipoprotein E gene polymorphisms as risk factors for carotid atherosclerosis

    Directory of Open Access Journals (Sweden)

    Zurnić Irena

    2014-01-01

    Full Text Available Background/Aim. Atherosclerosis is still the leading cause of death in Western world. Development of atherosclerotic plaque involves accumulation of inflammatory cells, lipids, smooth muscle cells and extracellular matrix proteins in the intima of the vascular wall. Apolipoprotein E participates in the transport of exogenous cholesterol, endogenouly synthesized lipids and triglycerides in the organism. Apolipoprotein E gene has been identified as one of the candidate genes for atherosclerosis. Previous studies in different populations have clearly implicated apolipoprotein E genetic variation (ε polymorphisms as a major modulator of low density lipoprotein cholesterol levels. Data considering apolipoprotein E polymorphisms in relation to carotid atherosclerosis gave results that are not in full compliance. The aim of present study was to investigate the apolipoprotein E polymorphisms in association with carotid plaque presence, apolipoprotein E and lipid serum levels in patients with carotid atherosclerosis from Serbia. Methods. The study group enrolled 495 participants: 285 controls and 210 consecutive patients with carotid atherosclerosis who underwent carotid endarterectomy. Genotyping of apolipoprotein E polymorphisms were done using polymerase chain reaction and restriction fragment length polymorphism methods. Results. Patients had significantly decreased frequency of the ε2 allele compared to controls. Patients who carry at least one ε2 allele had a significantly higher level of serum apolipoprotein E and significantly lower low density lipoprotein cholesterol levels compared to those who do not carry this allele. Conclusion. Our results suggest protective effect of apolipoprotein E ε2 allele on susceptibility for carotid plaque presence as well as low density lipoprotein cholesterol lowering effect in Serbian patients with carotid atherosclerosis. Further research of multiple gene and environmental factors that contribute to the

  10. Candidate gene polymorphisms and their association with hypertension in Malays.

    Science.gov (United States)

    Ghazali, Dzuzaini M; Rehman, Asia; Rahman, Abdul Rashid A

    2008-02-01

    Knowledge of candidate gene polymorphisms in a population is useful for a variety of gene-disease association studies, particularly for some complex traits. A single nucleotide variant of the angiotensinogene gene (AGT M235T) and endothelial nitric oxide synthase gene (eNOS G894T) have been associated with hypertension. A cross-sectional study consisting of 200 hypertensives and 198 age- and sex-matched controls was conducted. Subjects involved in this study were pure Malay for 3 generations. The AGT M235T and eNOS G894T polymorphisms were determined by PCR-RFLP method. The distribution of M235T genotype in the population was 3.5% for MM, 30.4% for MT and 66.1% for TT. No significant difference was observed in genotype (chi(2)=1.30, p=0.52) and allele (chi(2)=0.87, p=0.35) frequencies among the 2 study group. In contrast, the distribution of genotypes for G894T was 74.1% for GG, 24.6% for GT and 1.3% for TT, respectively. Similarly, no significant difference was observed in genotype (chi(2)=0.94, p=0.33) and allele (chi(2)=0.60, p=0.44) frequencies between both study groups. The AGT M235T and eNOS G894T polymorphisms are unlikely to play an important role in the pathogenesis of hypertension in Malays.

  11. Determination of alpha-2-MRAP gene polymorphisms in nephrolithiasis patients.

    Science.gov (United States)

    Mehde, Atheer Awad; Mehdi, Wesen Adel; Yusof, Faridah; Raus, Raha Ahmed; Abidin, Zaima Azira Zainal; Ghazali, Hamid; Rahman, Azlina Abd

    2017-07-29

    The intron 5 insertion/deletion polymorphism of Alpha-2-macroglobulin receptor-associated protein gene (Alpha-2-MRAP) has been implicated in numerous diseases. The current study was designed to analyze the association of intron 5 insertion/deletion polymorphism of Alpha-2-MRAP with nephrolithiasis patients. PCR was conducted on genomic DNA of patients and control to look for Alpha-2-MRAP insertion/deletion polymorphism. Besides that, serum level of Alpha-2-MRAP, oxidative stress marker myeloperoxidase, Malondialdehyde (MDA), Advanced oxidation protein products (AOPP), and uric acid were determined. The D and I allele frequencies were 57.50% and 42.50% in patients, 77.50% and 22.50% in control, individually. The result showed that II genotype was associated with nephrolithiasis patients group. A significant decrease was observed in serum Alpha-2-MRAP,myeloperoxidase and TAS,while TOS,OSI,MDA,AOPP and uric acid were substantially increased in II and ID when compared to DD genotype in patients with nephrolithiasis. Our results demonstrate for the first time that patients with II genotype had an increased risk of stones. Also, the results demonstrate that I allele of the 5 insertion/deletion polymorphism in the Alpha-2-MRAP gene is related with an increase of oxidative stress in nephrolithiasis patients and may possibly impose a risk for cardiovascular diseases in patients with II genotype of Alpha-2-MRAP. Copyright © 2017. Published by Elsevier B.V.

  12. Investigation of the therapeutic efficacy of codelivery of psiRNA-vascular endothelial growth factor and pIL-4 into chitosan nanoparticles in the breast tumor model.

    Science.gov (United States)

    Şalva, Emine; Turan, Suna O; Kabasakal, Levent; Alan, Saadet; Özkan, Naziye; Eren, Fatih; Akbuğa, Jülide

    2014-03-01

    Angiogenesis has been known to increase tumor growth and for its metastatic potential in human tumors. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and is a promising therapeutic target for breast cancer. VEGF is an essential target for RNAi-based gene therapy of breast cancer. Interleukin-4 (IL-4) may act as an anti-angiogenic molecule that inhibits tumor growth and migration in rats. The purpose of the present study was to improve therapeutic efficacy in breast cancer with the codelivery of siRNA-expressing plasmid targeting VEGF and IL-4-expressing plasmid encapsulating into chitosan nanoparticles (NPs). The codelivery of psiVEGF and pIL-4 plasmids greatly enhanced in vitro and in vivo gene-silencing efficiency. For the in vitro study, when psiVEGF and pIL-4 into chitosan NPs were combined (81%), the gene-silencing effect was higher than psiVEGF and pIL-4 NPs alone. The in vivo study breast tumor model demonstrated that the administration of coencapsulation of psiVEGF and pIL-4 into chitosan NPs caused an additive effect on breast tumor growth inhibition (97%), compared with containing NPs psiVEGF or pIL-4 alone. These results indicate that chitosan NPs can be effectively used for the codelivery of pIL-4 and siVEGF-expressing plasmid in a combination therapy against breast cancer.

  13. Simultaneous detection of the exon 10 polymorphism and a novel intronic single base insertion polymorphism in the XPD gene using single strand conformation polymorphism.

    Science.gov (United States)

    Kumar, Rajiv; Angelini, Sabrina; Hemminki, Kari

    2003-03-01

    We developed a new method based on the single strand conformation polymorphism (SSCP) technique for the detection of a G23591A (Asp312Asn) polymorphism in exon 10 of the XPD gene. In the process we also identified a novel polymorphism 23623C-ins (IVS10+17C-ins) in intron 10 of the same gene. With this newly developed SSCP-based method of genotyping we could detect both polymorphisms in the same assay and thus consequently determine the haplotype. In order to determine the population frequency of the novel polymorphism and the haplotype frequency, 302 healthy individuals were genotyped. The allelic frequency of the 23623C-ins intronic polymorphism was 0.16, whereas the frequency of the variant allele for the G23591A polymorphism was 0.39. Forty-three individuals (14%) were heterozygous for both polymorphisms but none carried polymorphic variants for both G23591A and 23623C-ins on the same allele. The effect of the novel intronic insertion polymorphism, which is located 16 nt downstream of the 3'-end of exon 10 of the XPD gene and involves a mononucleotide C repeat sequence, on expression remains to be determined.

  14. Research progress of the correlation between gene polymorphism and stroke

    Directory of Open Access Journals (Sweden)

    Gao-yu CAI

    2015-03-01

    Full Text Available Stroke is a common disease which has serious impact on human health in modern society. It has complex pathogenesis and wide-ranging influencing factors. Accompanied with the development of molecular genetics, a number of single nucleotide polymorphisms (SNPs have been found to be closely related to the incidence of stroke in case-control studies on the correlation between genes and stroke by using molecular biology technologies. In order to have a better understanding on the correlation between gene polymorphism and stroke, this summary presents a review of literatures reported at home and abroad over the past year on the genetics of stroke. DOI: 10.3969/j.issn.1672-6731.2015.02.002

  15. Surfactant gene polymorphisms and interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Pantelidis Panagiotis

    2001-11-01

    Full Text Available Abstract Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs. Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

  16. Interleukin 17 Receptor Gene Polymorphism in Periimplantitis and Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    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.

  17. Relation between ADIPOQ Gene Polymorphisms and Type 2 Diabetes

    OpenAIRE

    Zhi-Peng Li; Mei Zhang; Jie Gao; Guo-Yan Zhou; Shuang-Qing Li; Zhen-Mei An

    2015-01-01

    Objective: The manuscript investigates the relation between adiponectin gene (ADIPOQ) polymorphisms and type 2 diabetes mellitus (T2DM) in a Chinese population. Methods: We designed a case-control study involving 340 normal glucose tolerant (NGT) subjects and 340 type 2 diabetes patients. Three SNPs (rs182052, rs1501299, and rs7627128) were genotyped by TaqMan methods. Results: We found that rs7627128, rs1501299 and rs182052 were significantly associated with T2DM. Haplotypes analysis indicat...

  18. Interleukin 17 receptor gene polymorphism in periimplantitis and chronic periodontitis.

    Directory of Open Access Journals (Sweden)

    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.

  19. The relationship between MAOA gene polymorphism and test anxiety.

    Science.gov (United States)

    Liu, Yangyang; Lu, Zuhong

    2013-12-01

    In a sample of 569 Chinese high school students, the present findings indicated that students with the 4-repeat genotype showed a higher level of test anxiety. Furthermore, the prediction of academic performance on test anxiety was stronger among students with the 3-repeat genotype than those with the 4-repeat genotype. The present findings suggest that mono-amine-oxidase type A gene polymorphism is significantly related to test anxiety.

  20. Interleukin 17 receptor gene polymorphism in periimplantitis and chronic periodontitis.

    Science.gov (United States)

    Kadkhodazadeh, Mahdi; Ebadian, Ahmad Reza; Amid, Reza; Youssefi, Navid; Mehdizadeh, Amir Reza

    2013-07-13

    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.

  1. SIRT1 gene polymorphisms and risk of lung cancer

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    Lv Y

    2017-09-01

    Full Text Available Yanbo Lv, Shuangyan Lin, Fang Peng Department of Pathology, Zhejiang Hospital, Hangzhou City, Zhejiang, China Objective: Lung cancer, which is the leading cause of cancer death worldwide, is influenced by a wide variety of environmental and genetic risk factors. The silent information regulator 1 (SIRT1 gene is located on the long arm of chromosome 10 (10q21.3 and has been shown to play crucial roles in lung cancer development in previous studies. In this study, we determined whether variation in the SIRT1 gene is associated with lung cancer in Chinese population.Methods: The case–control study comprised 246 controls and 257 non-small cell lung cancer patients, comprising 79 squamous cell carcinoma patients and 124 adenocarcinoma patients. All subjects were from Zhejiang, China. Four single-nucleotide polymorphisms of SIRT1 gene were analyzed: rs12778366 (C/T, lies in the 5′ upstream, rs3758391 (C/T, lies in the 5′ upstream, rs2273773 (C/T, lies in the coding and rs4746720 (C/T, lies in the 3′ untranslated region.Results: No significant difference of allele and genotype frequencies was observed between the different groups. Haplotype association analysis carried out on the four single-nucleotide polymorphisms within the case–control cohort also did not reveal a significant association with lung cancer (P>0.05.Conclusion: The results suggest the tested SIRT1 gene polymorphisms may not contribute to lung cancer. Further studies are warranted to demonstrate the functional roles of the SIRT1 polymorphism in lung cancer. Keywords: SIRT1, SNP, non-small cell lung cancer, adenocarcinoma, squamous cell carcinoma

  2. Polymorphic cis- and trans-regulation of human gene expression.

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    Vivian G Cheung

    Full Text Available Expression levels of human genes vary extensively among individuals. This variation facilitates analyses of expression levels as quantitative phenotypes in genetic studies where the entire genome can be scanned for regulators without prior knowledge of the regulatory mechanisms, thus enabling the identification of unknown regulatory relationships. Here, we carried out such genetic analyses with a large sample size and identified cis- and trans-acting polymorphic regulators for about 1,000 human genes. We validated the cis-acting regulators by demonstrating differential allelic expression with sequencing of transcriptomes (RNA-Seq and the trans-regulators by gene knockdown, metabolic assays, and chromosome conformation capture analysis. The majority of the regulators act in trans to the target (regulated genes. Most of these trans-regulators were not known to play a role in gene expression regulation. The identification of these regulators enabled the characterization of polymorphic regulation of human gene expression at a resolution that was unattainable in the past.

  3. Effect of gene polymorphisms on periodontal diseases

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    Fouzia Tarannum

    2012-01-01

    Full Text Available Periodontal diseases are inflammatory diseases of supporting structures of the tooth. It results in the destruction of the supporting structures and most of the destructive processes involved are host derived. The processes leading to destruction and regeneration of the destroyed tissues are of great interest to both researchers and clinicians. The selective susceptibility of subjects for periodontitis has remained an enigma and wide varieties of risk factors have been implicated for the manifestation and progression of periodontitis. Genetic factors have been a new addition to the list of risk factors for periodontal diseases. With the availability of human genome sequence and the knowledge of the complement of the genes, it should be possible to identify the metabolic pathways involved in periodontal destruction and regeneration. Most forms of periodontitis represent a life-long account of interactions between the genome, behaviour, and environment. The current practical utility of genetic knowledge in periodontitis is limited. The information contained within the human genome can potentially lead to a better understanding of the control mechanisms modulating the production of inflammatory mediators as well as provides potential therapeutic targets for periodontal disease. Allelic variants at multiple gene loci probably influence periodontitis susceptibility.

  4. 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.

  5. Cloning, expression, and polymorphism of the porcine calpain10 gene

    Institute of Scientific and Technical Information of China (English)

    Xiuqin Yang; Di Liu; Hao Yu; Lijuan Guo; Hui Liu

    2008-01-01

    Calpains are calcium-regulated protcases involved in cellular functions that include muscle proteolysis both ante- and postmortem. This study was designed to clone the complete coding sequence of the porcine calpain10 gene, CAPN10, to analyze its expression characteristics and to investigate its polymorphism. Two isoforms of the CAPN10 gene, CAPN10A and CAPN10B, were obtained by reverse transcriptionpolymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends methods combined with in silico cloning. RT-PCR results indicated that CAPN10 mRNA was ubiquitously expressed in all tissues examined and, with increasing age,the expression level increased in muscles at six different growth points. In the same tissues, the expression level of CAPN10A was higher than that of CAPN10B. In addition,three single nucleotide polymorphisms were detected by the PCR-single-stranded conformational polymorphism method and by comparing the sequences of Chinese Min pigs with those of Yorkshire pigs. C527T mutation was a missense mutation and led to transforming Pro into Leu at the 176th amino acid. The results of the current study provided basic molecular information for further study of the function of the porcine CAPN10 gene.

  6. Retrovirus-mediated delivery of an IL-4 receptor antagonist inhibits allergic responses in a murine model of asthma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This work reports the investigation of the effect of airway IL-4RA gene transfer by a recombinant retroviral vector on airway inflammation and airway responsiveness in asthmatic mice. The retrovirus-mediated delivery of IL-4RA to the airways of mice inhibited elevations of airway responsiveness and the development of allergic inflammation in asthmatic mice, and regulated the Th1/Th2 balance in OVA-sensitized and -challenged mouse models. This suggests that gene therapy is a therapeutic option for treating and controlling chronic airway inflammation and asthma symptoms.

  7. Estrogenic receptors a and p gene polymorphisms in postmenopausal osteoporosis

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    K A Maslova

    2008-01-01

    Full Text Available Objective. To assess frequency distribution of estrogenic receptor (ERa and ERfl gene polymorphisms and their influence on bone mineral density (BMD in groups of postmenopausal women with and without osteoporosis (OP. Material and methods. 200 residents of Moscow and Moscow region were divided into two groups considering BMD values according to WHO criteria; OP group and healthy control group Results. Differences of genotype and their combinations frequency distribution between OP and control groups show presence OP risk and protector genotypes. ER gene important role in pathogenesis of postmenopausal osteoporosis and possibility to use these genetic markers for assessment of risk of OP development in Russian population was confirmed.

  8. 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 genotyping seven SNPs in 294, 342 and 100 families from Denmark, United Kingdom and Norway and conducting family-based association analyses for asthma, atopic asthma and bronchial hyper-reactivity (BHR) phenotypes. Three SNPs in IL18R1 were associated with asthma (0.01131 ... in IL18R1 and asthma....

  9. Identification of novel single nucleotide polymorphisms in inflammatory genes as risk factors associated with trachomatous trichiasis.

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    Berna Atik

    Full Text Available BACKGROUND: Trachoma is the leading preventable cause of global blindness. A balanced Th1/Th2/Th3 immune response is critical for resolving Chlamydia trachomatis infection, the primary cause of trachoma. Despite control programs that include mass antibiotic treatment, reinfection and recurrence of trachoma are common after treatment cessation. Furthermore, a subset of infected individuals develop inflammation and are at greater risk for developing the severe sequela of trachoma known as trachomatous trichiasis (TT. While there are a number of environmental and behavioral risk factors for trachoma, genetic factors that influence inflammation and TT risk remain ill defined. METHODOLOGY/FINDINGS: We identified single nucleotide polymorphisms (SNP in 36 candidate inflammatory genes and interactions among these SNPs that likely play a role in the overall risk for TT. We conducted a case control study of 538 individuals of Tharu ethnicity residing in an endemic region of Nepal. Trachoma was graded according to World Health Organization guidelines. A linear array was used to genotype 51 biallelic SNPs in the 36 genes. Analyses were performed using logic regression modeling, which controls for multiple comparisons. We present, to our knowledge, the first significant association of TNFA (-308GA, LTA (252A, VCAM1 (-1594TC, and IL9 (T113M polymorphisms, synergistic SNPs and risk of TT. TT risk decreased 5 times [odds ratio = 0.2 (95% confidence interval 0.11.-0.33, p = 0.001] with the combination of TNFA (-308A, LTA (252A, VCAM1 (-1594C, SCYA 11 (23T minor allele, and the combination of TNFA (-308A, IL9 (113M, IL1B (5'UTR-T, and VCAM1 (-1594C. However, TT risk increased 13.5 times [odds ratio = 13.5 (95% confidence interval 3.3-22, p = 0.001] with the combination of TNFA (-308G, VDR (intron G, IL4R (50V, and ICAM1 (56M minor allele. CONCLUSIONS: Evaluating genetic risk factors for trachoma will advance our understanding of disease pathogenesis, and should

  10. 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.

  11. SEQUENCE POLYMORPHISMS OF FOUR CHLOROPLAST GENES IN FOUR ACACIA SPECIES

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    Anthonius Y.P.B.C. Widyatmoko

    2011-06-01

    Full Text Available Sequence polymorphisms among and within four Acacia species,  A. aulacocarpa, A. auriculiformis, A. crassicarpa, and A. mangium, were investigated using four chloroplast DNA genes (atpA, petA, rbcL, and rpoA. The phylogenetic relationship among these species is discussed in light of the results of the sequence information. No intraspecific sequence variation was found in the four genes of the four species, and a conservative rate of mutation of the chloroplast DNA genes was also confirmed in the Acacia species. In the atpA and petA of the four genes, all four species possessed identical sequences, and no sequence variation was found among the four Acacia species. In the rbcL and rpoA genes, however, sequence polymorphisms were revealed among these species. Acacia aulacocarpa and A. crassicarpa shared an identical sequence, and A. auriculiformis and A. mangium also showed no sequence variation.  The fact that A. mangium and A. auriculiformis shared identical sequences as did A. aulacocarpa and A. crassicarpa indicated that the two respective species were extremely closely related. Although a putative natural hybrid of A. aulacocarpa and A. auriculiformis has been reported, our results suggested that natural hybridization should be further verified using molecular markers.

  12. Polymorphism analysis of csd gene in six Apis mellifera subspecies.

    Science.gov (United States)

    Wang, Zilong; Liu, Zhiyong; Wu, Xiaobo; Yan, Weiyu; Zeng, Zhijiang

    2012-03-01

    The complementary sex determination (csd) gene is the primary gene determining the gender of honey bees (Apis spp). In this study we analyzed the polymorphism of csd gene in six Apis mellifera subspecies. The genomic region 3 of csd gene in these six A. mellifera was cloned, and identified. A total of 79 haplotypes were obtained from these six subspecies. Analysis showed that region 3 of csd gene has a high level of polymorphism in all the six A. mellifera subspecies. The A. m. anatolica subspecies has a slightly higher nucleotide diversity (π) than other subspecies, while the π values showed no significant difference among the other five subspecies. The phylogenetic tree showed that all the csd haplotypes from different A. mellifera subspecies are scattered throughout the tree, without forming six different clades. Population differentiation analysis showed that there are significant genetic differentiations among some of the subspecies. The NJ phylogenetic tree showed that the A. m. caucasica and A. m. carnica have the closest relationship, followed by A. m. ssp, A. m. ligustica, A. m. carpatica and A. m. anatolica that were gathered in the tree in turn.

  13. Polymorphism in ABC transporter genes of Dirofilaria immitis

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    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.

  14. Atlantic cod (Gadus morhua hemoglobin genes: multiplicity and polymorphism

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    Gamperl A Kurt

    2009-09-01

    Full Text Available Abstract Background Hemoglobin (Hb polymorphism, assessed by protein gel electrophoresis, has been used almost exclusively to characterize the genetic structure of Atlantic cod (Gadus morhua populations and to establish correlations with phenotypic traits such as Hb oxygen binding capacity, temperature tolerance and growth characteristics. The genetic system used to explain the results of gel electrophoresis entails the presence of one polymorphic locus with two major alleles (HbI-1; HbI-2. However, vertebrates have more than one gene encoding Hbs and recent studies have reported that more than one Hb gene is present in Atlantic cod. These observations prompted us to re-evaluate the number of Hb genes expressed in Atlantic cod, and to perform an in depth search for polymorphisms that might produce relevant phenotypes for breeding programs. Results Analysis of Expressed Sequence Tags (ESTs led to the identification of nine distinct Hb transcripts; four corresponding to the α Hb gene family and five to the β Hb gene family. To gain insights about the Hb genes encoding these transcripts, genomic sequence data was generated from heterozygous (HbI-1/2 parents and fifteen progeny; five of each HbI type, i.e., HbI-1/1, HbI-1/2 and HbI-2/2. β Hb genes displayed more polymorphism than α Hb genes. Two major allele types (β1A and β1B that differ by two linked non-synonymous substitutions (Met55Val and Lys62Ala were found in the β1 Hb gene, and the distribution of these β1A and β1B alleles among individuals was congruent with that of the HbI-1 and HbI-2 alleles determined by protein gel electrophoresis. RT-PCR and Q-PCR analysis of the nine Hb genes indicates that all genes are expressed in adult fish, but their level of expression varies greatly; higher expression of almost all Hb genes was found in individuals displaying the HbI-2/2 electrophoretic type. Conclusion This study indicates that more Hb genes are present and expressed in adult

  15. Research Related to Interleukin-4 Gene Polymorphism and Diabetes%白细胞介素-4基因多态性与糖尿病的相关研究进展

    Institute of Scientific and Technical Information of China (English)

    丁云飞; 孙曙光; 刘肖梅

    2015-01-01

    Diabetes is characterized by chronic hyperglycemia metabolic diseases. with the improvement of people's living standards, the aging population, the incidence rate was gradually rising trend. Diabetes pathogenesis is still not very clear so far, and pathogenesis of diabetes is now a hot topic. Interleukin-4 (IL-4) (10kb) located on chromosome 5q31.1, there are four polymorphic alleles. which has a strong linkage disequilibrium. In this paper, the correlation progress (IL-4) gene polymorphisms of interleukin-4 with type 1 diabetes, type 2 diabetes, diabetes complications start on.%糖尿病是慢性高血糖为特征的代谢性疾病。随着人民生活水平的提高、人口老化,发病率呈逐渐升高的流行趋势。糖尿病发病机制到目前仍不十分明确,糖尿病发病机制是现在的热点话题。白细胞介素-4(IL-4)(10 kb)位于染色体5q31.1上,有4个多态性的等位基因,它们具有很强的连锁不平衡。本文就白细胞介素-4(IL-4)基因多态性与1型糖尿病、2型糖尿病、糖尿病并发症的相关性进展展开论述。

  16. Correlation of interleukin-4 gene polymorphism with cerebral infarction%白细胞介素4基因多态性与脑梗死的关系

    Institute of Scientific and Technical Information of China (English)

    金磊; 陈宁; 吴洁敏; 张蕾; 徐志毅; 倪培华

    2015-01-01

    目的:探讨白细胞介素4(interleukin-4,IL-4)基因多态性与脑梗死间的相关性.方法:选取189例急性脑梗死患者(脑梗死组)和92例非急性脑梗死者(对照组),运用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)技术,结合血液生化和血压等临床资料,对 IL-4 基因-590C/T和33C/T 2个位点的基因单核苷酸多态性与脑梗死间的关系进行研究. 结果:IL-4基因-590C/T位点上,脑梗死组与对照组间的基因型、等位基因频率分布有显著差异(P0.05);脑梗死组TT型患者的收缩压、舒张压参数均明显高于对照组(P0.05) be-tween CI group and the control group. However, CI patients with TT genotype had higher blood pressure and lower HDL-C level (P<0.05) when compared with the control group. Conclusions: T allele of-590C/T polymorphism in IL-4 gene might be associated with an increased risk of CI in Shanghai population.

  17. Antibacterial properties of the mammalian L-amino acid oxidase IL4I1.

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    Marie-Line Puiffe

    Full Text Available L-amino acid oxidases (LAAO are flavoproteins that catalyze the oxidative deamination of L-amino acids to a keto-acid along with the production of H₂O₂ and ammonia. Interleukin 4 induced gene 1 (IL4I1 is a secreted LAAO expressed by macrophages and dendritic cells stimulated by microbial derived products or interferons, which is endowed with immunoregulatory properties. It is the first LAAO described in mammalian innate immune cells. In this work, we show that this enzyme blocks the in vitro and in vivo growth of Gram negative and Gram positive bacteria. This antibiotic effect is primarily mediated by H₂O₂ production but is amplified by basification of the medium due to the accumulation of ammonia. The depletion of phenylalanine (the primary amino acid catabolized by IL4I1 may also participate in the in vivo inhibition of staphylococci growth. Thus, IL4I1 plays a distinct role compared to other antibacterial enzymes produced by mononuclear phagocytes.

  18. NAM-1gene polymorphism and grain protein content in Hordeum.

    Science.gov (United States)

    Jamar, Catherine; Loffet, Francois; Frettinger, Patrick; Ramsay, Luke; Fauconnier, Marie-Laure; du Jardin, Patrick

    2010-04-15

    Grain protein content (GPC) is a key quality factor for malting and brewing process. In wheat, a QTL explaining a large part of GPC variation was identified, which co-localizes with a gene encoding a NAC transcription factor (TtNAM-B1). NAC transcription factors influence GPC by their role in the regulation of senescence and in protein remobilization. An orthologous gene was discovered on barley chromosome 6H where a GPC QTL was mapped. In this study, we identify allelic variation of the NAM-1 gene for three species of Hordeum representing wild and cultivated barley and we investigate the possible link with GPC. Three haplotypes were identified, one corresponds to the sequences of 11 European varieties representing H. vulgare, one corresponds to the sequence found in H. spontaneum and one represents the sequence of H. bulbosum. Three SNPs were identified between H. spontaneum sequence and H. vulgare sequence. One of the H. bulbosum polymorphisms leads to the introduction of a stop codon and a non-functional protein. Differences in GPC between the 11 varieties were found but no polymorphism in the NAM-1 gene was observed, suggesting that differences in expression of the HvNAM-1 gene or other genes should play a role in GPC regulation. Nevertheless based on published values for GPC of H. bulbosum and H. spontaneum compared to GPC measured here in H. vulgare, the non-functional protein is associated with the lower GPC, suggesting that loss of functionality of the NAM-1 gene in Hordeum is related to lower GPC. Moreover H. spontaneum GPC seems to be higher than H. vulgare GPC, suggesting also that allelic variation of the functional NAM-1 gene could be associated with GPC variation within the genus Hordeum. Copyright 2009 Elsevier GmbH. All rights reserved.

  19. Association of MMP-9 gene polymorphisms with nephrolithiasis patients.

    Science.gov (United States)

    Mehde, Atheer Awad; Mehdi, Wesen Adel; Yusof, Faridah; Raus, Raha Ahmed; Zainal Abidin, Zaima Azira; Ghazali, Hamid; Abd Rahman, Azlina

    2017-02-15

    Nephrolithiasis is one of the causes which lead to chronic kidney disease (CKD). Matrix metalloproteinases (MMPs) are endopeptidases degrading extracellular matrix which correlate with the pathogenesis of atherosclerosis. The current study was designed to analyze the association of (R279Q, C1562T) polymorphism of MMP-9 with nephrolithiasis patients. Genotyping of MMP-9/R279Q and of MMP-9/C1562T polymorphism were carried out by PCR-based restriction digestion method. Serum level of MMP-9, oxidative stress marker, MDA, and uric acid were measured in patients and control. Allele frequencies of the MMP-9/C1562T polymorphism for C and T allele were 71.25% and 28.75% in patients, 87.08% and 12.92% in control respectively. The homozygote TT was more frequent in the nephrolithiasis patients group, while T allele frequency was significantly higher in the nephrolithiasis patients group than in the control group. The patients with CT and TT genotype showed a significant increase in serum MMP-9, Total Oxidant Status (TOS), Oxidative Stress Index (OSI), Malondialdehyde (MDA), and uric acid when compared to CC genotype in patients with nephrolithiasis. The R279Q polymorphism site with regard to the relationship with nephrolithiasis was not significant. The result indicates that patients with TT genotype had an increased risk of stones. Also, the results demonstrate that TT allele of the C1562T polymorphism in the MMP-9gene is related with an increase of oxidative stress in nephrolithiasis patients and may possibly impose a risk for cardiovascular diseases in patients with TT genotype of MMP-9. © 2017 Wiley Periodicals, Inc.

  20. Association between interleukin-4 polymorphisms and asthma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To perform a systematic review and meta analysis on the association of C-589T and C-590T polymorphisms of IL-4 with asthma and to estimate allele frequencies, the magnitude of the gene effect as well as the possible mode of inheritance. Methods: A genetic model-free approach was used to perform a meta analysis. Heterogeneity, sensitivity analysis and publication bias were also explored. Results: Our meta analysis summarized the evidence to date regarding the association of C-589T and C-590T polymorphisms in the promoter region of IL-4 gene with asthma. For C-590T, the results showed a significant recessive genetic model, and the CC genotype was about 24% less likely to have asthma than the genotype CT and TT. Although there was evidence suggesting a recessive genetic model for C-589T, the recessive model was not statistically significant. Conclusion: This meta analysis suggests that there may be an important effect of single nucleotide polymorphisms (SNPs) in the promoter region of IL-4 gene on the pathogenesis of asthma.

  1. The relationship of host-mediated induced resistance to polymorphism in gene-for-gene relationships.

    Science.gov (United States)

    Tellier, Aurélien; Brown, James K M

    2008-01-01

    Gene-for-gene relationships are a common feature of plant-parasite interactions. Polymorphism at host resistance and parasite avirulence loci is maintained if there is negative, direct frequency-dependent selection on alleles of either gene. More specifically, selection of this kind is generated when the disease is polycyclic with frequent auto-infection. When an incompatible interaction occurs between a resistant host and an avirulent parasite, systemic defenses are triggered, rendering the plant more resistant to a later attack by another parasite. However, induced resistance (IR) incurs a fitness cost to the plant. Here, the effect of IR on polymorphism in gene-for-gene interactions is investigated. First, in an infinite population model in which parasites have two generations per host generation, increasing the fitness cost of IR increases selection for susceptible plants at low disease severity, while increasing the effectiveness of IR against further parasite attacks enhances selection for resistant plants at high disease severity. This reduces the possibility of polymorphism being maintained in host and parasite populations. In finite population models, the number of plants varies over time as a function of the disease burden of the population. Polymorphism in gene-for-gene relationships is then more stable at high disease prevalence and severity if IR reactions are more costly when there is competition for resources between plants.

  2. Polymorphisms in the leptin gene promoter in Brazilian beef herds.

    Science.gov (United States)

    Guimarães, R C; Azevedo, J S N; Corrêa, S C; Campelo, J E G; Barbosa, E M; Gonçalves, E C; Silva Filho, E

    2016-12-02

    Brazil is the world's largest producer of beef cattle; however, the quality of its herds needs to be improved. The use of molecular markers as auxiliary tools in selecting animals for reproduction with high pattern for beef production would significantly improve the quality of the final beef product in Brazil. The leptin gene has been demonstrated to be an excellent candidate gene for bovine breeding. The objective of this study was to sequence and compare the leptin gene promoter of Brazil's important cattle breeds in order to identify polymorphisms in it. Blood samples of the Nellore, Guzerat, Tabapuã, and Senepol breeds were collected for genomic DNA extraction. The genomic DNA was used as a template for polymerase chain reaction (PCR) to amplify a 1575-bp fragment, which in turn was sequenced, aligned, and compared between animals of different breeds. Twenty-three single nucleotide polymorphic sites, including transitions and transversions, were detected at positions -1457, -1452, -1446, -1397, -1392, -1361, -1238, -963,-901, -578, -516, -483, -478, -470, -432, -430, -292, -282, -272, -211, -202, -170, and -147. Additionally, two insertion sites at positions -680 and -416 and two deletion sites at positions -1255 and -1059 were detected. As the promoter region of the leptin gene has been demonstrated to vary among breeds, these variations must be tested for their use as potential molecular markers for artificial selection of animals for enhanced beef production in different systems of bovine production in Brazil.

  3. IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain.

    Science.gov (United States)

    Wang, H Y; Paul, W E; Keegan, A D

    1996-02-01

    IL-4 binds to a cell surface receptor complex that consists of the IL-4 binding protein (IL-4R alpha) and the gamma chain of the IL-2 receptor complex (gamma c). The receptors for IL-4 and IL-2 have several features in common; both use the gamma c as a receptor component, and both activate the Janus kinases JAK-1 and JAK-3. In spite of these similarities, IL-4 evokes specific responses, including the tyrosine phosphorylation of 4PS/IRS-2 and the induction of CD23. To determine whether sequences within the cytoplasmic domain of the IL-4R alpha specify these IL-4-specific responses, we transplanted the insulin IL-4 receptor motif (I4R motif) of the huIL-4R alpha to the cytoplasmic domain of a truncated IL-2R beta. In addition, we transplanted a region that contains peptide sequences shown to block Stat6 binding to DNA. We analyzed the ability of cells expressing these IL-2R-IL-4R chimeric constructs to respond to IL-2. We found that IL-4 function could be transplanted to the IL-2 receptor by these regions and that proliferative and differentiative functions can be induced by different receptor sequences.

  4. FTO gene polymorphisms and obesity risk: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Li Xiaobo

    2011-06-01

    Full Text Available Abstract Background The pathogenesis of obesity is reportedly related to variations in the fat mass and an obesity-associated gene (FTO; however, as the number of reports increases, particularly with respect to varying ethnicities, there is a need to determine more precisely the effect sizes in each ethnic group. In addition, some reports have claimed ethnic-specific associations with alternative SNPs, and to that end there has been a degree of confusion. Methods We searched PubMed, MEDLINE, Web of Science, EMBASE, and BIOSIS Preview to identify studies investigating the associations between the five polymorphisms and obesity risk. Individual study odds ratios (OR and their 95% confidence intervals (CI were estimated using per-allele comparison. Summary ORs were estimated using a random effects model. Results We identified 59 eligible case-control studies in 27 articles, investigating 41,734 obesity cases and 69,837 healthy controls. Significant associations were detected between obesity risk and the five polymorphisms: rs9939609 (OR: 1.31, 95% CI: 1.26 to 1.36, rs1421085 (OR: 1.43, 95% CI: 1.33 to 1.53, rs8050136 (OR: 1.25, 95% CI: 1.13 to 1.38, rs17817449 (OR: 1.54, 95% CI: 1.41 to 1.68, and rs1121980 (OR: 1.34, 95% CI: 1.10 to 1.62. Begg's and Egger's tests provided no evidence of publication bias for the polymorphisms except rs1121980. There is evidence of higher heterogeneity, with I2 test values ranging from 38.1% to 84.5%. Conclusions This meta-analysis suggests that FTO may represent a low-penetrance susceptible gene for obesity risk. Individual studies with large sample size are needed to further evaluate the associations between the polymorphisms and obesity risk in various ethnic populations.

  5. IL-4Rα-dependent alternative activation of macrophages is not decisive for Mycobacterium tuberculosis pathology and bacterial burden in mice.

    Directory of Open Access Journals (Sweden)

    Reto Guler

    Full Text Available Classical activation of macrophages (caMph or M1 is crucial for host protection against Mycobacterium tuberculosis (Mtb infection. Evidence suggests that IL-4/IL-13 alternatively activated macrophages (aaMph or M2 are exploited by Mtb to divert microbicidal functions of caMph. To define the functions of M2 macrophages during tuberculosis (TB, we infected mice deficient for IL-4 receptor α on macrophages (LysMcreIL-4Rα-/lox with Mtb. We show that absence of IL-4Rα on macrophages does not play a major role during infection with Mtb H37Rv, or the clinical Beijing strain HN878. This was demonstrated by similar mortality, bacterial burden, histopathology and T cell proliferation between infected wild-type (WT and LysMcreIL-4Rα-/lox mice. Interestingly, we observed no differences in the lung expression of inducible nitric oxide synthase (iNOS and Arginase 1 (Arg1, well-established markers for M1/M2 macrophages among the Mtb-infected groups. Kinetic expression studies of IL-4/IL-13 activated bone marrow-derived macrophages (BMDM infected with HN878, followed by gene set enrichment analysis, revealed that the MyD88 and IL-6, IL-10, G-CSF pathways are significantly enriched, but not the IL-4Rα driven pathway. Together, these results suggest that IL-4Rα-macrophages do not play a central role in TB disease progression.

  6. Genetic polymorphisms located in genes related to immune and inflammatory processes are associated with end-stage renal disease: a preliminary study

    Directory of Open Access Journals (Sweden)

    Jimenez-Sousa Ma

    2012-07-01

    Full Text Available Abstract Background Chronic kidney disease progression has been linked to pro-inflammatory cytokines and markers of inflammation. These markers are also elevated in end-stage renal disease (ESRD, which constitutes a serious public health problem. Objective To investigate whether single nucleotide polymorphisms (SNPs located in genes related to immune and inflammatory processes, could be associated with ESRD development. Design and methods A retrospective case-control study was carried out on 276 patients with ESRD and 288 control subjects. Forty-eight SNPs were genotyped via SNPlex platform. Logistic regression was used to assess the relationship between each sigle polymorphism and the development of ESRD. Results Four polymorphisms showed association with ESRD: rs1801275 in the interleukin 4 receptor (IL4R gene (OR: 0.66 (95%CI = 0.46-0.95; p = 0.025; overdominant model, rs4586 in chemokine (C-C motif ligand 2 (CCL2 gene (OR: 0.70 (95%CI = 0.54-0.90; p = 0.005; additive model, rs301640 located in an intergenic binding site for signal transducer and activator of transcription 4 (STAT4 (OR: 1.82 (95%CI = 1.17-2.83; p = 0.006; additive model and rs7830 in the nitric oxide synthase 3 (NOS3 gene (OR: 1.31 (95%CI = 1.01-1.71; p = 0.043; additive model. After adjusting for multiple testing, results lost significance. Conclusion Our preliminary data suggest that four genetic polymorphisms located in genes related to inflammation and immune processes could help to predict the risk of developing ESRD.

  7. Hindiii and S447x polymorphisms of lipoprotein lipase gene and ...

    African Journals Online (AJOL)

    Hindiii and S447x polymorphisms of lipoprotein lipase gene and their relationship to coronary artery disease. ... Lipoprotein lipase is a key enzyme in lipoprotein metabolism and its gene is a major candidate gene for coronary ... Article Metrics.

  8. 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 (Cock)

    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

  9. Angiotensin converting enzyme gene polymorphism in familial hypertrophic cardiomyopathy patients

    Energy Technology Data Exchange (ETDEWEB)

    Yu, B; Peric, S.; Ross, D. [Royal Prince Alfred Hospital, Campertown (Australia)] [and others

    1994-09-01

    An insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene is a useful predictor of human plasma ACE levels. ACE levels tend to be lowest in subjects with ACE genotype DD and intermediate in subjects with ACE genotype ID. Angiotensin II (Ang II) as a product of ACE is a cardiac growth factor and produces a marked hypertrophy of the chick myocyte in cell culture. Rat experiments also suggest that a small dose of ACE inhibitor that does not affect the afterload results in prevention or regression of cardiac hypertrophy. In order to study the relationship of ACE and the severity of hypertrophy, the ACE genotype has been determined in 28 patients with a clinical diagnosis of familial hypertrophic cardiomyopathy (FHC) and 51 normal subjects. The respective frequencies of I and D alleles were: 0.52 and 0.48 (in FHC patients) and 0.44 and 0.56 (in the normal controls). There was no significant difference in the allele frequencies between FHC and normal subjects ({chi}{sup 2}=0.023, p>0.05). The II, ID, and DD genotypes were present in 7, 15, and 6 FHC patients, respectively. The averages of maximal thickness of the interventricular septum measured by echocardiography or at autopsy were 18 {plus_minus}3, 19{plus_minus}4, and 19{plus_minus}3 mm in II, ID and DD genotypes, respectively. The ACE gene polymorphism did not correlate with the severity of left ventricular hypertrophy in FHC patients (r{sub s}=0.231, p>0.05). These results do not necessarily exclude the possible effect of Ang II on the hypertrophy since the latter may be produced through the action of chymase in the human ventricles. However, ACE gene polymorphism is not a useful predictor of the severity of myocardial hypertrophy in FHC patients.

  10. BDKRB2 GENE -9/+9 POLYMORPHISM AND SWIMMING PERFORMANCE

    Directory of Open Access Journals (Sweden)

    A. Grenda

    2014-07-01

    Full Text Available The aim of the study was to evaluate the association between swimming performance and the -9/+9 (rs5810761 polymorphism within the BDKRB2 gene in successful competitive swimmers.Best individual swimming results expressed in FINA points achieved at short, middle and long distance events of 157 well-trained Polish swimmers were incorporated into an analysis. Athletes’ genotype and allele distributions were analysed in comparison to 230 unrelated sedentary subjects who served as controls with the χ2 test. All samples were genotyped for the BDKRB2 -9/+9 polymorphism using the polymerase chain reaction (PCR. The effects of genotype on swimming performance were analysed with two-way (3 x 2; genotype x gender analysis of variance with metrical age as a covariate for each distance specialization. No statistical differences in the genotype and allele frequencies were found in long distance swimmers when compared with the total group of swimmers or controls. The BDKRB2 +9/-9 genotype had no significant effect on swimming performance at short, middle or long distance, regardless of gender. The results of this study do not support the hypothesis that the BDKRB2 -9/+9 polymorphism is associated with swimming performance in Polish swimmers.

  11. Polymorphisms in inflammatory genes, plasma antioxidants, and prostate cancer risk

    Science.gov (United States)

    Zhang, Jianjun; Dhakal, Ishwori B.; Lang, Nicholas P.; Kadlubar, Fred F.

    2011-01-01

    Background Presence of xenotropic murine leukemia virus–related virus and chronic inflammation in prostate tumor suggests that inflammation plays a role in prostate cancer etiology. This study investigated whether variants in inflammatory genes act alone or interact with plasma antioxidants to influence prostate cancer risk in a population-based case-control study in Central Arkansas. Methods Cases (n = 193) were men, aged 40–80, diagnosed with prostate cancer in three major hospitals in 1998–2003, and controls (n = 197) were matched to cases by age, race, and county of residence. Results After adjustment for confounders, polymorphisms in COX-2 (rs689466) and IL-8 (rs4073) were not significantly associated with prostate cancer risk. However, apparent interactions were observed between these genetic variants and plasma antioxidants on the risk of this malignancy. The protective effect of the mutant allele of the COX-2 polymorphism was more pronounced among subjects with high plasma levels of β-cryptoxanthin, lycopene, β-carotene, or selenium (≥median) [e.g., OR (95% CI): 0.37 (0.15, 0.86) (AG/GG vs. AA) for β-cryptoxanthin]. Conversely, the promoting effect of the variant allele of the IL-8 polymorphism was more remarkable in subjects with low plasma levels of Lutein/zeaxanthin, β-cryptoxanthin, and β-carotene (antioxidants to modulate prostate cancer risk. PMID:20431935

  12. Polymorphisms in cyclooxygenase-2 gene in endometrial cancer patients.

    Science.gov (United States)

    Torricelli, Federica; Mandato, Vincenzo Dario; Farnetti, Enrico; Abrate, Martino; Casali, Bruno; Ciarlini, Gino; Pirillo, Debora; Gelli, Maria Carolina; Costagliola, Luigi; Nicoli, Davide; Palomba, Stefano; La Sala, Giovanni Battista

    2015-09-01

    The enzyme cyclooxygenase 2 is an inducible enzyme expressed at sites of inflammation and in a variety of malignant solid tumors such as endometrial cancer (EC). In EC patients, its over-expression is correlated with progressive disease and poor prognosis. The expression is encoded by a polymorphic gene, called PTGS2. The aim of the current study was to test the hypothesis that rs5275 polymorphism of PTGS2 influence the prognosis of EC patients. This paper is a retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumor tissues. A total of 159 type I EC patients were included in the final analysis. Univariate analysis indicated that patients with rs5275 genotype CC have a lower risk to develop a grade (G) 2-3 endometrial cancer. rs5275 effect on EC grading was confirmed by multivariate analysis also after data adjusting for age, BMI, parity, hypertension, and diabetes. Adjusted odds ratio (OR) confirmed that patients with rs5275 genotype CC have a risk 80 % lower (OR = 0.20, P = 0.009) to develop a G2 and/or G3 EC in comparison with patients with TT or TC genotype. Differentiation of the type 1 EC is significantly and independently influenced by rs5275 polymorphism. rs5275 CC patients have a lower risk to present a G2-G3 EC.

  13. Polymorphisms in genes involved in neurotransmission in relation to smoking.

    Science.gov (United States)

    Arinami, T; Ishiguro, H; Onaivi, E S

    2000-12-27

    Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D(1), D(2), and D(4) receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D(3) and D(5) receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.

  14. Unique nucleotide polymorphism of ankyrin gene cluster in Arabidopsis

    Indian Academy of Sciences (India)

    Jianchang Du; Xingna Wang; Mingsheng Zhang; Dacheng Tian; Yong-Hua Yang

    2007-01-01

    The ankyrin (ANK) gene cluster is a part of a multigene family encoding ANK transmembrane proteins in Arabidopsis thaliana, and plays an important role in protein–protein interactions and in signal pathways. In contrast to other regions of a genome, the ANK gene cluster exhibits an extremely high level of DNA polymorphism in an ∼5-kb region, without apparent decay. Phylogenetic analysis detects two clear, deeply differentiated haplotypes (dimorphism). The divergence between haplotypes of accession Col-0 and Ler-0 (Hap-C and Hap-L) is estimated to be 10.7%, approximately equal to the 10.5% average divergence between A. thaliana and A. lyrata. Sequence comparisons for the ANK gene cluster homologues in Col-0 indicate that the members evolve independently, and that the similarity among paralogues is lower than between alleles. Very little intralocus recombination or gene conversion is detected in ANK regions. All these characteristics of the ANK gene cluster are consistent with a tandem gene duplication and birth-and-death process. The possible mechanisms for and implications of this elevated nucleotide variation are also discussed, including the suggestion of balancing selection.

  15. Polymorphisms in Endothelin System Genes, Arsenic Levels and Obesity Risk

    Science.gov (United States)

    Martínez-Barquero, Vanesa; de Marco, Griselda; Martínez-Hervas, Sergio; Rentero, Pilar; Galan-Chilet, Inmaculada; Blesa, Sebastian; Morchon, David; Morcillo, Sonsoles; Rojo, Gemma; Ascaso, Juan Francisco; Real, José Tomás; Martín-Escudero, Juan Carlos; Chaves, Felipe Javier

    2015-01-01

    Background/Objectives Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity. Subjects/Methods We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex. Results We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63) and in the Hortega sample (p=0.001, OR=0.62). Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66) and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70). Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively). Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51) and rs3759475 (p=0.009, OR=0.53) Conclusions Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to

  16. Polymorphisms in endothelin system genes, arsenic levels and obesity risk.

    Directory of Open Access Journals (Sweden)

    Vanesa Martínez-Barquero

    Full Text Available Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs in the EDN system could be associated with human obesity.We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex.We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63 and in the Hortega sample (p=0.001, OR=0.62. Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66 and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70. Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively. Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51 and rs3759475 (p=0.009, OR=0.53.Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to obesity and can interact with plasma arsenic

  17. Polymorphisms in endothelin system genes, arsenic levels and obesity risk.

    Science.gov (United States)

    Martínez-Barquero, Vanesa; de Marco, Griselda; Martínez-Hervas, Sergio; Rentero, Pilar; Galan-Chilet, Inmaculada; Blesa, Sebastian; Morchon, David; Morcillo, Sonsoles; Rojo, Gemma; Ascaso, Juan Francisco; Real, José Tomás; Martín-Escudero, Juan Carlos; Chaves, Felipe Javier

    2015-01-01

    Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity. We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex. We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63) and in the Hortega sample (p=0.001, OR=0.62). Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66) and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70). Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively). Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51) and rs3759475 (p=0.009, OR=0.53). Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to obesity and can interact with plasma arsenic levels.

  18. Bovine gene polymorphisms related to fat deposition and meat tenderness

    Directory of Open Access Journals (Sweden)

    Marina R.S. Fortes

    2009-01-01

    Full Text Available Leptin, thyroglobulin and diacylglycerol O-acyltransferase play important roles in fat metabolism. Fat deposition has an influence on meat quality and consumers' choice. The aim of this study was to determine allele and genotype frequencies of polymorphisms of the bovine genes, which encode leptin (LEP, thyroglobulin (TG and diacylglycerol O-acyltransferase (DGAT1. A further objective was to establish the effects of these polymorphisms on meat characteristics. We genotyped 147 animals belonging to the Nelore (Bos indicus, Canchim (5/8 Bos taurus + 3/8 Bos indicus, Rubia Gallega X Nelore (1/2 Bos taurus + 1/2 Bos indicus, Brangus Three-way cross (9/16 Bos taurus + 7/16 Bos indicus and Braunvieh Three-way cross (3/4 Bos taurus + 1/4 Bos indicus breeds. Backfat thickness, total lipids, marbling score, ribeye area and shear force were fitted, using the General Linear Model (GLM procedure of the SAS software. The least square means of genotypes and genetic groups were compared using Tukey's test. Allele frequencies vary among the genetic groups, depending on Bos indicus versus Bos taurus influence. The LEP polymorphism segregates in pure Bos indicus Nelore animals, which is a new finding. The T allele of TG is fixed in Nelore, and DGAT1 segregates in all groups, but the frequency of allele A is lower in Nelore animals. The results showed no association between the genotypes and traits studied, but a genetic group effect on these traits was found. So, the genetic background remains relevant for fat deposition and meat tenderness, but the gene markers developed for Bos taurus may be insufficient for Bos indicus.

  19. THE ASSOCIATION OF GENE POLYMORPHISMS WITH ATHLETE STATUS IN UKRAINIANS

    Science.gov (United States)

    Dosenko, V.E.; Ahmetov, I.I.; Ilyin, V.N.

    2013-01-01

    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. 9.4%, P = 0.034) and NOS3 T alleles (78.3 vs. 66.2%, P = 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. 13.5%; P = 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. PMID:24744483

  20. Association between polymorphisms in the TSHR gene and Graves' orbitopathy.

    Directory of Open Access Journals (Sweden)

    Beata Jurecka-Lubieniecka

    Full Text Available BACKGROUND: Graves' orbitopathy (GO as well as Graves' disease (GD hyperthyroidism originate from an autoimmune reaction against the common auto-antigen, thyroid-stimulating hormone receptor (TSHR. GO phenotype is associated with environmental risk factors, mainly nicotinism, as well as genetic risk factors which initiate an immunologic reaction. In some patients GO is observed before diagnosis of GD hyperthyroidism, while it can also be observed far after diagnosis. The intensity of GO symptoms varies greatly in these patients. Thus, the pathogenesis of GD and GO may correlate with different genetic backgrounds, which has been confirmed by studies of correlations between GO and polymorphisms in cytokines involved in orbit inflammation. The aim of our analysis was to assess genetic predisposition to GO in young patients (age of diagnosis ≤30 years of age, for whom environmental effects had less time to influence outcomes than in adults. METHODS: 768 GD patients were included in the study. 359 of them had clinically evident orbitopathy (NOSPECS ≥2. Patients were stratified by age at diagnosis. Association analyses were performed for genes with a known influence on development of GD - TSHR, HLA-DRB1, cytotoxic T-lymphocyte antigen 4 (CTLA4 and lymphoid protein tyrosine phosphatase (PTPN22. RESULTS: The rs179247 TSHR polymorphism was associated with GO in young patients only. In young GO-free patients, allele A was statistically more frequent and homozygous carriers had a considerable lower risk of disease incidence than patients with AG or GG genotypes. Those differences were not found in either elderly patients or the group analyzed as a whole. CONCLUSIONS: Allele A of the rs179247 polymorphism in the TSHR gene is associated with lower risk of GO in young GD patients.

  1. THE ASSOCIATION OF GENE POLYMORPHISMS WITH ATHLETE STATUS IN UKRAINIANS

    Directory of Open Access Journals (Sweden)

    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.

  2. Sequencing genes in silico using single nucleotide polymorphisms

    Directory of Open Access Journals (Sweden)

    Zhang Xinyi

    2012-01-01

    Full Text Available Abstract Background The advent of high throughput sequencing technology has enabled the 1000 Genomes Project Pilot 3 to generate complete sequence data for more than 906 genes and 8,140 exons representing 697 subjects. The 1000 Genomes database provides a critical opportunity for further interpreting disease associations with single nucleotide polymorphisms (SNPs discovered from genetic association studies. Currently, direct sequencing of candidate genes or regions on a large number of subjects remains both cost- and time-prohibitive. Results To accelerate the translation from discovery to functional studies, we propose an in silico gene sequencing method (ISS, which predicts phased sequences of intragenic regions, using SNPs. The key underlying idea of our method is to infer diploid sequences (a pair of phased sequences/alleles at every functional locus utilizing the deep sequencing data from the 1000 Genomes Project and SNP data from the HapMap Project, and to build prediction models using flanking SNPs. Using this method, we have developed a database of prediction models for 611 known genes. Sequence prediction accuracy for these genes is 96.26% on average (ranges 79%-100%. This database of prediction models can be enhanced and scaled up to include new genes as the 1000 Genomes Project sequences additional genes on additional individuals. Applying our predictive model for the KCNJ11 gene to the Wellcome Trust Case Control Consortium (WTCCC Type 2 diabetes cohort, we demonstrate how the prediction of phased sequences inferred from GWAS SNP genotype data can be used to facilitate interpretation and identify a probable functional mechanism such as protein changes. Conclusions Prior to the general availability of routine sequencing of all subjects, the ISS method proposed here provides a time- and cost-effective approach to broadening the characterization of disease associated SNPs and regions, and facilitating the prioritization of candidate

  3. Polymorphism of the human vitronectin gene causes vitronectin blood type.

    Science.gov (United States)

    Kubota, K; Hayashi, M; Oishi, N; Sakaki, Y

    1990-03-30

    Human blood plasma/sera are classified into three distinct vitronectin types based on the relative amount of the 75 kDa polypeptide to its cleavage product of 65 kDa. We asked whether the vitronectin blood types correlated with the polymorphism of the vitronectin gene. A portion of the vitronectin gene was amplified by using polymerase chain reaction and digested with a restriction enzyme PmaC I which may distinguish the base sequence causing the polymorphic change at the amino acid position 381. Amplified DNAs of the blood type I (75 kDa-rich), II (75/65 kDa-even), and III (65 kDa-rich) were shown to be resistant, moderately sensitive and completely sensitive to PmaC I, respectively. These results suggest that Thr at position 381 is essential for the cleavage of the vitronectin 75 kDa polypeptide and that three possible combinations of two codominant alleles of vitronectin determine three vitronectin blood types.

  4. CYP2A6 gene polymorphisms impact to nicotine metabolism

    Directory of Open Access Journals (Sweden)

    Dewi Muliaty

    2010-02-01

    Full Text Available Nicotine is a major addictive compound in tobacco cigarette smoke. After being absorbed by the lung nicotine is rapidly metabolized and mainly inactivated to cotinine by hepatic cytochrome P450 2A6 (CYP2A6 enzyme. Genetic polymorphisms in CYP2A6 may play a role in smoking behavior and nicotine dependence. CYP2A6*1A is the wild type of the CYP2A6 gene which is associated with normal or extensive nicotine metabolism. In the CYP2A6 gene, several polymorphic alleles have been reported such as CYP2A6*4, CYP2A6*7, CYP2A6*9, and CYP2A6*10 which are related to decreasing nicotine metabolism activity. The variation of nicotine metabolism activity could alter nicotine plasma levels. Smokers need a certain level of nicotine in their brain and must smoke regularly because of nicotine’s short half-life; this increases the number of smoked cigarettes in extensive metabolizers. Meanwhile, in slow metabolizers, nicotine plasma level may increase and results in nicotine toxicity. This will eventually lower the risk of dependence. (Med J Indones 2010; 19:46-51Keywords: cotinine, hepatic cytochrome P450 2A6, smoking behavior

  5. Population stratification of a common APOBEC gene deletion polymorphism.

    Directory of Open Access Journals (Sweden)

    Jeffrey M Kidd

    2007-04-01

    Full Text Available The APOBEC3 gene family plays a role in innate cellular immunity inhibiting retroviral infection, hepatitis B virus propagation, and the retrotransposition of endogenous elements. We present a detailed sequence and population genetic analysis of a 29.5-kb common human deletion polymorphism that removes the APOBEC3B gene. We developed a PCR-based genotyping assay, characterized 1,277 human diversity samples, and found that the frequency of the deletion allele varies significantly among major continental groups (global FST = 0.2843. The deletion is rare in Africans and Europeans (frequency of 0.9% and 6%, more common in East Asians and Amerindians (36.9% and 57.7%, and almost fixed in Oceanic populations (92.9%. Despite a worldwide frequency of 22.5%, analysis of data from the International HapMap Project reveals that no single existing tag single nucleotide polymorphism may serve as a surrogate for the deletion variant, emphasizing that without careful analysis its phenotypic impact may be overlooked in association studies. Application of haplotype-based tests for selection revealed potential pitfalls in the direct application of existing methods to the analysis of genomic structural variation. These data emphasize the importance of directly genotyping structural variation in association studies and of accurately resolving variant breakpoints before proceeding with more detailed population-genetic analysis.

  6. The role of ERBB2 gene polymorphisms in leprosy susceptibility

    Directory of Open Access Journals (Sweden)

    Jamile Leão Rêgo

    Full Text Available Mycobacterium leprae infects skin and peripheral nerves causing deformities and disability. The M. leprae bacterium binds to ErbB2 on the Schwann cell surface causing demyelination and favoring spread of the bacilli and causing nerve injury. Polymorphisms at the ERBB2 gene were previously investigated as genetic risk factors for leprosy in two Brazilian populations but with inconsistent results. Herein we extend the analysis of ERBB2 variants to a third geographically distinct population in Brazil. Our results show that there is no association between the genotyped SNPs and the disease (p > 0.05 in this population. A gene set or pathway analysis under the genomic region of ERBB2 will be necessary to clarify its regulation under M. leprae stimulus.

  7. IL4I1 Is a Novel Regulator of M2 Macrophage Polarization That Can Inhibit T Cell Activation via L-Tryptophan and Arginine Depletion and IL-10 Production.

    Directory of Open Access Journals (Sweden)

    Yinpu Yue

    Full Text Available Interleukin 4-induced gene-1 (IL4I1 was initially described as an early IL-4-inducible gene in B cells. IL4I1 protein can inhibit T cell proliferation by releasing its enzymatic catabolite, H2O2, and this effect is associated with transient down-regulation of T cell CD3 receptor-zeta (TCRζ expression. Herein, we show that IL4I1 contributes to the regulation of macrophage programming. We found that expression of IL4I1 increased during bone marrow-derived macrophage (BMDM differentiation, expression of IL4I1 is much higher in primary macrophages than monocytes, and IL4I1 expression in BMDMs could be induced by Th1 and Th2 cytokines in two different patterns. Gene expression analysis revealed that overexpression of IL4I1 drove the expression of M2 markers (Fizz1, Arg1, YM-1, MR and inhibited the expression of M1-associated cytokines. Conversely, knockdown of IL4I1 by siRNA resulted in opposite effects, and also attenuated STAT-3 and STAT-6 phosphorylation. Furthermore, IL4I1 produced by macrophages catalyzed L-tryptophan degradation, while levo-1-methyl-tryptophan (L-1-MT, but not dextro-1-methyl-tryptophan, partially rescued IL4I1-dependent inhibition of T cell activation. Other inhibitors, such as diphenylene iodonium (DPI, an anti-IL-10Rα blocking antibody, and a nitric oxide synthase inhibitor, NG-monomethyl-L-arginine, also had this effect. Overall, our findings indicate that IL4I1 promotes an enhanced M2 functional phenotype, which is most likely associated with the phosphorylation of STAT-6 and STAT-3. Moreover, DPI, L-1-MT, NG-monomethyl-L-arginine, and anti-IL-10Rα blocking antibody were all found to be effective IL4I1 inhibitors in vitro.

  8. Phosphodiesterase 4D gene polymorphisms in sudden sensorineural hearing loss.

    Science.gov (United States)

    Chien, Chen-Yu; Tai, Shu-Yu; Wang, Ling-Feng; Hsi, Edward; Chang, Ning-Chia; Wang, Hsun-Mo; Wu, Ming-Tsang; Ho, Kuen-Yao

    2016-09-01

    The phosphodiesterase 4D (PDE4D) gene has been reported as a risk gene for ischemic stroke. The vascular factors are between the hypothesized etiologies of sudden sensorineural hearing loss (SSNHL), and this genetic effect might be attributed for its role in SSNHL. We hypothesized that genetic variants of the PDE4D gene are associated with susceptibility to SSNHL. We conducted a case-control study with 362 SSNHL cases and 209 controls. Three single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. We carried out sex-specific analysis to analyze the overall data. All three SNPs were in HWE. When subjects were stratified by sex, the genetic effect was only evident in females but not in males. The TT genotype of rs702553 exhibited an adjusted odds ratio (OR) of 3.83 (95 % confidence interval = 1.46-11.18) (p = 0.006) in female SSNHL. The TT genotype of SNP rs702553 was associated with female SSNHL under the recessive model (p = 0.004, OR 3.70). In multivariate logistic regression analysis, TT genotype of rs702553 was significantly associated with female SSNHL (p = 0.0043, OR 3.70). These results suggest that PDE4D gene polymorphisms influence the susceptibility for the development of SSNHL in the southern Taiwanese female population.

  9. Association of VMAT2 gene polymorphisms with alcohol dependence.

    Science.gov (United States)

    Fehr, Christoph; Sommerlad, Daniel; Sander, Thomas; Anghelescu, Ion; Dahmen, Norbert; Szegedi, Armin; Mueller, Christiana; Zill, Peter; Soyka, Michael; Preuss, Ulrich W

    2013-08-01

    Alcohol-related diseases cause significant harm in the western world. Up to 65 % of the phenotypic variance is genetically determined. Few candidate genes have been identified, comprising ADH4, ALDH2, COMT, CRHR1, DAT (SLC6A3), GABRA2 and MAOA. While abnormalities in the dopaminergic mesolimbic reward system are considered important mediators of alcoholism, studies analyzing variants of dopamine receptors showed conflicting results. Other modulators of the reward system are synaptosomal genes. Among candidate genes, polygenic variants of the Vesicular Monamine Transporter 2 (VMAT2) gene locus associated with alterations of drinking behavior were published. These variants comprise single nucleotide polymorphisms (SNPs) within the promoter region and the open reading frame. In this study, we confirm the association of VMAT2 SNP rs363387 (allelic association: p = 0.015) with alcohol dependence. This SNP defines several haplotypes including up to four SNPs (minimal p = 0.0045). In addition, numeric effects in the subgroups of males and patients with positive family history were found. We suggest that several rs363387 T-allele containing haplotypes increase the risk of alcohol dependence (OR 1.53), whereas G-allele containing haplotypes confer protection against alcohol dependence. Taken together, there is supporting evidence for a contribution of VMAT2 gene variants to phenotypes of alcohol dependence.

  10. CXC motif chemokine receptor 4 gene polymorphism and cancer risk

    Science.gov (United States)

    Wu, Yang; Zhang, Chun; Xu, Weizhang; Zhang, Jianzhong; Zheng, Yuxiao; Lu, Zipeng; Liu, Dongfang; Jiang, Kuirong

    2016-01-01

    Abstract Background: Previous epidemiological studies have reported the relationship between CXC motif chemokine receptor 4 (CXCR4) synonymous polymorphism (rs2228014), and risk of cancer, but the results remained conflicting and controversial. Therefore, this study was devised to evaluate the genetic effects of the rs2228014 polymorphism on cancer risk in a large meta-analysis. Methods: The computer-based databases (EMBASE, Web of Science, and PubMed) were searched for all relevant studies evaluating rs2228014 and susceptibility to cancer. In the analysis, pooled odds ratios (ORs) with its corresponding 95% confidence intervals (CIs) were calculated in 5 genetic models to assess the genetic risk. Egger regression and Begg funnel plots test were conducted to appraise the publication bias. Results: Data on rs2228014 polymorphism and overall cancer risk were available for 3684 cancer patients and 5114 healthy controls participating in 11 studies. Overall, a significantly increased risk of cancer was associated with rs2228014 polymorphism in homozygote model (OR = 2.01, 95% CI: 1.22–3.33) and in recessive model (OR = 1.97, 95% CI: 1.23–3.16). When stratified by ethnicity, the results were positive only in Asian populations (heterozygote model: OR = 1.36, 95% CI: 1.13–1.65; homozygote model: OR = 2.43, 95% CI: 1.21–4.91; dominant model: OR = 1.47, 95% CI: 1.13–1.90; recessive model: OR = 2.25, 95% CI: 1.13–4.48; and allele model: OR = 1.48, 95% CI: 1.10–1.99). Besides, in the subgroup analysis by source of control, the result was significant only in population-based control (homozygote model: OR = 2.39, 95% CI: 1.06–5.40; recessive model: pooled OR = 2.24, 95% CI: 1.02–4.96). Conclusion: In general, our results first indicated that the rs2228014 polymorphism in CXCR4 gene is correlated with an increased risk of cancer, especially among Asian ethnicity. Large, well-designed epidemiological studies are required to verify the current findings. PMID

  11. Poly (ADP-ribose) polymerase-1 gene polymorphism in various Chinese nationalities

    Institute of Scientific and Technical Information of China (English)

    Hairong Liang; Junli Shao; Yuting Gao; Linhua Liu; Juanxiu Dai; Yun He; Huanwen Tang

    2011-01-01

    Poly (ADP-ribose) polymerase-1 (PARP-1) can exacerbate ischemic brain injury and lessen ischemic neuronal death, which may be associated with PARP-1 polymorphisms. The present study investigated human PARP-1 gene polymorphisms in various Chinese nationalities, the results of which could potentially help in the treatment and prevention of neurologic diseases. Genetic polymorphisms of seven exons in the PARP-1 gene, in 898 Chinese Han, Buyi, Shui, Miao, and Zhuang subjects, were investigated by PCR-single-strand conformation polymorphism. A single-strand conformation polymorphism variant in exons 12, 13, 16, and 17 of the PARP-1 gene was identified in 148 people, with two stationary bands showing three degenerative single strands.Results showed that the PARP-1 gene polymorphisms exist in various nationalities, and may act as a biomarker for susceptibility to disease.

  12. IL-4 regulates susceptibility to intestinal inflammation in murine food allergy

    National Research Council Canada - National Science Library

    Cristina R. Cardoso; Pauline R. Provinciatto; Dannielle F. Godoi; Beatriz R. Ferreira; Gerlinde Teixeira; Marcos A. Rossi; Fernando Q. Cunha; João S. Silva

    2009-01-01

    ... observed in food allergy. Accordingly, this work aimed to study the role of Th2/IL-4-dependent responses in the development of food allergy and intestinal pathology. C57BL/6 wild-type (WT) and IL-4...

  13. Polymorphism of regulators of apoptosis and growth factors genes in chronic lymphatic leukemia

    Directory of Open Access Journals (Sweden)

    Viktorova T.V.

    2011-12-01

    Full Text Available The objective of the research is to study the role of polymorphic variants of Tumor Necrosis Factor (TNF — a (TNFA, Bcl2-associated X protein (BAX p53-Binding Protein (MDM2, vascular endothelial growth factor (VEGFA and basic fibroblast growth factor (bFGF genes in chronic lymphocytic leukemia (CLL. Methods: The comparative analysis of alleles and genotypes distributions in CLL patients (N=133 and healthy individuals (N=196 from Bashkortostan Republic has been carried out. Results: Analysis of the distribution frequency of genotypes and alleles of the genes studied has showed an increase in frequency of genotypes GG and allele G polymorphic locus-308G> A TNFA gene, GG and allele G of the polymorphic locus-248G>A BAX gene, allele G of the polymorphic locus 309T> G gene MDM2 and allele С polymorphic locus 773C>T bFGF gene in patients with CLL

  14. Immune regulatory gene polymorphisms as predisposing risk factors for the development of factor VIII inhibitors in Indian severe haemophilia A patients.

    Science.gov (United States)

    Pinto, P; Ghosh, K; Shetty, S

    2012-09-01

    Development of inhibitors to factor VIII, a serious complication of replacement therapy in haemophilia A patients, leads to increased bleeding, morbidity and mortality. There is no data on the risk factors for inhibitor development in Indian patients with severe haemophilia A. Our aim was to study the role of immune regulatory gene polymorphisms in the development of inhibitors. Fourteen immune regulatory gene polymorphisms (IL1β, IL4, IL10, TNFA and CTLA4) were analysed in 120 patients with severe haemophilia A, i.e. 50 inhibitor positive patients, and 70 inhibitor negative control patients, by PCR-RFLP, DNA sequencing and allele-specific PCRs. The IL10 promoter 'GCC' haplotypes overall (P: 0.002, OR: 3.452, 95% CI: 1.607-7.416), and 'GCC/ATA' (P: 0.011, OR: 3.492, 95% CI: 1.402-8.696) haplotype, associated with high and intermediate IL10 production, respectively, were significantly higher in inhibitor positive patients, whereas the 'non-GCC' haplotypes overall (P: 0.002,OR: 0.290, 95% CI 0.135-0.622) and 'ATA/ATA' haplotype (P: 0.025, OR: 0.278, 95% CI: 0.096-0.802), associated with low IL10 synthesis, were significantly higher among inhibitor negative patients. The TNFA rs1799724 C/T heterozygote prevalence was significantly higher in the inhibitor positive group (P: 0.021, OR: 3.190, 95% CI: 1.273-7.990), whereas the other polymorphisms showed no statistically significant association with the presence of inhibitors. Different immune regulatory gene polymorphisms play a significant role as possible risk factors for the development of inhibitors in severe haemophilia A patients. © 2012 Blackwell Publishing Ltd.

  15. RHD gene polymorphism among RhD-negative Han Chinese

    Institute of Scientific and Technical Information of China (English)

    徐群; 张建业; 王勤友; 张世训; 司桂玲

    2003-01-01

    Objective To evaluate the status of eight RHD specific exons in 131 Han Chinese blood donors who were classified as RhD-negative by serological methods and explore the genomic structure of RHD gene among the Han Chinese. The Rh blood group system has the highest prevalence of polymorphisms among human blood group systems and is clinically significant in transfusion medicine. The Rh antigens are expressed on polypeptides encoded by two highly homologous genes, RHD and RHCE. Recent molecular studies have shown that the RhD-negative trait could be generated by multiple genetic mechanisms and is ethnic group-dependent.Methods The polymerase chain reaction using-sequence specific primers (PCR-SSP) was used to amplify exons 2, 3, 4, 5, 6, 7, 9 and 10 of RHD gene and exons 1, 2 and 5 of RHCE gene, as well as intron 4 in each of them.Results The 131 cases of RhD-negative phenotypes consisted of 60 ccee, 58 Ccee, 5 ccEe, 5 CcEe and 3 CCee. Among them, 83 with the Rh ccee or ccEe phenotypes (63.4%) lacked the eight RHD exons indicated above, while 26 cases with the Rh Ccee, CCee, CcEe phenotypes (19.9%) had all the RHD exons examined. Twenty-two individuals with the Ccee, CCee, CcEe phenotypes (16.8%) carried at least one RHD exon. The phenotypes of the RhD negative individuals carrying the RHD gene were Rh CC or Cc, but not cc. Conclusions Three classes of RhD-negative polymorphisms among a population of Han Chinese were observed. Antigen association analysis suggested the existence of a novel class of RhD-negative associated haplotype in Han Chinese. This haplotype consisted of a normal RHCE allele and a nonfunctional RHD gene. It may be beneficial to redefine the RhD-negative blood group among Chinese populations upon clarification of the mechanisms of RHD gene expression and RhD antigen immunization.

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

    Science.gov (United States)

    Armeni, Anastasia K; Assimakopoulos, Konstantinos; Marioli, Dimitra; Koika, Vassiliki; Michaelidou, Euthychia; Mourtzi, Niki; Iconomou, Gregoris; Georgopoulos, Neoklis A

    2017-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Interaction of DNA repair gene polymorphisms and aflatoxin B1 in the risk of hepatocellular carcinoma

    OpenAIRE

    2014-01-01

    Aflatoxin B1 (AFB1) is an important environmental carcinogen and can induce DNA damage and involve in the carcinogenesis of hepatocellular carcinoma (HCC). The deficiency of DNA repair capacity related to the polymorphisms of DNA repair genes might play a central role in the process of HCC tumorigenesis. However, the interaction of DNA repair gene polymorphisms and AFB1 in the risk of hepatocellular carcinoma has not been elucidated. In this study, we investigated whether six polymorphisms (i...

  19. Effect of IL-10 gene transfer on expression of IL-12,IL-15,IL-18 and IL-4 in mice heart transplantation rejection%白细胞介素10基因转染对小鼠心脏移植排斥反应中细胞因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    高思海; 潘铁成; 杨辰垣

    2004-01-01

    目的:探讨白细胞介素10(IL-10)基因转染对小鼠心脏移植排斥反应中IL-12、IL-15、IL-18和IL-4表达的影响.方法:采用小鼠颈部心脏移植模型,随机分为3组:对照组、移植组和IL-10组.于术后第5天取移植心脏,用逆转录聚合酶链式反应(RT-PCR)法观察IL-12、IL-15、IL-18、IL-4及IL-10的表达情况.结果:移植组IL-12、IL-15、IL-18表达与对照组比较明显升高,IL-10、 IL-4表达显著降低(均P<0.01).IL-10组IL-12、IL-15、IL-18表达与移植组比较明显降低,而IL-4及IL-10表达显著升高(均P<0.01).结论:IL-10基因转染抑制心脏移植排斥反应主要与其抑制IL-12、IL-15、IL-18等Th1型细胞因子的表达,促进Th2型细胞因子IL-4的表达,使免疫反应由Th1型向Th2型偏移有关.

  20. Association between Polymorphisms in Antioxidant Genes and Inflammatory Bowel Disease

    Science.gov (United States)

    Coelho, Rosa; Grácio, Daniela; Silva, Marco; Peixoto, Armando; Lago, Paula; Pereira, Márcia; Catarino, Telmo; Pinho, Salomé; Teixeira, João Paulo; Macedo, Guilherme; Annese, Vito

    2017-01-01

    Inflammation is the driving force in inflammatory bowel disease (IBD) and its link to oxidative stress and carcinogenesis has long been accepted. The antioxidant system of the intestinal mucosa in IBD is compromised resulting in increased oxidative injury. This defective antioxidant system may be the result of genetic variants in antioxidant genes, which can represent susceptibility factors for IBD, namely Crohn’s disease (CD) and ulcerative colitis (UC). Single nucleotide polymorphisms (SNPs) in the antioxidant genes SOD2 (rs4880) and GPX1 (rs1050450) were genotyped in a Portuguese population comprising 436 Crohn’s disease and 367 ulcerative colitis patients, and 434 healthy controls. We found that the AA genotype in GPX1 is associated with ulcerative colitis (OR = 1.93, adjusted P-value = 0.037). Moreover, we found nominal significant associations between SOD2 and Crohn’s disease susceptibility and disease subphenotypes but these did not withstand the correction for multiple testing. These findings indicate a possible link between disease phenotypes and antioxidant genes. These results suggest a potential role for antioxidant genes in IBD pathogenesis and should be considered in future association studies. PMID:28052094

  1. Association between angiotensin-converting-enzyme gene polymorphism and failure of renoprotective therapy

    NARCIS (Netherlands)

    vanEssen, GG; Rensma, PL; deZeeuw, D; Sluiter, WJ; Scheffer, H; Apperloo, AJ; deJong, PE

    1996-01-01

    Background Polymorphism in the gene for angiotensin-converting enzyme (ACE), especially the DD genotype, is associated with risk for cardiovascular disease. Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE gene polymorphism in patients with kidney disease who were in a tr

  2. Interleukin 10 gene promoter polymorphism and risk of diffuse large B cell lymphoma (DLBCL

    Directory of Open Access Journals (Sweden)

    Roba M. Talaat

    2014-01-01

    Conclusions: Taken together, our findings demonstrated that IL-10 promoter gene polymorphism (−1082 and −819 may not have an influence on the clinical outcome of DLBCL, especially in terms of overall secretion level. Further investigations of other cytokine gene polymorphisms will lead to a better understanding of the disease’s biological background.

  3. Association of angiotensin-converting enzyme, CYP46A1 genes polymorphism with senile cataract

    Directory of Open Access Journals (Sweden)

    Syed Tasleem Raza

    2017-01-01

    Conclusion: Findings of this study suggest that ACE and CYP46A1 genes polymorphism may be a predictive marker for early identification of population at risk of senile cataract. This potential role of ACE and CYP46A1 genes polymorphism as a marker of susceptibility to senile cataract needs further validation in studies involving larger number of patients from different regions.

  4. Association between angiotensin-converting-enzyme gene polymorphism and failure of renoprotective therapy

    NARCIS (Netherlands)

    vanEssen, GG; Rensma, PL; deZeeuw, D; Sluiter, WJ; Scheffer, H; Apperloo, AJ; deJong, PE

    1996-01-01

    Background Polymorphism in the gene for angiotensin-converting enzyme (ACE), especially the DD genotype, is associated with risk for cardiovascular disease. Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE gene polymorphism in patients with kidney disease who were in a

  5. Delayed allograft rejection in mice transgenic for a soluble form of the IL-4 receptor.

    Science.gov (United States)

    Maliszewski, C R; Morrissey, P J; Fanslow, W C; Sato, T A; Willis, C; Davison, B

    1992-09-01

    Accumulating evidence suggests that in serum and other biological fluids, cytokine binding is a property associated with soluble proteins, including a high-affinity soluble version of the IL-4 receptor (sIL-4R). While it is tempting to speculate that sIL-4R might act as a serum carrier protein or serve to inhibit or modulate IL-4 action, specific biological roles for sIL-4R remain to be established. To further assess the immunoregulatory and therapeutic potential of sIL-4R and other soluble receptors, we have created transgenic mice which constitutively express elevated levels of biologically active sIL-4R. Phenotypic characterization of lymphoid organs in sIL-4R transgenic mice revealed normal numbers of B and T cells and normal surface marker expression. Splenic lymphocytes displayed normal in vitro activities as measured by the PFC response and generation of cytotoxic T cells. In addition, antigen-specific IgE and IgG1 in vivo responses were similar in control and transgenic mice. Despite the apparent developmental normality of the sIL-4R transgenic mice, these animals were markedly deficient in the ability to reject cardiac allografts, suggesting that IL-4 is critical for the generation of alloreactivity. The results further suggest that the ability of sIL-4R to regulate IL-4 activities may be under the control of complex interactions that remain to be elucidated.

  6. Monocyte cell surface glycosaminoglycans positively modulate IL-4-induced differentiation toward dendritic cells.

    NARCIS (Netherlands)

    Dekker, E. den; Grefte, S.; Huijs, T.; Dam, G.B. ten; Versteeg, E.M.M.; Berk, L.C.J. van den; Bladergroen, B.A.; Kuppevelt, A.H.M.S.M. van; Figdor, C.G.; Torensma, R.

    2008-01-01

    IL-4 induces the differentiation of monocytes toward dendritic cells (DCs). The activity of many cytokines is modulated by glycosaminoglycans (GAGs). In this study, we explored the effect of GAGs on the IL-4-induced differentiation of monocytes toward DCs. IL-4 dose-dependently up-regulated the expr

  7. 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.

  8. 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.

  9. Association of interleukin-6 gene polymorphism with angina pectoris.

    Science.gov (United States)

    Amorim, Fernanda Gobbi; Campagnaro, Bianca Prandi; Tonini, Clarissa Loureiro; Norbim, Ana Paula Capua; Louro, Iuri Drummond; Vasquez, Elisardo Corral; Arruda, Jose Airton; Meyrelles, Silvana Santos

    2011-10-01

    In this study, we investigated the role of the -174G>C polymorphism of interleukin-6 (IL-6) as a predisposing factor to angina pectoris. Patients were separated into 2 groups: angina (N = 72) and nonangina (N = 71). There were no statistical differences between groups for all cardiovascular risk factors evaluated. The GG genotype frequency was 18% lower in the angina than in the non-angina group, whereas GC + CC was 18% higher in the angina group (P = .036). The frequency of G allele was 11% lower in the angina than in the nonangina group and C allele was 11% higher in the angina group (P = .043). Patients carrying the C allele showed a 2-fold increased risk for angina pectoris (P = .036). Our study demonstrates a high incidence of the -174G>C polymorphism of the IL-6 gene in patients with angina pectoris compared with those carrying the G allele, reinforcing the contribution of genetic factors to the symptoms of angina pectoris.

  10. Interleukin-10 Gene Polymorphisms are Associated With Freedom From Treatment Failure for Patients With Hodgkin Lymphoma

    Science.gov (United States)

    Schoof, Nils; Franklin, Jeremy; Fürst, Robert; Zander, Thomas; von Bonin, Frederike; Peyrade, Frederic; Trümper, Lorenz; Diehl, Volker; Engert, Andreas

    2013-01-01

    Background. Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by the production of various cytokines possibly involved in immune deregulation. Interleukin-10 (IL-10) serum levels have been associated with clinical outcome in patients with HL. Because host genetic variations are known to alter the expression and function of cytokines and their receptors, we investigated whether genetic variations influence clinical outcome of patients with HL. Methods. A total of 301 patients with HL who were treated within randomized trials by the German Hodgkin Study Group were included in this exploratory retrospective study. Gene variations of IL-10 (IL-10-597AC, rs1800872; IL-10-824CT, rs1800871; IL-10-1087AG, rs1800896; IL-10-3538AT, rs1800890; IL-10-6208CG, rs10494879; IL-10-6752AT, rs6676671; IL-10-7400InDel), IL-13 (IL-13-1069CT, rs1800925; IL-13Q144R, rs20541), and IL-4R (IL-4RI75V, rs1805010; IL-4RQ576R, rs1801275) were genotyped. Results. Inferior freedom from treatment failure (FFTF) was found in patients harboring the IL-10-597AA, IL-10-824TT, or the IL-10-1087AA genotype. In contrast, the IL-10-1087G-824C-597C haplotype present in about 48% of analyzed HL patients is nominally significant for a better FFTF in a Cox-Regression model accounting for stage and treatment. No associations were observed between the other IL-10 gene variations, IL-13-1069CT, IL-13Q144R, IL-4RI75V, IL-4RQ576R and the clinical outcome of patients with HL. Conclusions. Our study provides further evidence that proximal IL-10 promoter gene variations are associated with clinical course of patients with HL. However, treatment success and survival rates are already at a very high rate, supporting the need to design studies focusing on identification of predictors to reduce the side effects of therapy. PMID:23299779

  11. Haplotypes of NOS3 Gene Polymorphisms in Dilated Cardiomyopathy

    Science.gov (United States)

    Matsa, Lova Satyanarayana; Rangaraju, Advithi; Vengaldas, Viswamitra; Latifi, Mona; Jahromi, Hossein Mehraban; Ananthapur, Venkateshwari; Nallari, Pratibha

    2013-01-01

    Dilated Cardiomyopathy (DCM) is characterized by systolic dysfunction, followed by heart failure necessitating cardiac transplantation. The genetic basis is well established by the identification of mutations in sarcomere and cytoskeleton gene/s. Modifier genes and environmental factors are also considered to play a significant role in the variable expression of the disease, hence various mechanisms are implicated and one such mechanism is oxidative stress. Nitric Oxide (NO), a primary physiological transmitter derived from endothelium seems to play a composite role with diverse anti-atherogenic effects as vasodilator. Three functional polymorphisms of endothelial nitric oxide synthase (NOS3) gene viz., T-786C of the 5′ flanking region, 27bp VNTR in intron4 and G894T of exon 7 were genotyped to identify their role in DCM. A total of 115 DCM samples and 454 controls were included. Genotyping was carried out by PCR -RFLP method. Allelic and genotypic frequencies were computed in both control & patient groups and appropriate statistical tests were employed. A significant association of TC genotype (T-786C) with an odds ratio of 1.74, (95% CI 1.14 - 2.67, p = 0.01) was observed in DCM. Likewise the GT genotypic frequency of G894T polymorphism was found to be statistically significant (OR 2.10, 95% CI 1.34–3.27, p = 0.0011), with the recessive allele T being significantly associated with DCM (OR 1.64, 95% CI 1.18 - 2.30, p = 0.003). The haplotype carrying the recessive alleles of G894T and T-786C, C4bT was found to exhibit 7 folds increased risk for DCM compared to the controls. Hence C4bT haplotype could be the risk haplotype for DCM. Our findings suggest the possible implication of NOS3 gene in the disease phenotype, wherein NOS3 may be synergistically functioning in DCM associated heart failure via the excessive production of NO in cardiomyocytes resulting in decreased myocardial contractility and systolic dysfunction, a common feature of DCM

  12. Haplotypes of NOS3 gene polymorphisms in dilated cardiomyopathy.

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    Lova Satyanarayana Matsa

    Full Text Available Dilated Cardiomyopathy (DCM is characterized by systolic dysfunction, followed by heart failure necessitating cardiac transplantation. The genetic basis is well established by the identification of mutations in sarcomere and cytoskeleton gene/s. Modifier genes and environmental factors are also considered to play a significant role in the variable expression of the disease, hence various mechanisms are implicated and one such mechanism is oxidative stress. Nitric Oxide (NO, a primary physiological transmitter derived from endothelium seems to play a composite role with diverse anti-atherogenic effects as vasodilator. Three functional polymorphisms of endothelial nitric oxide synthase (NOS3 gene viz., T-786C of the 5' flanking region, 27bp VNTR in intron4 and G894T of exon 7 were genotyped to identify their role in DCM. A total of 115 DCM samples and 454 controls were included. Genotyping was carried out by PCR -RFLP method. Allelic and genotypic frequencies were computed in both control & patient groups and appropriate statistical tests were employed. A significant association of TC genotype (T-786C with an odds ratio of 1.74, (95% CI 1.14 - 2.67, p = 0.01 was observed in DCM. Likewise the GT genotypic frequency of G894T polymorphism was found to be statistically significant (OR 2.10, 95% CI 1.34-3.27, p = 0.0011, with the recessive allele T being significantly associated with DCM (OR 1.64, 95% CI 1.18 - 2.30, p = 0.003. The haplotype carrying the recessive alleles of G894T and T-786C, C4bT was found to exhibit 7 folds increased risk for DCM compared to the controls. Hence C4bT haplotype could be the risk haplotype for DCM. Our findings suggest the possible implication of NOS3 gene in the disease phenotype, wherein NOS3 may be synergistically functioning in DCM associated heart failure via the excessive production of NO in cardiomyocytes resulting in decreased myocardial contractility and systolic dysfunction, a common feature of DCM

  13. Relationship between polymorphisms of the genes associated with disease resistances and immune traits in the Northeast Hebao Pigs%东北民猪荷包猪抗性基因多态性及其与免疫指标的相关性研究

    Institute of Scientific and Technical Information of China (English)

    朱弘焱; 赵颂; 巴彩凤; 苏玉虹

    2011-01-01

    In order to analyze the polymorphism of FUT 1 and Mxl genes of Hebao Pigs, and the correlativity between polymorphism and immune traits, the PCR-RFLP was used to analyse the polymorphism of genes and the double-antibody sandwich enzyme-linked immunoassay (ELISA) was used to analyse the level of interferon-a (IFN-a) , interleukin-4 (IL-4) and secretory immunoglobulin A (slgA). Results indicated that Hebao Pigs had polymorphism with Hin6l of FUT 1 and Mxl genes and the advantages of genotypes were GG and AA, other sites didn't have polymorphism; and the levels of IFN-α, IL-4 and SlgA in Hebao pigs were higher those in Large White pigs. Our results suggested that the relativity between polymorphisms of genes associated with disease resistance and immune traits was not noticeable.%研究目的是检测荷包猪FUT 1和Mx1基因位点多态性及其与免疫指标的相关关系.采用PCR-RFLP技术分析基因多态性,采用ELISA方法检测免疫指标白介素-4(IL4)、分泌型免疫球蛋白A (sIgA)、α-干扰素(IFN-α)的表达量.结果表明,荷包猪FUT 1基因和Mx1基因Hin6I点酶切位点上显示多态性,优势基因型分别为GG和AA型,在Mx1基因其他两位点处未发现多态性;荷包猪免疫指标IL-4、sIgA、IFN-α的表达量明显高于大白猪(P<0.05),但抗性基因型与免疫指标间的相关性表现不明显.

  14. IL6 gene promoter polymorphisms and type 2 diabetes

    DEFF Research Database (Denmark)

    Huth, Cornelia; Heid, Iris M; Vollmert, Caren;

    2006-01-01

    Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C (rs1800796), have been investigated for association with type...... 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different...... countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found...

  15. A variety of gene polymorphisms associated with idiopathic granulomatous mastitis

    Science.gov (United States)

    Destek, Sebahattin; Gul, Vahit Onur; Ahioglu, Serkan

    2016-01-01

    Idiopathic granulomatous mastitis (IGM) is a rare and chronic inflammatory disorder. IGM mimics breast cancer regarding its clinical and radiological features. Etiology of IGM remains unclarified. Our patient was 37-year-old and 14 weeks pregnant. There was pain, redness and swelling in the right breast. The mass suggestive of malignancy was detected in sonography. Serum CA 125 and CA 15-3 levels were high. Genetic analysis was performed for the etiology. methylenetetrahydrofolate reductase (MTHFR) C 677 TT, β-fibrinogen-455 G>A, plasminogen activator inhibitor (PAI)-1 5 G/5 G, angiotensin-converting enzyme (ACE) I/D mutation was found. IGM was diagnosed by cor biopsy. An association was also reported between breast cancer and mutations in MTHFR-C 677 T, PAI-1, ACE genes. Genetic polymorphisms may involve in the development of IGM as it was seen in our case. Further studies should be conducted to better clarify this plausible association. PMID:27619324

  16. Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients.

    Directory of Open Access Journals (Sweden)

    Ambreen Ansari

    Full Text Available BACKGROUND: Pakistan ranks 7(th globally in terms of tuberculosis (TB disease burden (incidence 181/100000 pop./yr; prevalence of 329/pop./yr. Reports from different populations show variable associations of TB susceptibility and severity with cytokine gene polymorphisms. Tuberculosis clinical severity is multi-factorial and cytokines play a pivotal role in the modulation of disease severity. We have recently reported that the ratio of two key cytokines (IFNgamma and IL10 show significant correlation with the severity spectrum of tuberculosis. The objective of the current study was to analyze the frequency of cytokine gene polymorphisms linked to high and low responder phenotypes (IFNgamma +874 T(hi-->A(lo and IL10 -1082 G(lo-->A(hi in tuberculosis patients. METHODS AND FINDINGS: STUDY GROUPS WERE STRATIFIED ACCORDING TO DISEASE SITE AS WELL AS DISEASE SEVERITY: Pulmonary N = 111 (Minimal, PMN = 19; Moderate, PMD = 63; Advance, PAD = 29; Extra-pulmonary N = 67 (Disseminated DTB = 20, Localized LTB = 47 and compared with healthy controls (TBNA = 188. Genotype analyses were carried out using amplification refractory mutation system-PCR (ARMS-PCR and stimulated whole blood (WB culture assay was used for assessing cytokine profiles. Our results suggest that the IFNgamma +874 TT genotype and T allele was overrepresented in PMN (p = 0.01 and PMD (p = 0.02. IFNgamma +874 TT in combination with IL10 GG(lo genotypes showed the highest association (chi(2 = 6.66, OR = 6.06, 95% CI = 1.31-28.07, p = 0.01. IFNgamma AA(lo on the other hand in combination with IL10 GG(lo increased the risk of PAD (OR = 5.26; p = 0.005 and DTB (OR = 3.59; p = 0.045. CONCLUSION: These findings are consistent with the role of IL10 in reducing collateral tissue damage and the protective role of IFNgamma in limiting disease in the lung.

  17. Polymorphisms in MGP gene and their association with lead toxicity.

    Science.gov (United States)

    Shaik, Abjal Pasha; Jamil, Kaiser

    2009-03-01

    Matrix gamma-carboxy glutamic acid protein (MGP) is a 10-kDa secreted protein containing five residues of the vitamin K-dependent calcium binding amino acid gamma-carboxyglutamic acid (Gla). This study was carried out to examine the effects of MGP gene promoter polymorphism (T-138C) on blood lead levels (BLL) and hematological parameters in 113 battery manufacturing unit workers occupationally exposed to lead and 102 controls. Genotypes for the MGP T-138C polymorphism were determined by PCR and restriction fragment length digestion. BLL were determined by Anode Stripping Voltammetry using ESA Model 3010B Lead analyzer. Complete blood picture (CBP) was analyzed using ADVIA Cell counter for each sample. The frequencies of MGP-TT, CT and CC genotypes in our population were 38.6%, 44.3%, and 17.2%, respectively. The frequencies for T and C alleles were 0.612 and 0.386, respectively. Although BLL did not differ significantly among genotypes; they were higher in workers with TT/CT genotype compared to CC genotype subjects (76-88 microg/dL vs 22-45 microg/dL, p > 0.05). About 29.2% of volunteers (n = 33) from the occupationally exposed group had hemoglobin levels below 10.0 gms/dl. There was no significant difference in total white cell count and platelet count between occupational and non-exposed groups. The possible role of SNPs in the promoter region of MGP gene with relation to lead toxicity was investigated for the first time in the Indian population; although significance could not be achieved in this study, further assessments over a larger population size may help in better understanding of the consequences of lead exposure.

  18. Investigation of cytokine gene polymorphisms in patients with psoriasis vulgaris

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    Çiğdem Kekik Çınar

    2016-03-01

    Full Text Available Psoriasis is associated with cutaneous and systemic overexpression of several proinflammatory cytokines. The aim of this study was to investigate the relationship between susceptibility to psoriasis and polymorphisms of tumor necrosis factor alpha (TNF-α, interferon gamma (INF-γ, interleukin (IL-10, IL-6 and transforming growth factor beta (TGF-β. Eighty-nine patients with psoriasis and 201 healthy controls were enrolled into the study. The patient group was divided into 2 subgroups as early-onset (group 1 and late-onset (group 2. The cytokine gene polymorphisms in each group were determined by polymerase chain reaction-single specific primer. When the whole and only group 1 patients were compared with the controls, TGF-β TT/GC genotype was significantly high in the whole and group 1 patients. When we compared the group 1 and group 2, the frequency of IFN-γ AA genotype was found to be significantly high in group 1 which lost significance after Bonferroni correction. Patients with moderate symptoms had a significantly high frequency of IL-10 GCC/GCC genotype that did not remain significant after correction. These data from our small group of patients demonstrated that the only significant difference between the whole patient group and the controls was for TGF-β TT/GC genotype with a higher frequency in the patients. Due to the involvement of many other genes relating to the activity of Th1 cytokines, further studies are required to determine the molecular basis of the susceptibility to psoriasis.

  19. RENIN ANGIOTENSIN SYSTEM GENE POLYMORPHISMS IN CHILDREN WITH NEPHROTIC SYNDROM

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    Zh.P. Sharnova

    2006-01-01

    Full Text Available To investigate the role of the reninangiotensin system genes polymorphisms in develop and progression of nephrotic syndrom (NS in children we determined the genotypes of angiotensin converting enzyme (ACE, angiotensinogen (AGT and angiotensin ii receptor (ATII-R of 1 type in 80 russian children with ns including and 15 children with chronic renal failure (CRF. Genotype frequencies did not differ between patients with ns and controls (n = 165. The distribution of ace, AGT and ATII-R 1 type genotypes was similar among ns sub groups, such as focal segmental glomerulosclerosis (FSGS (n = 18, steroid-sensitive nephrotic syndrome (n = 32, nephrotic syndrome with hypertension and hemoturia (n = 22 and with control group. When ns subjects with CRF (n = 15 were compared with control, the prevalence of ace DD genotype was significantly higher (47% VS 21%; χ2 = 4,44; p < 0,05. Our results indicate that the DD genotype ace may be a factor of risk for the dеvеlopment of progressive renal impairment in the children with nephrotic syndrome. The analysis of treatment's effect with inhibitor of ace in groups patients with steroid resistant NS (SRNS demonstrated decreasing of renoprotective effect of this drugs in patients with id and dd genotypes com? Pared with ii genotype: the degree of blood pressure, proteinuria and the rate of glomerular filtration decrease was significantly lower (55,46 ± 9,25 VS 92,74 ± 25; р < 0,05 in these patients.Key words: nephrotic syndrom, chronic renal failure, polymorphism of genes, renin-angiotensin system.

  20. The association between osteopontin gene polymorphisms, osteopontin expression and sarcoidosis.

    Science.gov (United States)

    Lavi, Hadas; Assayag, Miri; Schwartz, Assaf; Arish, Nissim; Fridlender, Zvi G; Berkman, Neville

    2017-01-01

    Sarcoidosis is a systemic inflammatory disease of unknown etiology. Osteopontin (SPP1, OPN) is an extra cellular matrix glycoprotein and cytokine with a known role in granuloma formation and in autoimmune and inflammatory diseases. To determine whether plasma OPN levels are elevated in patients with sarcoidosis and compare the frequency of four single nucleotide polymorphism (SNPs) variants in the OPN gene in sarcoidosis patients compared to healthy controls. Demographic and clinical information, radiological studies and pulmonary function tests were evaluated in 113 patients with sarcoidosis and in 79 healthy controls. Blood samples were analyzed for SNPs of the OPN gene and for plasma OPN and CRP levels. Association between clinical features of disease and OPN levels as well as SNP frequencies was determined. Plasma OPN levels were higher in sarcoidosis patients than in healthy subjects, (median: 217 vs 122ng/ml, psarcoidosis patients and controls in the frequency of any of the SNPs evaluated. Presence of lung parenchymal involvement was associated with SNP distribution at rs1126772 (p = 0.02). We found no correlation between SNPs distribution and plasma OPN levels. Osteopontin protein levels are elevated in sarcoidosis. We found no evidence for an association between SNPs on the osteopontin gene and plasma OPN levels or the presence of sarcoidosis, however, an association between genotype and several phenotypic clinical parameters of disease was observed.

  1. Single nucleotide polymorphisms of myostatin gene in Chinese domestic horses.

    Science.gov (United States)

    Li, Ran; Liu, Dong-Hua; Cao, Chun-Na; Wang, Shao-Qiang; Dang, Rui-Hua; Lan, Xian-Yong; Chen, Hong; Zhang, Tao; Liu, Wu-Jun; Lei, Chu-Zhao

    2014-03-15

    The myostatin gene (MSTN) is a genetic determinant of skeletal muscle growth. Single nucleotide polymorphisms (SNP) in MSTN are of importance due to their strong associations with horse racing performances. In this study, we screened the SNPs in MSTN gene in 514 horses from 15 Chinese horse breeds. Six SNPs (g.26T>C, g.156T>C, g.587A>G, g.598C>T, g.1485C>T, g.2115A>G) in MSTN gene were detected by sequencing and genotyped using PCR-RFLP method. The g.587A>G and g.598C>T residing in the 5'UTR region were novel SNPs identified by this study. The g.2115A>G which have previously been associated with racing performances were present in Chinese horse breeds, providing valuable genetic information for evaluating the potential racing performances in Chinese domestic breeds. The six SNPs together defined thirteen haplotypes, demonstrating abundant haplotype diversities in Chinese horses. Most of the haplotypes were shared among different breeds with no haplotype restricted to a specific region or a single horse breed. AMOVA analysis indicated that most of the genetic variance was attributable to differences among individuals without any significant contribution by the four geographical groups. This study will provide fundamental and instrumental genetic information for evaluating the potential racing performances of Chinese horse breeds. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Incomplete deletion of IL-4Rα by LysM(Cre reveals distinct subsets of M2 macrophages controlling inflammation and fibrosis in chronic schistosomiasis.

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    Kevin M Vannella

    2014-09-01

    Full Text Available Mice expressing a Cre recombinase from the lysozyme M-encoding locus (Lyz2 have been widely used to dissect gene function in macrophages and neutrophils. Here, we show that while naïve resident tissue macrophages from IL-4Rαf(lox/deltaLysM(Cre mice almost completely lose IL-4Rα function, a large fraction of macrophages elicited by sterile inflammatory stimuli, Schistosoma mansoni eggs, or S. mansoni infection, fail to excise Il4rα. These F4/80(hiCD11b(hi macrophages, in contrast to resident tissue macrophages, express lower levels of Lyz2 explaining why this population resists LysM(Cre-mediated deletion. We show that in response to IL-4 and IL-13, Lyz2(loIL-4Rα(+ macrophages differentiate into an arginase 1-expressing alternatively-activated macrophage (AAM population, which slows the development of lethal fibrosis in schistosomiasis. In contrast, we identified Lyz2(hiIL-4Rα(+ macrophages as the key subset of AAMs mediating the downmodulation of granulomatous inflammation in chronic schistosomiasis. Our observations reveal a limitation on using a LysMCre mouse model to study gene function in inflammatory settings, but we utilize this limitation as a means to demonstrate that distinct populations of alternatively activated macrophages control inflammation and fibrosis in chronic schistosomiasis.

  3. Incomplete deletion of IL-4Rα by LysM(Cre) reveals distinct subsets of M2 macrophages controlling inflammation and fibrosis in chronic schistosomiasis.

    Science.gov (United States)

    Vannella, Kevin M; Barron, Luke; Borthwick, Lee A; Kindrachuk, Kristen N; Narasimhan, Prakash Babu; Hart, Kevin M; Thompson, Robert W; White, Sandra; Cheever, Allen W; Ramalingam, Thirumalai R; Wynn, Thomas A

    2014-09-01

    Mice expressing a Cre recombinase from the lysozyme M-encoding locus (Lyz2) have been widely used to dissect gene function in macrophages and neutrophils. Here, we show that while naïve resident tissue macrophages from IL-4Rαf(lox/delta)LysM(Cre) mice almost completely lose IL-4Rα function, a large fraction of macrophages elicited by sterile inflammatory stimuli, Schistosoma mansoni eggs, or S. mansoni infection, fail to excise Il4rα. These F4/80(hi)CD11b(hi) macrophages, in contrast to resident tissue macrophages, express lower levels of Lyz2 explaining why this population resists LysM(Cre)-mediated deletion. We show that in response to IL-4 and IL-13, Lyz2(lo)IL-4Rα(+) macrophages differentiate into an arginase 1-expressing alternatively-activated macrophage (AAM) population, which slows the development of lethal fibrosis in schistosomiasis. In contrast, we identified Lyz2(hi)IL-4Rα(+) macrophages as the key subset of AAMs mediating the downmodulation of granulomatous inflammation in chronic schistosomiasis. Our observations reveal a limitation on using a LysMCre mouse model to study gene function in inflammatory settings, but we utilize this limitation as a means to demonstrate that distinct populations of alternatively activated macrophages control inflammation and fibrosis in chronic schistosomiasis.

  4. Molecular genetics of Psoriasis (Principles, technology, gene location, genetic polymorphism and gene expression).

    Science.gov (United States)

    Al Robaee, Ahmad A

    2010-11-01

    Psoriasis is a common inflammatory skin disease with an etiology bases on both environmental and genetic factors. As is the case of many autoimmune diseases its real cause remains poorly defined. However, it is known that genetic factors contribute to disease susceptibility. The linkage analysis has been used to identify multiple loci and alleles that confer risk of the disease. Some other studies have focused upon single nucleotide polymorphisms (SNPs) for mapping of probable causal variants. Other studies, using genome-wide analytical techniques, tried to link the disease to copy number variants (CNVs) that are segments of DNA ranging in size from kilobases to megabases that vary in copy number. CNVs represent an important element of genomic polymorphism in humans and harboring dosage-sensitive genes may cause or predispose to a variety of human genetic diseases. The mechanisms giving rise to SNPs and CNVs can be considered as fundamental processes underlying gene duplications, deletions, insertions, inversions and complex combinations of rearrangements. The duplicated genes being the results of 'successful' copies are fixed and maintained in the population. Conversely, many 'unsuccessful' duplicates remain in the genome as pseudogenes. There is another form of genetic variations termed copy-neutral loss of heterozygosity (LOH) with less information about their potential impact on complex diseases. Additional studies would include associated gene expression variations with either SNPs or CNVs. Now many genetic techniques such as PCR, real time PCR, microarray and restriction fragment length analysis are available for detecting genetic polymorphisms, gene mapping and estimation of gene expression. Recently, the scientists have used these tools to define genetic signatures of disease, to understand genetic causes of disease and to characterize the effects of certain drugs on gene expression. This review highlights the principles, technology and applications on

  5. Endometriosis-associated infertility: GDF-9, AMH, and AMHR2 genes polymorphisms.

    Science.gov (United States)

    De Conto, Emily; Matte, Úrsula; Bilibio, João Paolo; Genro, Vanessa Krebs; Souza, Carlos Augusto; Leão, Delva Pereira; Cunha-Filho, João Sabino

    2017-08-22

    The purpose of this paper is to determine whether there is a correlation between polymorphisms in the growth differentiation factor-9 (GDF-9) gene and anti-Müllerian hormone (AMH) gene and its receptor, AMHR2, and endometriosis-associated infertility. This is a case-control study to evaluate whether there is a correlation between polymorphisms in the GDF-9 gene (SNPs determined by direct sequencing), AMH gene, AMHR2 (both SNPs determined by genotyping using TaqMan Allelic Discrimination), and endometriosis-associated infertility. The study included 74 infertile women with endometriosis and 70 fertile women (tubal ligation) as a control group. Patient age and the mean FSH levels were similar between the infertile with endometriosis and fertile without endometriosis groups. The frequency of genotypes between the groups for GDF-9 gene polymorphisms did not show statistical significance, nor did the AMHR2 gene polymorphism. However, the AMH gene polymorphism did show statistical significance, relating the polymorphic allele with infertility in endometriosis. We demonstrate that an SNP in the AMH gene is associated with infertility in endometriosis, whereas several SNPs in the GDF-9 gene and the - 482A G SNP in the AMHR2 gene were found to be unrelated.

  6. Neuroantibodies (NAB) in African-American Children with Heavy Metal Exposures are Associated with Cytokine and Human Leukocyte Antigen (HLA) Polymorphisms (SNP)

    Science.gov (United States)

    Polymorphisms in cytokine and HLA genes are associated with allergies, autoimmunity and neurodegeneration (ND). Samples from 131 African-American children (71 males; 60 females) in the Mechanistic Indicators of Childhood Asthma (MICA) study were used to determine SNPs of IL-4, IL...

  7. Association of Inflammatory Gene Polymorphisms and Conventional Risk Factors With Arterial Stiffness by Age

    OpenAIRE

    ,

    2013-01-01

    Background Inflammatory gene polymorphisms are potentially associated with atherosclerosis risk, but their age-related effects are unclear. To investigate the age-related effects of inflammatory gene polymorphisms on arterial stiffness, we conducted cross-sectional and 5-year follow-up studies using the cardio-ankle vascular index (CAVI) as a surrogate marker of arterial stiffness. Methods We recruited 1850 adults aged 34 to 69 years from the Japanese general population. Inflammatory gene pol...

  8. Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population

    OpenAIRE

    2014-01-01

    Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Oc...

  9. Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population

    OpenAIRE

    2013-01-01

    Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Oc...

  10. Cytokine Gene Polymorphisms support diagnostic monitoring of Romanian Multiple Myeloma patients

    OpenAIRE

    2011-01-01

    Introduction: cytokines and their receptor genes are very polymorphic. SNPs in the promotor region of the gene may influence the rate of cytokine secretion and may affect the biological activity of the encoded cytokine. A number of cytokines and cytokine receptors have been directly linked to the development of human cancers. The aim of our study was to determine the cytokine gene polymorphism in Romanian multiple myeloma patients. Material and methods: cytokine genotyping was performed in 80...

  11. Angiotensin converting enzyme gene polymorphism in type II diabetics with nephropathy

    OpenAIRE

    Naresh, V. V. S.; Reddy, A. L. K.; Sivaramakrishna, G.; Sharma, P. V. G. K.; Vardhan, R. V.; Kumar, V. Siva

    2009-01-01

    Nephropathy is an important and a frequent complication of long-term type II diabetic nephropathy. Strong evidence exists that genetic predisposition plays a major role in the development of diabetic nephropathy. Recent studies have implicated association between angiotensin converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and nephropathy. The deletion gene polymorphism of ACE gene has been shown to be associated with increased activity of this enzyme. This study examines th...

  12. Polymorphisms in mucin genes in the development of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Rong; Wen; Fang; Gao; Cheng-Jiang; Zhou; Yan-Bin; Jia

    2015-01-01

    Gastric cancer(GC) is the third leading cause of cancerrelated death worldwide.In areas of high prevalence,such as Japan,South Korea and China,most cases of GC are related to Helicobacter pylori(H.pylori),which involves well-characterized sequential stages,including infection,atrophic gastritis,intestinal metaplasia,dysplasia,and GC.Mucins are the most abundant highmolecular-weight glycoproteins in mucus,which is the first line of defense and plays a major role in blocking pathogenic factors.Normal gastric mucosa shows expression of MUC1,MUC5 AC and MUC6 that is specific to cell type.However,the specific pattern of MUC1,MUC5 AC and MUC6 expression is changed in gastric carcinogenesis,accompanied by de novo expression of secreted MUC2.Recent studies have provided evidence that variations in these mucin genes affect many steps of GC development,such as H.pylori infection,and gastric precancerous lesions.In this review,we focus on studies of the association between polymorphisms in mucin genes and development of GC.This information should be helpful for the early detection,surveillance,and treatment of GC.

  13. Effects of IL-10 and IL-4 on LPS-induced transcription factors (AP-1, NF-IL6 and NF-kappa B) which are involved in IL-6 regulation

    NARCIS (Netherlands)

    Dokter, Willem; Koopmans, S.B.; Vellenga, E

    1996-01-01

    Interleukin-10 (IL-10), like IL-4, is known to inhibit cytokine expression in activated human monocytes. We showed that both IL-10 and IL-4 inhibit LPS-induced IL-6 mRNA and protein expression by inhibiting the transcription rate of the IL-6 gene. The strong inhibition of the IL-6 transcription rate

  14. Mutation screening in the human epsilon-globin gene using single-strand conformation polymorphism analysis.

    Science.gov (United States)

    Papachatzopoulou, Adamantia; Menounos, Panagiotis G; Kolonelou, Christina; Patrinos, George P

    2006-02-01

    The human epsilon-globin gene is necessary for primitive human erythropoiesis in the yolk sac. Herein we report a non-radioactive single-strand conformation polymorphism (SSCP) approach to screen the human epsilon-globin gene and its regulatory regions for possible mutations and single-nucleotide polymorphisms in normal adult subjects, in order to determine those genomic regions, which are not necessary for its proper regulation and function. We identified no sequence variations apart from the expected 5'epsilon /HincII polymorphism in the fragments analyzed, suggesting that genomic alterations in the epsilon-globin gene are most likely incompatible with normal erythropoiesis and proper embryonic development.

  15. DNA polymorphism at locus-2 of growth hormone gene of Madura cattle

    Directory of Open Access Journals (Sweden)

    NITA ETIKAWATI

    2003-01-01

    Full Text Available The objectives of the research were to detect DNA polymorphism at locus 2 of bovine growth hormone gene of Madura cattle and to know its genetic diversity. DNA polymorphisms and their effect on phenotypic traits have been studied widely in dairy cattle but not for beef cattle, especially for Indonesian local cattle. Polymorphism was detected using PCR-RFLP using primer GH-5 and GH-6 for amplifying locus 2 of growth hormone gene. Genetic diversity was analyzed based on the formula of Nei (1973, 1975. DNA polymorphism was found on locus 2 of growth hormone gene using MspI restriction enzyme. This polymorphism may be caused the lost of restriction MspI site. The genetic diversity was 0.4422.

  16. The association between osteopontin gene polymorphisms, osteopontin expression and sarcoidosis

    Science.gov (United States)

    Lavi, Hadas; Assayag, Miri; Schwartz, Assaf; Arish, Nissim; Fridlender, Zvi G.; Berkman, Neville

    2017-01-01

    Background Sarcoidosis is a systemic inflammatory disease of unknown etiology. Osteopontin (SPP1, OPN) is an extra cellular matrix glycoprotein and cytokine with a known role in granuloma formation and in autoimmune and inflammatory diseases. Objective To determine whether plasma OPN levels are elevated in patients with sarcoidosis and compare the frequency of four single nucleotide polymorphism (SNPs) variants in the OPN gene in sarcoidosis patients compared to healthy controls. Methods Demographic and clinical information, radiological studies and pulmonary function tests were evaluated in 113 patients with sarcoidosis and in 79 healthy controls. Blood samples were analyzed for SNPs of the OPN gene and for plasma OPN and CRP levels. Association between clinical features of disease and OPN levels as well as SNP frequencies was determined. Results Plasma OPN levels were higher in sarcoidosis patients than in healthy subjects, (median: 217 vs 122ng/ml, p<0.001). Area under the curve for receiver operator curves (ROC) was 0.798 (0.686–0.909 95% CI.) No differences were observed between sarcoidosis patients and controls in the frequency of any of the SNPs evaluated. Presence of lung parenchymal involvement was associated with SNP distribution at rs1126772 (p = 0.02). We found no correlation between SNPs distribution and plasma OPN levels. Conclusions Osteopontin protein levels are elevated in sarcoidosis. We found no evidence for an association between SNPs on the osteopontin gene and plasma OPN levels or the presence of sarcoidosis, however, an association between genotype and several phenotypic clinical parameters of disease was observed. PMID:28253271

  17. Human leucocyte antigens and cytokine gene polymorphisms and tuberculosis

    Directory of Open Access Journals (Sweden)

    A Akgunes

    2011-01-01

    Full Text Available Purpose: Several genes encoding different cytokines and human leucocyte antigens (HLA may play crucial roles in host susceptibility to tuberculosis (TB. Our objective was to investigate whether these genes might be associated with protection from or susceptibility to TB. Materials and Methods: Genomic DNA from patients with TB (n = 30 and ethnically matched controls (n = 30 was genotyped by using sequence-specific primers-polymerase chain reaction and sequence-specific oligonucletid methods. Results: Our results demonstrated that HLA-CwFNx0101 [P = 0.05, odds ration (OR (95% confidence interval = 2.269 (1.702-3.027] allele frequency was significantly more common in TB patients than in healthy controls, and HLA-CwFNx0101 may be associated with susceptibility to TB. Analysis of cytokine allele frequencies showed that interleukin (IL-10, -819 C and -592 C alleles was significantly more common in TB patients than in controls (pc: 0.038 and 0.017, respectively. From the IL-10 cluster, a positive significant difference was found at positions -1082 and -592 C/C (pc: 0.027 and 0.054, respectively genotypes. Although these differences could be explained by the highest frequency of C/C and G/G homozygous patients with TB, in contrast to the control group, statistically significant differences for the C/C genotype however were lost after Bonferroni correction of the P-values. Conclusion: Altogether, our results suggest that the polymorphisms in HLA (class I and cytokine (IL-10 genes may affect the susceptibility to TB and increase the risk of developing the disease.

  18. Signal transduction through the IL-4 and insulin receptor families.

    Science.gov (United States)

    Wang, L M; Keegan, A; Frankel, M; Paul, W E; Pierce, J H

    1995-07-01

    Activation of tyrosine kinase-containing receptors and intracellular tyrosine kinases by ligand stimulation is known to be crucial for mediating initial and subsequent events involved in mitogenic signal transduction. Receptors for insulin and insulin-like growth factor 1 (IGF-1) contain cytoplasmic tyrosine kinase domains that undergo autophosphorylation upon ligand stimulation. Activation of these receptors also leads to pronounced and rapid tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in cells of connective tissue origin. A related substrate, designated 4PS, is similarly phosphorylated by insulin and IGF-1 stimulation in many hematopoietic cell types. IRS-1 and 4PS possess a number of tyrosine phosphorylation sites that are within motifs that bind specific SH2-containing molecules known to be involved in mitogenic signaling such as PI-3 kinase, SHPTP-2 (Syp) and Grb-2. Thus, they appear to act as docking substrates for a variety of signaling molecules. The majority of hematopoietic cytokines bind to receptors that do not possess intrinsic kinase activity, and these receptors have been collectively termed as members of the hematopoietin receptor superfamily. Despite their lack of tyrosine kinase domains, stimulation of these receptors has been demonstrated to activate intracellular kinases leading to tyrosine phosphorylation of multiple substrates. Recent evidence has demonstrated that activation of different members of the Janus family of tyrosine kinases is involved in mediating tyrosine phosphorylation events by specific cytokines. Stimulation of the interleukin 4 (IL-4) receptor, a member of the hematopoietin receptor superfamily, is thought to result in activation of Jak1, Jak3, and/or Fes tyrosine kinases.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Gene-gene, gene-environment, gene-nutrient interactionsand single nucleotide polymorphisms of inflammatorycytokines

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Inflammation plays a significant role in the etiologyof type 2 diabetes mellitus (T2DM). The rise in thepro-inflammatory cytokines is the essential step inglucotoxicity and lipotoxicity induced mitochondrialinjury, oxidative stress and beta cell apoptosis inT2DM. 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, tissueplasminogen activator, fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strongenvironmental influence; exhibiting a polygenic modeof inheritance. Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatorycytokines have been reported as a riskfor T2DM. Not all the SNPs have been confirmed byunifying results in different studies and wide variationshave been reported in various ethnic groups. Theinter-ethnic variations can be explained by the factthat gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions. Thisreview highlights the impact of these interactions ondetermining the role of single nucleotide polymorphismof IL-6, TNF-α, resistin and adiponectin in pathogenesisof T2DM.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Gene polymorphisms of intracerebral hemorrhage in Chinese population: a systematic review

    Institute of Scientific and Technical Information of China (English)

    谭贤佩

    2014-01-01

    Objective To assess the genes polymorphisms associated with intracerebral hemorrhage(ICH)in Chinese quantitatively or qualitatively by searching all case control studies related comprehensively.Methods Odds ratio(OR)and 95%confidence intervals(95%CI)were determined for each polymorphism using fixed or random model with Revman 5.1.Results Statistically significant associations with ICH were

  2. Polymorphisms in the NPY and AGRP genes and body fatness in Dutch adults.

    NARCIS (Netherlands)

    Rossum, Caroline T M van; Pijl, H; Adan, R A H; Hoebee, Barbara; Seidell, J C

    2006-01-01

    OBJECTIVE: To investigate the association between DNA polymorphisms in the NPY and AGRP genes and body fatness. DESIGN AND METHODS: The association between the AGRP Ala67Thr or the NPY Leu7Pro polymorphisms and indicators of body fatness (baseline leptin levels, body mass index (BMI) values and

  3. Polymorphisms in Dopamine System Genes Are Associated with Individual Differences in Attention in Infancy

    Science.gov (United States)

    Holmboe, Karla; Nemoda, Zsofia; Fearon, R. M. Pasco; Csibra, Gergely; Sasvari-Szekely, Maria; Johnson, Mark H.

    2010-01-01

    Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase ("COMT") and the…

  4. APOLIPOPROTEIN E GENE POLYMORPHISMS ARE NOT ASSOCIATED WITH DIABETIC RETINOPATHY: THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY

    Science.gov (United States)

    PURPOSE: Polymorphism of the apolipoprotein E (APOE) gene has been associated with dyslipidemia and cardiovascular disease. This study examines the association of APOE polymorphisms and diabetic retinopathy. DESIGN: Population-based cross-sectional study. METHODS: We studied 1,398 people aged 49 to ...

  5. Restriction fragment length polymorphism of two HLA-B-associated transcripts genes in five autoimmune diseases

    DEFF Research Database (Denmark)

    Fugger, L; Morling, N; Ryder, L P;

    1991-01-01

    The restriction fragment length polymorphism of the two human HLA-B-associated transcripts (BATs) genes, BAT1 and BAT2, identifying polymorphic bands of 12, 8, 2.5, and 1.1 kb, and at 3.3, 2.7, 2.3, and 0.9 kb, respectively, was investigated in patients with primary biliary cirrhosis (PBC), syste...

  6. Angiotensin-converting enzyme gene I/D polymorphism and renal disease

    NARCIS (Netherlands)

    Navis, G; van der Kleij, FGH; de Zeeuw, D; de Jong, PE

    1999-01-01

    In recent years a vast amount of data has been published on the association between the insertion/deletion (VD) polymorphism of the gene coding for angiotensin-converting enzyme and renal disease. It has be come clear that the polymorphism does not affect the prevalence of renal disease. However, da

  7. Polymorphisms in thrombophilic genes are associated with deep venous thromboembolism in an Iranian population

    Directory of Open Access Journals (Sweden)

    Malak Farajzadeh

    2014-12-01

    We concluded that the prevalence of FV (G1691A and A4070G and PAI-1 4G/5G polymorphisms increased the risk of DVT occurrence in subjects. These findings provide additional evidence to support the hypothesis that thrombophilic gene polymorphisms are involved in vascular thromboembolism.

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

    DEFF Research Database (Denmark)

    Ravn, Lasse S; Benn, Marianne; Nordestgaard, Børge G

    2008-01-01

    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...

  9. Serotonin transporter gene polymorphisms in irritable bowel syndrome and their impact on tegaserod treatment

    Institute of Scientific and Technical Information of China (English)

    李瑜元

    2006-01-01

    Objective To investigate the serotonin reuptake transporter (SERT) genetic polymorphisms in the 5 -hydroxytryptamine (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) and the variable number tandem repeats (VNTRs) in intron 2 among Chinese people, and their relationship to the pathogenesis of irritable bowel syndrome (IBS);and to investigate the im-

  10. Association between polymorphisms in IL21 gene and risk for sepsis.

    Science.gov (United States)

    Miao, Tianyu; Pu, Yan; Zhou, Bin; Chen, Peng; Wang, Yanyun; Song, Yaping; Zhao, Jichun; Zhang, Lin

    2017-02-01

    Sepsis is now the leading cause of death in the noncardiovascular intensive care unit (ICU). To investigate whether polymorphisms in IL21 gene contribute to sepsis susceptibility. Three single-nucleotide polymorphisms of IL21 (rs907715, rs2055979, rs12508721) were genotyped by TaqMan assay in patients with sepsis and control subjects. Polymorphisms rs2055979 and rs12508721 in IL21 were more frequent in sepsis patients compared to general population. But allele frequency of rs907715 was not significantly different between sepsis patients and control subjects. Polymorphisms in IL21 may be associated with sepsis risk.

  11. Lack of Arg972 polymorphism in the IRS1 gene in Parakanã Brazilian Indians.

    Science.gov (United States)

    Bezerra, Rosângela M N; Chadid, Thiago T; Altemani, Claúdia M; Sales, Teresa S I; Menezes, Raimundo; Soares, Manoel C P; Saad, Sara T O; Saad, Mario J A

    2004-02-01

    Several polymorphisms in the insulin receptor substrate-1 (IRS1) gene have been reported in the last years. The most common IRS1 variant, a Gly --> Arg substitution at codon 972 (Arg972 IRS1), is more prevalent among subjects who have features of insulin resistance syndrome associated, or not, with type 2 diabetes in European populations. To determine whether the absence of IRS1 polymorphism is a more general characteristic of Paleo-Indian-derived populations, we examined the Arg972 IRS1 polymorphism in Parakanã Indians and found a lack of this polymorphism in the Parakanã population.

  12. Butyrate enhances antibacterial effects while suppressing other features of alternative activation in IL-4-induced macrophages.

    Science.gov (United States)

    Fernando, Maria R; Saxena, Alpana; Reyes, José-Luis; McKay, Derek M

    2016-05-15

    The short-chain fatty acid butyrate is produced by fermentation of dietary fiber by the intestinal microbiota; butyrate is the primary energy source of colonocytes and has immunomodulatory effects. Having shown that macrophages differentiated with IL-4 [M(IL-4)s] can suppress colitis, we hypothesized that butyrate would reinforce an M(IL-4) phenotype. Here, we show that in the presence of butyrate M(IL-4)s display reduced expression of their hallmark markers Arg1 and Ym1 and significantly suppressed LPS-induced nitric oxide, IL-12p40, and IL-10 production. Butyrate treatment likely altered the M(IL-4) phenotype via inhibition of histone deacetylation. Functionally, M(IL-4)s treated with butyrate showed increased phagocytosis and killing of bacteria, compared with M(IL-4) and this was not accompanied by enhanced proinflammatory cytokine production. Culture of regulatory T cells with M(IL-4)s and M(IL-4 + butyrate)s revealed that both macrophage subsets suppressed expression of the regulatory T-cell marker Foxp3. However, Tregs cocultured with M(IL-4 + butyrate) produced less IL-17A than Tregs cocultured with M(IL-4). These data illustrate the importance of butyrate, a microbial-derived metabolite, in the regulation of gut immunity: the demonstration that butyrate promotes phagocytosis in M(IL-4)s that can limit T-cell production of IL-17A reveals novel aspects of bacterial-host interaction in the regulation of intestinal homeostasis.

  13. Association of Vitamin D Receptor Gene Polymorphisms with Calcium Oxalate Calcul us Disease

    Institute of Scientific and Technical Information of China (English)

    王少刚; 刘继红; 胡少群; 叶章群

    2003-01-01

    To study the relationship between polymorphism of vitamin D receptor (VDR) allele with formation of calcium oxalate calculus and find the predisposing genes of calcium oxalate calculus, we screened out 150 patients who suffered from calcium oxalate calculus. 36 of them had idiopathic hypercalciuria according to analysis of calculus component and assay of urine calcium. The polymorphisms of VDR gene Taq1, Apa1 and Fok1 were detected using PCR-RFLP technique and the correlation were analyzed between the polymorphism and urinary calculus or between the polymorphism and hypercalciuria. The difference in each genotypic frequency of the allele of promoter Fok1 between calculus group and healthy group or between idiopathic hypercalciuria calculus group and health group was significant. The content of 24-h urine calcium of those who had genotype ff was obviously higher than that of those who have other genotypes in the same group. There was no significant difference in the polymorphism of gene Apa1 and Taq1 between each two groups. It is concluded that hypercalciuria and calcium oxalate calculus were related to the polymorphism of VDR gene's promoter Fok1 allele, but it had nothing to do with the polymorphism of gene Apa1 and Taq1. The genotype ff was a candidate heredity marker of calcium calculus disease.

  14. RELN gene polymorphisms and susceptibility to autism in Chinese Han population.

    Science.gov (United States)

    Tian, Peichao

    2012-01-01

    Single nucleotide polymorphisms (SNPs) in the Reelin gene (RELN) are likely candidates to confer risk for autism. The objective of the present study is to investigate the association of RELN gene SNPs with autism. A total of 367 Chinese Han subjects were recruited, including 186 autism patients and 181 unrelated healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods were used to detect RELN gene polymorphisms. The association between SNPs and autism was analyzed in this study. The g.333509A>C in intron12 and g.504742G>A in exon60 were detected in the RELN gene and a significant association was found between the g.504742G>A polymorphism and autism. Allele and genotype frequencies for the g.504742G>A polymorphism in autistic patients were significantly different for healthy subjects. There was no significantly difference in g.333509A>C polymorphism and autism in the studied populations. Our findings indicated that g.333509A>C was not significantly associated with autism. The g.504742G>A polymorphic variant in the RELN gene might affect subjects susceptibility toward autism in Chinese Han population.

  15. emm Gene Polymorphism among Streptococcus pyogenes Isolated from

    Directory of Open Access Journals (Sweden)

    Mollaii Hamid

    2009-10-01

    Full Text Available DNA sequencing is the most conclusive method for emm (M protein gene typing of Streptococcus pyogenes. This method is not a feasible approach in developing countries where streptococcal infection is widespread among adults and children. Alternatively the PCR-RFLP has the potential for rapid screening of different types of S. pyogenes. To document the emm type distribution of S. pyogenes in a group of patients suffering from pharyngitis, the restriction fragment length polymorphism (RFLP profile of 50 isolates were analyzed. By using Hae III+ HincII (double digestion and Dde I restriction enzymes and based on RFLP, the profile patterns of the isolates were compared. The analysis of data identified 15 distinct RFLP patterns for Hae III+ Hinc II and 13 patterns for Dde I. They differ from each other by at least one band. Although the number of isolates was not sufficient to make any epidemiological conclusion, but the finding demonstrated that the S. pyogenes population among pateints was heterogeneous. Regarding the PCR method, we managed to improve the results by modification of CDC protocol in three different ways. This study was conducted in normal circumstances when pharyngitis was at the peak seasonal incident. However emm amplicon restriction digest analysis is a valuable tool for rapid analysis of S. pyogenes infection in more important situation like outbreaks and in selected type of study like consideration of nosocomial infection.

  16. Associations between phenylthiocarbamide gene polymorphisms and cigarette smoking.

    Science.gov (United States)

    Cannon, Dale S; Baker, Timothy B; Piper, Megan E; Scholand, Mary Beth; Lawrence, Daniel L; Drayna, Dennis T; McMahon, William M; Villegas, G Martin; Caton, Trace C; Coon, Hilary; Leppert, Mark F

    2005-12-01

    Phenotypic evidence indicates that the ability to taste the bitter compounds phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) may protect against cigarette smoking. In this study, PTC gene haplotypes were found to be associated with both the odds of being a smoker and the importance of cigarette taste as a smoking motive. Smokers (n = 384) and nonsmokers (n = 183) were genotyped for polymorphisms that affect taste sensitivity to PTC and PROP. The "taster" PAV haplotype, relative to the "nontaster" AVI haplotype, was predicted to be associated with reduced odds of being a smoker and lower taste motivation as measured by the Wisconsin Inventory of Smoking Dependence Motives-68 taste/sensory processes scale. The results did not support the predicted association between the PAV and AVI haplotypes and smoker odds, but the AAV haplotype, which confers intermediate PTC/PROP taste sensitivity, was associated with reduced smoker prevalence (49% vs. 70%), chi(2)(1, N = 567) = 10.392, p = .001. The predicted relationship between PAV and AVI and taste motivation was found, F(2, 348) = 3.303, p = .038. The results encourage further exploration of the role of taste/sensory processes in tobacco dependence.

  17. Gene Polymorphisms and Chemotherapy in Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Kayo OSAWA

    2009-01-01

    The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism ofirrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite, SN-38, which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin, carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine, paclitaxel, docetaxel, or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1, XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinudeotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity

  18. Gene Polymorphisms and Chemotherapy in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Kayo OSAWA

    2009-08-01

    Full Text Available The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite, SN-38, which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin, carboplatin are being used in combination with new cytotoxic drugs such as gemcitabine, paclitaxel, docetaxel, or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1, XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR

  19. Association between Alzheimer's disease and the NOS3 gene Glu298Asp polymorphism.

    Science.gov (United States)

    Hua, Ye; Zhao, Hui; Kong, Yuenan; Lu, Xiaojie

    2014-04-01

    The Glu298Asp gene polymorphism in NOS3 gene has been extensively investigated for association to Alzheimer's disease (AD), however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of NOS3 Glu298Asp polymorphism and AD risk by using meta-analysis. All eligible case-control studies were searched in PubMed and Embase. Odds ratios (OR) with the 95% confidence intervals (CI) were used to assess the association. A total of 5522 cases and 4877 controls in 20 case-control studies were included. Obvious heterogeneity among studies was detected, and no significant association was observed between the NOS3 Glu298Asp polymorphism and AD risk. After exclusion of three studies, the heterogeneity disappeared and still no association was observed. In the subgroup analysis by ethnicity, we did not find any significant association between this polymorphism and AD risk in both Asians and Caucasians. This meta-analysis suggested that the NOS3 Glu298Asp gene polymorphism is not a strong risk factor for AD. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of NOS3 gene and AD risk, more studies with large groups of patients are required.

  20. Alu insertion/deletion of ACE gene polymorphism might not affect ...

    African Journals Online (AJOL)

    Widodo

    2016-09-03

    Sep 3, 2016 ... Received 2 May 2016; accepted 1 August 2016. Available ... The Egyptian Journal of Medical Human Genetics (2017) 18, 187–191. HOSTED BY ..... insertion–deletion polymorphism of ACE gene and Alzheimer's · disease in ...

  1. Vitamin D status, receptor gene BsmI (A/G) polymorphism and ...

    African Journals Online (AJOL)

    Rasha Rizk Elzehery

    2016-12-05

    Dec 5, 2016 ... diagnosed as breast cancer admitted at Mansoura Oncology Center,. Mansoura University ... BsmI VDR polymorphism is located within intron 8 of the gene. ... Distribution of VDR BsmI genotypes in both cancer patients and.

  2. Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes

    DEFF Research Database (Denmark)

    Venkatesan, Meera; Gadalla, Nahla B; Stepniewska, Kasia

    2014-01-01

    Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated...

  3. Role of TLR4 gene polymorphisms in the colorectal cancer risk ...

    African Journals Online (AJOL)

    Saniya Nissar

    2016-05-26

    May 26, 2016 ... Conclusion: Our results suggest that TLR4 gene polymorphism is not a key modulator of the risk ... regulators in maintaining the balance between commensal ..... mation, and energy-related factors: a novel pathway of cancer.

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

    Directory of Open Access Journals (Sweden)

    Marina L Butovskaya

    Full Text Available 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.

  5. EFFECTS OF VITAMIN D RECEPTOR GENE POLYMORPHISMS ON SUSCEPTIBILITY TO TYPE 1 DIABETES MELLITUS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes mellitus (T1DM) in the Chinese Han population.Method One hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamI.Results The frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects (P=0.033) while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms.Conclusion The BsmI polymorphism of VDR gene may be associated with the susceptibility to T1DM in the Chinese Hah population of Beijing.

  6. Association of Interleukin 27 gene polymorphism and risk of Hepatitis B viral infection in Egyptian population

    Directory of Open Access Journals (Sweden)

    Yasser B.M. Ali

    2014-01-01

    Conclusion: Our data suggested that polymorphisms in the IL-27 gene may not contribute to HBV susceptibility. Further studies with large sample size should be conducted to validate these results in Egyptian population.

  7. 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

  8. Sirtuin 1 gene rs2273773 C>T single nucleotide polymorphism and ...

    African Journals Online (AJOL)

    Aida Abdeen Mahmoud

    2015-12-24

    Dec 24, 2015 ... polymorphism and protein oxidation markers in asthmatic ... In this investigation, we aimed to study SIRT-1 gene rs2273773 C > T single nucleotide polymor- ..... proliferator-activated receptor-c (PPAR-c), PPAR-c coactiva-.

  9. Analysis of allelic expression patterns of IL-2, IL-3, IL-4, and IL-13 in human CD4+ T cell clones.

    NARCIS (Netherlands)

    Bayley, J.P.; Bakker, AM; Kaijzel, EL; Wierenga, EA; Pouw Kraan, van der C.T.M.; Huizinga, T.W.; Verweij, C.L.

    2003-01-01

    The occurrence of monoallelic expression of cytokine genes in single cells has been convincingly demonstrated, but there have been few reports of this phenomenon in T cell clones. Here we describe studies on the expression of alleles of the human genes encoding IL-2, IL-3, IL-4, and IL-13 in human C

  10. Association of mannan-binding lectin gene polymorphisms with progression of severe lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    常欣蓓

    2014-01-01

    Objective To investigate the association of single nucleotide polymorphisms(SNPs)of the mannan-binding lectin(MBL)gene with serum levels,development,progression and prognosis of severe lupus nephritis(LN).Methods A total of 107 severe lupus nephritis patients were enrolled in the study from January 2003 to October2013.Integrated capillary electrophoresis was used to detect MBL gene polymorphism in peripheral blood

  11. Correlation between PON1 gene polymorphisms and breast cancer risk: a Meta-analysis

    OpenAIRE

    Wen, Yayuan; Huang, Zemin; Zhang, Xiaohua; Gao, Bo; He, Yujun

    2015-01-01

    Objective: A number of studies have investigated the relationship between the PON1 gene polymorphisms and breast cancer risk, but the conclusions are not consistent. In this paper, a meta-analysis was conducted to explore the possible reasons for these inconsistencies, expecting to further clarify the correlation between PON1 gene polymorphisms and breast cancer risk. Methods: After searches in the database such as MEDLINE, EBSCO, ProQuest, Google Scholar, High-Wire, SID (Scientific Informati...

  12. Vitamin D receptor gene polymorphisms and hepatocellular carcinoma in alcoholic cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Edmondo; Falleti; Davide; Bitetto; Carlo; Fabris; Annarosa; Cussigh; Elisabetta; Fontanini; Ezio; Fornasiere; Elisa; Fumolo; Sara; Bignulin; Sara; Cmet; Rosalba; Minisini; Mario; Pirisi; Pierluigi; Toniutto

    2010-01-01

    AIM: To assess the relationship between vitamin D re-ceptor (VDR) gene polymorphisms and the presence of hepatocellular carcinoma (HCC). METHODS: Two-hundred forty patients who underwent liver transplantation were studied. The etiologies of liver disease were hepatitis C (100 patients), hepatitis B (37) and alcoholic liver disease (103). A group of 236 healthy subjects served as controls. HCC in the explanted liver was detected in 80 patients. The following single nucle-otide gene polymorphisms of the VDR w...

  13. The prion-related protein (testis-specific) gene (PRNT) is highly polymorphic in Portuguese sheep.

    Science.gov (United States)

    Mesquita, P; Garcia, V; Marques, M R; Santos Silva, F; Oliveira Sousa, M C; Carolino, I; Pimenta, J; Fontes, C M G A; Horta, A E M; Prates, J A M; Pereira, R M

    2016-02-01

    The objective of this study was to search for polymorphisms in the ovine prion-related protein (testis-specific) gene (PRNT). Sampling included 567 sheep from eight Portuguese breeds. The PRNT gene-coding region was analyzed by single-strand conformation polymorphism and sequencing, allowing the identification of the first ovine PRNT polymorphisms, in codons 6, 38, 43 and 48: c.17C>T (p.Ser6Phe, which disrupts a consensus arginine-X-X-serine/threonine motif); c.112G>C (p.Gly38>Arg); c.129T>C and c.144A>G (synonymous) respectively. Polymorphisms in codons 6, 38 and 48 occur simultaneously in 50.6% of the animals, 38.8% presenting as heterozygous. To study the distribution of the polymorphism in codon 43, a restriction fragment length polymorphism analysis was performed. Polymorphic variant c.129C, identified in 89.8% of the animals with 32.8% presented as heterozygous, was considered the wild genotype in Portuguese sheep. Eight different haplotypes which have comparable distribution in all breeds were identified for the PRNT gene. In conclusion, the PRNT coding region is highly polymorphic in sheep, unlike the prion protein 2 dublet gene (PRND), in which we previously found only one synonymous substitution (c.78G>A), in codon 26. The absence or reduced number of PRND heterozygotes (c.78G>A) was significantly associated with three PRNT haplotypes (17C-112G-129T-144A,17CT-112GC-129CT-144AG and 17T-112C-129C-144G), and the only three animals found homozygous at c.78A had the 17C-112G-129C-144A PRNT haplotype. These results constitute evidence of an association between polymorphic variation in PRND and PRNT genes, as has already been observed for PRND and prion protein gene (PRNP). © 2015 Stichting International Foundation for Animal Genetics.

  14. The V109G polymorphism in the p27 gene is associated with endometriosis.

    Science.gov (United States)

    Camargo-Kosugi, Cíntia M; da Silva, Ismael D C G; Sato, Hélio; D'Amora, Paulo; Carvalho, Cristina V; Nogueira-de-Souza, Naiara C; Girão, Manoel J C B; Schor, Eduardo

    2009-08-01

    To investigate the prevalence of the p27 gene polymorphism in women with endometriosis. Transversal case-control study. Genomic DNA was extracted from cells collected from buccal swabs. The p27 V109G polymorphism was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Brazilian population. We analysed the 104 patients and 109 control subjects. The distribution of genotype and allele frequencies of p27 V109G polymorphism was significantly different between the endometriosis cases and healthy women (p=0.016 and 0.002). Women who had at least one mutated allele presented twofold chances for endometriosis development (OR=1.9; 95% CI, 1.120-3.343). The polymorphic variant at codon 109 of the p27 gene seems to be associated with higher risk of endometriosis development.

  15. Cloning and sequence analysis of IL-2, IL-4 and IFN-γ from Indian Dromedary camels (Camelus dromedarius).

    Science.gov (United States)

    Nagarajan, G; Swami, Shelesh Kumar; Ghorui, S K; Pathak, K M L; Singh, R K; Patil, N V

    2012-06-01

    The cDNAs of three cytokines, viz., IL-2, IL-4 and IFN-γ from Dromedary camels were amplified by PCR using Bactrian camel sequences and subsequently cloned for sequence analysis. Relationship based on amino acid sequences revealed that Dromedary camel IL-2 shared 99.5% and 99.3% identity at the nucleotide and amino acid levels with Bactrian camel IL-2. In the case of IL-4, the identity of Dromedary camel was 99.7% and 99.2% at the nucleotide and amino acid levels, respectively with that of Bactrian camel. The Dromedary camel IFN-γ shared 100% identity both at nucleotide and amino acid levels with Bactrian camel IFN-γ. Phylogenetic analysis based on amino acid sequences indicated the close relationship in these cytokine genes between the Dromedary camel and other camelids.

  16. Assessing the validity of asthma associations for eight candidate genes and age at diagnosis effects.

    Directory of Open Access Journals (Sweden)

    María Pino-Yanes

    Full Text Available BACKGROUND: Before the advent of genome-wide association studies (GWAS, ADAM33, ADRB2, CD14, MS4A2 (alias FCER1B, IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: We systematically evaluated 286 common single nucleotide polymorphisms (SNPs of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls. We found that variants at MS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition, in silico replication with GWAS data supported the association of IL4R. CONCLUSIONS/SIGNIFICANCE: Our results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found.

  17. 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.

  18. Polymorphisms in DNA repair genes XRCC2 and XRCC3 risk of gastric cancer in Turkey

    Directory of Open Access Journals (Sweden)

    İlhami Gok

    2014-09-01

    Full Text Available We studied the prevalence of polymorphisms in genes XRCC2 and XRCC3 in stomach cancer patients who lived in North Eastern Turkey. A total of 61 cancer patients and 78 controls were included in this study. Single nucleotide changes were studied in XRCC2 and XRCC3 genes at locus Arg188His and Thr241Met. Blood samples were taken from the patients and controls, and DNA was isolated. The regions of interest were amplified using a polymerase chain reaction method. After amplification, we used restriction enzymes (HphI and NcoI to digest the amplified product. Digested product was then run through gel electrophoresis. We identified changes in the nucleotides in these specific regions. It was found that the Arg188His polymorphism of the XRCC2 gene was about 39% (24 out of the 61 among cancer patients. However, only 15% (12 out of 78 of the control group indicated this polymorphism. We also observed that 18 of the 61 cancer patients (29% carried the Thr241Met polymorphism of the XRCC3 gene whereas 11 of the 78 (14% individuals in the control group had the polymorphism. Our results showed a significant difference in polymorphism ratios between the cancer patients and health control group for the regions of interest. This result clearly showed that these polymorphisms increase the risk of stomach cancer and might be a strong marker for early diagnosis of gastric cancer.

  19. Correlation between IL-6 gene polymorphisms and sepsis of Chinese Han population in Henan province

    Directory of Open Access Journals (Sweden)

    Meng-xuan YANG

    2011-01-01

    Full Text Available Objective To investigate the correlation between-572G/C and-174G/C polymorphism of IL-6 gene and sepsis of Chinese Han population in Henan province.Methods A population-based case-control study involving 99 patients with sepsis and 260 health volunteers(control was carried out.The-572C/G and-174G/C polymorphism of IL-6 gene was analyzed by polymerase chain reaction and restriction fragment-length polymorphism(PCR-RFLP technique.Results The genotype frequencies of all 359 cases were in Hardy-Weinberg equilibrium(P>0.05.No polymorphism was found in-174 site(GG genotype only,while alleles G,C and genotypes GG,GC,CC were found in-572 site,and no significant difference of allele frequency existed between patients and controls.Unconditional logistic regression analysis showed-G572C polymorphism was related to sepsis,the susceptibility to sepsis of patients with GG genotype was significantly higher than that of patients with CC genotype(OR=2.411,95% CI=1.045-5.562,P=0.039 after age and gender correction.Conclusions The-G572C polymorphism of IL-6 gene associates with sepsis,and the GG is the risk genotype of sepsis.There maybe no polymorphism in-G174C of IL-6 gene of Chinese Han population in Henan province.

  20. Association of duffy blood group gene polymorphisms with IL8 gene in chronic periodontitis.

    Science.gov (United States)

    Sippert, Emília Ângela; de Oliveira e Silva, Cléverson; Visentainer, Jeane Eliete Laguila; Sell, Ana Maria

    2013-01-01

    The antigens of the Duffy blood group system (DARC) act as a receptor for the interleukin IL-8. IL-8 plays an important role in the pathogenesis of chronic periodontitis due to its chemotactic properties on neutrophils. The aim of this study was to investigate a possible association of Duffy blood group gene polymorphisms with the -353T>A, -845T>C and -738T>A SNPs of the IL8 gene in chronic periodontitis. One hundred and twenty-four individuals with chronic periodontitis and 187 controls were enrolled. DNA was extracted using the salting-out method. The Duffy genotypes and IL8 gene promoter polymorphisms were investigated by PCR-RFLP. Statistical analyses were conducted using the Chi square test with Yates correction or Fisher's Exact Test, and the possibility of associations were evaluated by odds ratio with a 95% confidence interval. When analyzed separately, for the Duffy blood group system, differences in the genotype and allele frequencies were not observed between all the groups analyzed; and, in nonsmokers, the -845C allele (3.6% vs. 0.4%), -845TC genotype (7.3% vs. 0.7%) and the CTA haplotype (3.6% vs. 0.4%) were positively associated with chronic periodontitis. For the first time to our knowledge, the polymorphisms of erythroid DARC plus IL8 -353T>A SNPs were associated with chronic periodontitis in Brazilian individuals. In Afro-Brazilians patients, the FY*02N.01 with IL8 -353A SNP was associated with protection to chronic periodontitis.

  1. Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene x gender interaction.

    Science.gov (United States)

    Wang, Ke-Sheng; Wang, Liang; Liu, Xuefeng; Zeng, Min

    2013-12-01

    The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes.We hypothesized that HS6ST3 gene polymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity (P triglycerides in the Marshfield sample (P triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology.

  2. Osteoporosis and polymorphisms of osteoprotegerin gene in postmenopausal women – a pilot study

    Science.gov (United States)

    Grazio, Simeon; Kosovic, Pasezada; Uremovic, Melita; Nemcic, Tomislav; Bobic, Jasminka

    2016-01-01

    Objectives Osteoprotegerin (OPG) has an important role in bone remodeling, and it has been proposed that the OPG gene might be a candidate gene for osteoporosis predisposition. Several studies have already assessed the connection between OPG gene polymorphism and bone mineral density (BMD). In this study we wanted to analyze the association of two polymorphisms in the OPG gene with BMD and bone turnover markers in women with and without osteoporosis. Material and methods In 22 postmenopausal women with osteoporosis (aged 65.6 ±12.6) and 59 women without osteoporosis (aged 60.8 ±8.7) we analyzed the association of two polymorphisms in the OPG gene with BMD, measured by dual energy absorptiometry and with bone turnover markers (crosslaps and osteoprotegerin). A163G, G209A, T245G and G1181C polymorphisms were determined. Results No significant differences in age, anthropometry, number of fractures, osteocalcin and cross-laps were found between women with and without osteoporosis. Women with osteoporosis were significantly longer in postmenopause. Significantly more women with osteoporosis had AG polymorphism (p = 0.038) compared to women without osteoporosis, while no significant difference was found in prevalence of TT and GG polymorphism between patients with and without osteoporosis. No relationship was found between investigated polymorphism and bone turnover markers. A significant negative correlation between total hip BMD and crosslaps (p = 0.046) as well as between total hip T score and crosslaps (p = 0.044) was found in women without osteoporosis Conclusions Postmenopausal women with osteoporosis had AG polymorphism more frequently than women without osteoporosis. Our results indicate that A163G polymorphism could have an impact on higher bone loss in postmenopausal women. PMID:27407270

  3. Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival.

    Directory of Open Access Journals (Sweden)

    Kaspar René Nielsen

    Full Text Available Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment.We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin's lymphoma (B-NHL samples encompassing 216 diffuse large B cell lymphoma (DLBCL and 139 follicular lymphoma (FL and 307 controls. The effect of single genes and haplotypes were investigated and gene-expression analysis was applied for selected genes. Since interaction between risk genes can have a large impact on phenotype, two-way gene-gene interaction analysis was included.We found inherited SNPs in genes critical for inflammatory pathways; TLR9, IL4, TAP2, IL2RA, FCGR2A, TNFA, IL10RB, GALNT12, IL12A and IL1B were significantly associated with disease risk and SELE, IL1RN, TNFA, TAP2, MBL2, IL5, CX3CR1, CHI3L1 and IL12A were, associated with overall survival (OS in specific diagnostic entities of B-NHL. We discovered noteworthy interactions between DLBCL risk alleles on IL10 and IL4RA and FL risk alleles on IL4RA and IL4. In relation to OS, a highly significant interaction was observed in DLBCL for IL4RA (rs1805010 * IL10 (rs1800890 (HR = 0.11 (0.02-0.50. Finally, we explored the expression of risk genes from the gene-gene interaction analysis in normal B-cell subtypes showing a different expression of IL4RA, IL10, IL10RB genes supporting a pathogenetic effect of these interactions in the germinal center.The present findings support the importance of inflammatory genes in B-cell lymphomas. We found association between polymorphic sites in inflammatory response genes and risk as well as outcome in B-NHL and suggest an effect of gene-gene interactions during the stepwise oncogenesis.

  4. ASSOCIATION OF PARATHYROID HORMONE GENE POLYMORPHISM WITH BONE MINERAL DENSITY IN CHINESE WOMEN

    Institute of Scientific and Technical Information of China (English)

    李梅; 孟迅吾; 周学瀛; 邢小平; 余卫

    2003-01-01

    Objective. To investigate the distribution frequency of parathyroid hormone(PTH) gene polymorphism in healthy adults from Bejing area and to explore the association of PTH genotypes with bone mineral density (BMD). Methods. PTH gene polymorphism was detected in 270 subjects by polymerase chain reaction (PCR) and PCR/restriction fragment length polymorphism (PCR/RFLP). The digestion products of restriction enzyme Bst B1 were separated on 1% agarose gels. PTH genotypes were confirmed by DNA sequences analysis. BMD was measured by dual-energy X-ray absorptiometry (DEXA, DPX- L, Lunar). Results. Genotype frequencies of BB, Bb, bb were 73.7% , 25.9% and 0.4% respectively in Beijing adults( P0.05). Conclusion. PTH gene polymorphism is not associated with BMD in Chinese women. The further research to explore the genetic risk factors of osteoporosis should be committed.

  5. Polymorphism of the C-reactive protein gene is associated with mortality in bacteraemia.

    Science.gov (United States)

    Eklund, Carita; Huttunen, Reetta; Syrjänen, Jaana; Laine, Janne; Vuento, Risto; Hurme, Mikko

    2006-01-01

    C-reactive protein (CRP) is an important molecule in the defence against bacterial infections. To discover if variation in the CRP gene is associated with clinical outcome of bacteraemia, we investigated 147 microbiologically verified bacteraemia patients (mean age 59 y, range 19-93 y) and determined whether CRP -717A>G, +1059G>C or +1444C>T single nucleotide polymorphisms (SNPs) were associated with clinical outcome of bacteraemia and/or CRP concentration caused by Staphylococcus aureus, Streptococcus pneumoniae, beta-haemolytic streptococci or Escherichia coli. The patients were genotyped for CRP gene polymorphisms, CRP was measured and clinical outcomes were recorded. The CRP -717A>G, a promoter region polymorphism was strongly associated with mortality from Streptococcus pneumoniae but did not correlate with plasma CRP concentration. These results suggest that mortality from Streptococcus pneumoniae may be associated with polymorphism of the promoter region of the CRP gene.

  6. POLYMORPHISM OF ANGIOTENSIN Ⅱ TYPE 1 RECEPTOR GENE IN ELDERLY PATIENTS WITH ESSENTIAL HYPERTENSION

    Institute of Scientific and Technical Information of China (English)

    方宁远; 张怡; 陆惠华; 郑迪辉; 邬亦贤; 郑道声

    2003-01-01

    Objective To detect the A/C1166 polymorphism of angiotensin Ⅱ type-1 receptor (AT1 R) gene in essential hypertensive elderly.MethodsThe A/C1166 polymorphism of AT1 R gene was assessed by polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) in a case control study of 87 essential hypertensive elders (EH) and 55 normotensive elders (NT).ResultsThe genotype frequencies of AA, AC, CC were 0.805, 0.161, 0.034 in EH group and 0.927, 0.073, 0.000 in NT group respectively. The frequency of C1166 allele was higher in EH group (0.115) than in NT group (0.036)(P<0.05).ConclusionThe results indicate that A/C1166 polymorphism of AT1 R gene may be associated with essential hypertension in elderly.

  7. Tyrosine Kinase Domain Gene Polymorphism of Epidermal Growth Factor Receptor in Gastric Cancer in Northern Iran

    Directory of Open Access Journals (Sweden)

    Jeivad F

    2012-01-01

    Full Text Available Background: Gastric cancer is one of the most common diseases of digestive system with a low 5-year survival rate and metastasis is the main cause of death. Multi-factors, such as changes in molecular pathways and deregulation of cells are involved in the disease development. Epidermal growth factor receptor pathway (EGFR which is associated with cell proliferation and survival can influence cancer development. EGFR function is governed by its genetic polymorphism; thus, we aimed to study the tyrosine kinase domain gene mutations of the receptor in patients with gastric cancer.Methods : In this experimental study, 123 subjects (83 patients with gastric cancer and 40 normal subjects were investigated in north of Iran for EGFR gene polymorphisms during 1 year. Genomic DNA was extracted by DNA extraction kit according to the manufacture's protocol. Polymerase chain reaction single-stranded conformation polymorphism (PCR-SSCP and silver staining were performed for investigating EGFR gene polymorphisms. Results : The participants included 72 men and 44 women. Gene polymorphism in exon 18 was present in 10% of the study population but SSCP pattern in exon 19 did not show different migrate bands neither in patients nor in normal subjects.Conclusion: It seems that screening for tyrosine kinas gene polymorphism of epidermal growth factor receptor in patients with gastric cancer and use of tyrosine kinas inhibitors could be useful in the prevention of disease progress and improvement of treatment process for a better quality of life in these patients.

  8. Cytochrome P450c17alpha (CYP17 gene polymorphism is not associated with leiomyoma susceptibility

    Directory of Open Access Journals (Sweden)

    Hsieh Yao-Yuan

    2002-01-01

    Full Text Available Estrogen plays a role in the pathogenesis of leiomyoma. The CYP17 gene codes for the cytochrome P450c17alpha enzyme, which is involved in the biosynthesis of estrogen. Our aim was to investigate if CYP17 polymorphism could be a useful marker to predict the susceptibility to leiomyoma. Our sample of female subjects was divided into two groups: (1 with leiomyoma (n = 159; (2 without leiomyoma (n = 128. A 169-bp fragment encompassing the A1/A2 polymorphic site of the CYP17 gene was amplified by polymerase chain reaction (PCR, restricted by enzyme MspA1I and electrophored on agarose gel. Genotypes and allelic frequencies for this polymorphism in both groups were compared. There was no significant difference between the two groups regarding the distribution of the CYP17 gene polymorphism frequencies. The A1 homozygote/heterozygote/A2 homozygote proportions for CYP17 in both groups were: (1 17.0/46.5/36.5%, and (2 17.2/45.3/37.5%. The proportions for alleles A1 and A2 were also comparable in the two groups. A1 and A2 allele frequencies were: 7% (40.3/59 in group 1, and 2% (39.8/60 in group 2. No significant association was observed between the risk of leiomyoma and polymorphisms of the CYP 17 gene. So, CYP17 gene polymorphism does not appear to be a useful marker for the prediction of leiomyoma susceptibility.

  9. Common Oxytocin Receptor Gene Polymorphisms and the Risk for Preterm Birth

    Directory of Open Access Journals (Sweden)

    Lorenz Kuessel

    2013-01-01

    Full Text Available Oxytocin is crucially involved in the onset and maintenance of labor. We investigated the association between oxytocin receptor gene polymorphisms and preterm birth. The presence of four common oxytocin receptor gene polymorphisms (rs2254298, rs53576, rs2228485 and rs237911 was evaluated in one hundred women with preterm birth and one hundred healthy women using restriction fragment length polymorphism genotyping. No association was found between the presence of any individual oxytocin receptor gene polymorphism and preterm birth. In haplotype analysis, the haplotype combination of rs2254298 A allele, rs2228485 C allele and rs237911 G allele was found to be significantly associated with an increased risk of preterm birth (OR = 3.2 [CI 1.04–9.8], p = 0.043. In conclusion our findings suggest that a combination of three oxytocin receptor gene polymorphisms is associated with an increased risk for preterm birth. We propose further studies investigating the role of oxytocin receptor gene polymorphisms and preterm birth.

  10. Changes in plasma IL4, TNF-α and CRP in response to regular ...

    African Journals Online (AJOL)

    Administrator

    Objective: To determine effects of passive smoking on plasma IL4, TNFá, and CRP in ... Plasma CRP, IL4 and TNFá were measured using commercially available ELISA kits. ..... with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 1996;153:530- ... Bronchial Hyperresponsiveness, and Atopy.

  11. NanoUPLC-MS(E) proteomic analysis of osteoclastogenesis downregulation by IL-4.

    Science.gov (United States)

    Freire, Mirna S; Cantuária, Ana Paula C; Lima, Stella M F; Almeida, Jeeser A; Murad, André M; Franco, Octavio L; Rezende, Taia M B

    2016-01-10

    Bone resorption is an important factor in bone homeostasis and imbalance can cause several diseases. In osteoimmunology, IL-4 has been described as an important factor in promoting M2 macrophage profile. In order to shed some light on the effect of IL-4 on osteoclast precursors in the presence of RANKL, cytokines and nitric oxide (NO) production and the proteomic profile were analyzed. The presence of IL-4 in in vitro osteoclastogenesis provides production of TNF-α, IL-1α, IL-1β, IL-10 and IL-12 at basal cell levels. Regarding NO production, IL-4 was sufficient to increase the basal NO levels. Proteomic analyses identified 877 global proteins. IL-4 in in vitro RANKL-mediated osteoclastogenesis leads to the expression of 118 proteins. The presence of rIL-4 in in vitro rRANKL-mediated-osteoclastogenesis downregulated this process. However, the proteomics findings in the osteoclastogenesis demonstrated a much greater effect on osteoclast precursor cells than on RANKL-differentiated osteoclasts. These results suggest that the main effect of IL-4 in pre-osteoclast cells leads to a M2 macrophage activation, and this probably contributed to a reduction in osteoclastogenesis when both stimuli were used. This study noticed that IL-4 plays an important regulatory role in bone homeostasis due to its suppressive potential of precursor osteoclast cells.

  12. Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene × gender interaction

    Indian Academy of Sciences (India)

    Ke-Sheng Wang; Liang Wang; Xuefeng Liu; Min Zeng

    2013-12-01

    The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes. We hypothesized that HS6ST3 gene polymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity $(P \\lt 0.05)$. SNP rs535812 revealed a stronger association with obesity in meta-analysis of these two samples $(P = 0.0105)$. The T–A haplotype from rs878950 and rs9525149 revealed significant association with obesity in the Marshfield sample $(P = 0.012)$. Moreover, nine SNPs showed associations with triglycerides in the Marshfield sample $(P \\lt 0.05)$ and the best signal was rs1927796 $(P = 0.00858)$. In addition, rs7331762 showed a strong gene × gender interaction $(P = 0.00956)$ for obesity while rs1927796 showed a strong gene × gender interaction $(P = 0.000625)$ for triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology.

  13. (MTHFR) gene polymorphism is associated with abortion in Chinese ...

    African Journals Online (AJOL)

    Administrator

    2011-10-19

    Oct 19, 2011 ... association between MTHFR polymorphism and cow abortion is scarce. .... days after AI. (Pierson and Ginther, 1984) with a portable ultrasound scanner and ... inseminated in the same lactation after pregnancy (Committee,.

  14. Contrasting genetic influence of PON 1 coding gene polymorphisms ...

    African Journals Online (AJOL)

    Nadia Youssef Sadek Morcos

    2015-03-31

    Mar 31, 2015 ... c Toxicity Department, Poison Control Center, Ain Shams Universty Hospital, Egypt ... frequency distribution of PON1 Q192R polymorphism showed a highly ... at position 192, where either glutamine (Q) or arginine (R).

  15. Detection of polymorphisms in leptin gene using single strand ...

    African Journals Online (AJOL)

    student

    in the entire population to develop single nucleotide polymorphisms (SNPs) for association studies with different .... electrophoresis was carried out in a Bio Rad Protean II xi vertical .... Rapid and sensitive detection of point mutations and.

  16. Association of sweet taste receptor gene polymorphisms with dental caries experience in school children.

    Science.gov (United States)

    Haznedaroğlu, Eda; Koldemir-Gündüz, Meliha; Bakır-Coşkun, Nur; Bozkuş, Hasan M; Çağatay, Penbe; Süsleyici-Duman, Belgin; Menteş, Ali

    2015-01-01

    Sweet taste is a powerful factor influencing food acceptance. The peripheral taste response to sugar is mediated by the TAS1R2/TAS1R3 taste receptors. The aim of the study was to determine the relationship between TAS1R2 (rs35874116 or rs9701796) and/or TAS1R3 (rs307355) single nucleotide polymorphisms with dental caries experience in schoolchildren. A total of 184 schoolchildren aged between 7 and 12 years (101 girls, 83 boys) were included in the study. Genomic DNA was extracted from saliva samples and the genotypes were identified by qPCR. The genotype frequencies were as follows: 6.6% for homozygous wild type, 41.8% for heterozygous and 51.6% for homozygous polymorphic genotype carriers of TAS1R2 gene rs35874116; 27.8% for heterozygous and 72.2% for homozygous polymorphic genotype carriers of TAS1R2 gene rs9701796, and 83.1% for homozygous wild type and 16.9% for heterozygous genotype carriers of TAS1R3 gene rs307355 polymorphism. A significant association was observed between total caries experience (dft + DMFT - decayed filled primary teeth + decayed, missing and filled permanent teeth) and TAS1R2 rs35874116 (p = 0.008) and TAS1R3 rs307355 (p = 0.04) gene polymorphisms but not for TAS1R2 gene rs9701796 polymorphism. TAS1R3 gene rs307355 polymorphism has been found to be an independent risk factor for dental caries experience by logistic regression analysis and to have increased the risk of caries. Moderate caries experience (4-7 caries) was found to be associated with TAS1R3 rs307355 heterozygous genotype, whereas high-risk caries experience (>8 caries) was found to be associated with TAS1R2 rs35874116 homozygous polymorphic genotype.

  17. Estrogen Receptor Gene (ESR1 PVUII and XBAI Polymorphisms and Bone Mineral Density in Kazakh Women

    Directory of Open Access Journals (Sweden)

    Ainur Akilzhanova

    2014-01-01

    Full Text Available Introduction: Osteoporosis is a common age-related disease that is strongly influenced by genetics. Polymorphisms of the estrogen receptor gene alpha (ESR1 are consistently been associated with bone mineral density (BMD and fracture. The purpose of this investigation was to evaluate potential association of single nucleotide polymorphism (SNP variants of the ESR1 gene and bone mineral density (BMD of the lumbar spine in Kazakh women. Methods: 140 female participants in Pavlodar clinics with varying measures of BMD. We are examined the potential association of BMD with 2 SNPs from the ESR1 gene (rs2234693 [PvuII] and rs9340799 [XbaI]. Genotyping of the PvuII and XbaI polymorphisms was performed by direct sequencing of the gene fragments containing restriction sites with the identification of genotypes PP, Pp, pp and XX, Xx, xx respectively. Results: Unadjusted mean BMD values ranged from 1.14±0.14 g/cm2 in Caucasian women and 1.03±0.11 g/cm2 in Asian women. The association between PvuII polymorphism and BMD at the lumbar spine (p= 0.04 for PP=Pp=pp was statistically significant in all women. The XbaI polymorphism was not associated with BMD at lumbar spine. The relative risk for low BMD was higher for the marker PvuII (RR=1.51 than for the marker XbaI (RR=1.35. Conclusion: The PvuII polymorphism had a weak association with lumbar spine BMD.  XbaI polymorphism was unlikely to be a predictor of lumbar spine BMD in Kazakh women. These conclusions could help to determine the genetic risk factors for osteoporosis; however, further studies on the association between gene polymorphisms and BMD are needed including larger numbers of participants and genes to clarify genetic risks.

  18. Association of gender, ABCA1 gene polymorphisms and lipid profile in Greek young nurses

    Directory of Open Access Journals (Sweden)

    Kolovou Vana

    2012-07-01

    Full Text Available Abstract Objective One of the important proteins involved in lipid metabolism is the ATP-binding cassette transporter A1 (ABCA1 encoding by ABCA1 gene. In this study we evaluated the single nucleotide polymorphisms (SNPs of ABCA1 gene. We analyzed SNPs in chromosome 9 such as rs2230806 (R219K in the position 107620867, rs2230808 (R1587K in the position 106602625 and rs4149313 (I883M in the position 106626574 according to gender and lipid profile of Greek nurses. Methods The study population consisted of 447 (87 men unrelated nurses who were genotyped for ABCA1 gene polymorphisms. Additionally, lipid profile [total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDL-C and apolipoprotein A1] was evaluated. Results The distribution of all three studied ABCA1 gene polymorphisms did not differ according to gender. However, only R219K genotype distribution bared borderline statistical significance (p = 0.08 between the two studied groups. Moreover, allele frequencies of R219K, R1587K and I88M polymorphisms did not differ according to gender. In general, blood lipid levels did not seem to vary according to ABCA1 gene polymorphisms, when testing all subjects or when testing only men or only women. However, a significant difference of LDL-C distribution was detected in all subjects according to R1587K genotype, indicating lower LDL-C levels with KK polymorphism (p = 0.0025. The above difference was solely detected on female population (p = 0.0053. Conclusions The ABCA1 gene polymorphisms frequency, distribution and lipid profile did not differ according to gender. However, in the female population the KK genotype of R1587K gene indicated lower LDL-C levels. Further studies, involving a higher number of individuals, are required to clarify genes and gender contribution.

  19. Polymorphisms of the DNA repair genes XRCC1 and XRCC3 in a Brazilian population

    Directory of Open Access Journals (Sweden)

    Duarte Márcia Cristina

    2005-01-01

    Full Text Available In several DNA repair genes, polymorphisms may result in reduced repair capacity, which has been implicated as a risk factor for various types of cancer. The frequency of the polymorphic alleles varies among populations, suggesting an ethnic distribution of genotypes. We genotyped 300 healthy Southeastern Brazilian individuals (262 of European ancestry and 38 of African ancestry for polymorphisms of codons 194 and 399 of the XRCC1 base excision repair pathway gene and of codon 241 of the XRCC3 homologous recombination repair pathway gene. The allele frequencies were 0.07 for the Arg194Trp and 0.33 for the Arg399Gln codons of the XRCC1 gene and 0.35 for the Thr241Met codon of the XRCC3 gene. The genotypic frequencies were within Hardy-Weinberg equilibrium. These frequencies showed ethnic variability when compared with those obtained for different populations from several countries.

  20. Gene polymorphisms of renin-angiotensin-aldosterone system components and the progression of chronic kidney diseases

    Directory of Open Access Journals (Sweden)

    Agata Kujawa-Szewieczek

    2010-08-01

    Full Text Available The renin-angiotensin-aldosterone system (RAAS plays an important role in the pathogenesis of hypertension as well as cardiovascular diseases and chronic kidney diseases. Among the most frequently studied RAAS gene polymorphisms are the angiotensin-converting enzyme insertion/deletion (I/D, angiotensinogen M235T and angiotensin II receptor type 1 A1166C polymorphisms.A significant correlation was found between the I/D polymorphism and cardiovascular morbidity and mortality rates. However, there was no significant correlation between I/D, M235T, A1166C polymorphism and arterial hypertension. The role of I/D polymorphism in the development and progression of chronic kidney disease is also non-conclusive. However, DD genotype has been identified as relevant for loss of renal function both in patients with IgA nephropathy and in patients of Asian origin with diabetic nephropathy.The relationship between RAAS gene polymorphism and transplanted kidney function has not been confirmed in large prospective and retrospective studies. Conclusion: there is no clear opinion concerning the influence of RAAS genotypes on the prevalence of post-transplant hypertension or erythrocytosis.Although a role of RAAS gene polymorphism in kidney function deterioration could not be ruled out, it is more likely that a variety of genetic and environmental factors influence the progression of chronic kidney diseases.

  1. Association of TAP Gene Polymorphisms and Risk of Cervical Intraepithelial Neoplasia

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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, P10(-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.

  3. Interaction between endothelial cells and the secreted cytokine drives the fate of an IL4- or an IL5-transduced tumour.

    Science.gov (United States)

    Di Carlo, E; Modesti, A; Coletti, A; Colombo, M P; Giovarelli, M; Forni, G; Diodoro, M G; Musiani, P

    1998-12-01

    Injection of interleukin-4 (IL4) gene-transduced tumour cells into syngeneic immunocompetent mice resulted in tumour rejection in which a key role for eosinophils was suggested. To evaluate whether IL5 inhibits tumour growth by selectively inducing eosinophil recruitment and activation, a poorly differentiated mammary adenocarcinoma cell line (TSA) was transfected with the IL5 gene and the cells secreting IL5 (TSA-IL5) were injected subcutaneously (s.c.) in syngeneic mice. The oncogenicity of TSA-IL5 was compared with that exhibited by TSA cells transfected with the IL4 gene (TSA-IL4) and with the neomycin resistance gene only (TSA-neo). At progressive times after subcutaneous challenge, tumour growth areas were studied histologically, ultrastructurally, and immunohistochemically to identify the reactive cells, visualize tumour vessels, and detect the cytokines and chemokines involved in the anti-tumour reaction. Both the morphological and the functional data showed that TSA-IL5, despite the large eosinophil infiltrate, grew progressively like TSA-neo, suggesting that eosinophils per se do not play a crucial role in TSA tumour rejection. Furthermore, our data indicate that the rejection of TSA-IL4 depends on the IL4-induced expression of VCAM-1 and MCP-1 by endothelial cells. MCP-1 together with VCAM-1 results in recruitment and activation of basophils, mast cells, and macrophages, and hence a pro-inflammatory cytokine cascade that initially favours the influx and activation of neutrophils and finally tumour rejection. In this context, the rejection of TSA-IL4 seems to involve a variety of reactive cells and rests on a continuous cross-talk between basophils, mast cells, macrophages, CD8-positive lymphocytes, and granulocyte subsets, mostly neutrophils.

  4. XRCC1 gene polymorphisms and risk of ameloblastoma.

    Science.gov (United States)

    Yanatatsaneejit, Pattamawadee; Boonsuwan, Titiporn; Mutirangura, Apiwat; Kitkumthorn, Nakarin

    2013-06-01

    Ameloblastoma is a common benign odontogenic tumour with inherently aggressive behaviour. Genetic susceptibility of single nucleotide polymorphism (SNP) can likely predict ameloblastoma at risk patients but this data remains limited. Here, we studied XRCC1 polymorphism as a risk factor for ameloblastoma. Eighty-two ameloblastoma samples and blood from 140 healthy controls were used to perform polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for XRCC1 at codons 194, 280 and 399, and confirmed by sequence analysis. Compare to healthy control, a significant increase was noted in the occurrence of polymorphism at codon 194 and 399 in ameloblastoma patients. At codon 194, tryptophan encoded by T, was the susceptibility allele showed an ODD ratio of (95% CI)=1.62 (1.05-2.48), p=0.027. At codon 399, glycine encoded by A was the susceptibility allele showing ODD ratio of (95% CI)=1.83 (1.19-2.84), p=0.005. Moreover at codon 399, we found AG as the susceptibility genotype (2.06 (1.14-3.72), p=0.015). However, we did not find any significant increase in polymorphic occurrence in ameloblastoma patients at codon 280. For haplotype analysis of 3 codons, we found GGC as protective haplotype, and AGT as the risk haplotype. Our data suggest that polymorphism at codons 194 and 399, likely contributes to the risk of developing ameloblastoma. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. IL-4、IL-13蛋白表达及抗IL-4、IL-13人源单链抗体的筛选%Expression of IL-4 and IL-13 proteins and selection of scFvs against IL-4 and IL-13

    Institute of Scientific and Technical Information of China (English)

    袁青; 黄黎; 郭夕源; 叶迎春; 年四季

    2013-01-01

    Objective:Expression of IL-4 and IL-13 proteins and selection of human scFvs against IL-4 and IL-13 by phage display.Methods:The mRNA of PBMC from healthy volunteer was extracted and cDNA of IL-4 and IL-13 were synthesized by RT-PCR,and the proteins of IL-4 and IL-13 were expressed and identified.The scFvs against IL-4 and IL-13 were selected from a non-immune human scFvs library by phage display with biotinylation IL-4 and IL-13 protein.Results:The size of cDNA of amplified IL-4 was 280 bp,and that of expressed fusion protein was about 27 kD.The size of cDNA of amplified IL-13 was 252 bp,and that of expressed fusion protein was about 25 kD.The human scFvs library was screened for three rounds by ribosome display,and about 37% scFvs has binding activities with IL-4 and about 27% scFvs has binding activities with IL-13.Four scFvs with good binding activities with IL-4 or IL-13 were selected and identified by Western blot.Conclusion:The scFvs against IL-4 and against IL-13 were selected successfully.%目的:表达IL-4和IL-13蛋白,从人源单链抗体文库中分别筛选抗IL-4和抗IL-13单链抗体.方法:采用RT-PCR从健康志愿者外周血单核细胞(PBMC) mRNA中扩增IL-4和IL-13 cDNA;构建硫氧还蛋白融合表达载体,转化大肠杆菌BL21,IPTG诱导表达并对表达产物进行纯化鉴定.以生物素化的IL-4和IL-13为抗原从前期构建的人源抗体文库中采用噬菌体展示技术分别筛选抗IL-4和抗IL-13人源单链抗体(scFv).结果:扩增的IL-4 cDNA大小为280 bp,表达的融合蛋白大小为27 kD左右.扩增的IL-13 cDNA大小为252 bp,表达的融合蛋白大小为25 kD左右.分别以生物素化的IL-4和IL-13蛋白为抗原,采用噬菌体展示技术对人源抗体文库进行3轮富集后,分别有大约37%的scFvs与IL-4有结合特性,有约27%的scFvs与IL-13有结合特性.筛选了4株分别与IL-4和IL-13结合能力强的单链抗体进行了Westem blot鉴定和测序.结论:成功筛选到抗IL-4

  6. Polymorphism Interaction Analysis (PIA: a method for investigating complex gene-gene interactions

    Directory of Open Access Journals (Sweden)

    Chanock Stephen J

    2008-03-01

    Full Text Available Abstract Background The risk of common diseases is likely determined by the complex interplay between environmental and genetic factors, including single nucleotide polymorphisms (SNPs. Traditional methods of data analysis are poorly suited for detecting complex interactions due to sparseness of data in high dimensions, which often occurs when data are available for a large number of SNPs for a relatively small number of samples. Validation of associations observed using multiple methods should be implemented to minimize likelihood of false-positive associations. Moreover, high-throughput genotyping methods allow investigators to genotype thousands of SNPs at one time. Investigating associations for each individual SNP or interactions between SNPs using traditional approaches is inefficient and prone to false positives. Results We developed the Polymorphism Interaction Analysis tool (PIA version 2.0 to include different approaches for ranking and scoring SNP combinations, to account for imbalances between case and control ratios, stratify on particular factors, and examine associations of user-defined pathways (based on SNP or gene with case status. PIA v. 2.0 detected 2-SNP interactions as the highest ranking model 77% of the time, using simulated data sets of genetic models of interaction (minor allele frequency = 0.2; heritability = 0.01; N = 1600 generated previously [Velez DR, White BC, Motsinger AA, Bush WS, Ritchie MD, Williams SM, Moore JH: A balanced accuracy function for epistasis modeling in imbalanced datasets using multifactor dimensionality reduction. Genet Epidemiol 2007, 31:306–315.]. Interacting SNPs were detected in both balanced (20 SNPs and imbalanced data (case:control 1:2 and 1:4, 10 SNPs in the context of non-interacting SNPs. Conclusion PIA v. 2.0 is a useful tool for exploring gene*gene or gene*environment interactions and identifying a small number of putative associations which may be investigated further using other

  7. Oxytocin Receptor Gene Polymorphisms in Patients With Diabetes

    Directory of Open Access Journals (Sweden)

    Saravani

    2015-04-01

    Full Text Available Background Type 2 Diabetes (T2D is a chronic metabolic disease associated with increased mortality and morbidity. High levels of glucose can damage organs, such as the kidneys, eyes and nerves. Oxytocin (OXT can regulate feeding behavior, energy balance, insulin sensitivity and insulin secretion. The OXT Receptor (OXTR mediates the action of OXT on cells. The role of OXTR polymorphism in carbohydrate metabolism disorders, especially in T2D, is not clear. Objectives The current study aimed to investigate the possible associations between OXTR polymorphism and the risk of developing T2D. Patients and Methods To study genetic polymorphisms, 120 patients with T2D and 120 controls were selected. Genotyping of the OXTR rs53576 and rs2254298 variants was performed using allele-specific Polymerase Chain Reaction (PCR and Restriction Fragment Length Polymorphism (RFLP PCR, respectively. Data were analyzed using Chi-square analysis and logistic regression. Results The logistic regression analysis suggested no significant associations of OXTR Single Nucleotide Polymorphism (SNP rs22542987 in genotypes (OR = 1.054, 95% CI: 0.557 - 1.995, P = 0.871 and alleles of patients with T2D in the study population (OR = 1.004, 95% CI: 0.547 - 1.845, P = 1. The rs53576 polymorphism showed the TT genotype (OR = 0.466, %95CI: 0.22 - 0.94, P = 0.035, as well as T allele (OR = 0.66, %95 CI: (0.46 - 0.95, P = 0.03 in the patients and control group with a significant difference suggesting the protective role this polymorphism plays in T2D. Conclusions Our findings showed that the genotype TT rs53576 OXTR, as well as T allele had significant differences in our population and play a protective role. Therefore, it is suggested to place more interest on these OXTR in large populations and different ethnic groups.

  8. Polymorphism of the prion protein gene (PRNP) in Polish cattle affected by classical bovine spongiform encephalopathy.

    Science.gov (United States)

    Gurgul, Artur; Czarnik, Urszula; Urszula, Czarnik; Larska, Magdalena; Polak, Mirosław P; Strychalski, Janusz; Słota, Ewa

    2012-05-01

    Recent attempts to discover genetic factors affecting cattle resistance/susceptibility to bovine spongiform encephalopathy (BSE) have led to the identification of two insertion/deletion (indel) polymorphisms, located within the promoter and intron 1 of the prion protein gene PRNP, showing a significant association with the occurrence of classical form of the disease. Because the effect of the polymorphisms was studied only in few populations, in this study we investigated whether previously described association of PRNP indel polymorphisms with BSE susceptibility in cattle is also present in Polish cattle population. We found a significant relation between the investigated PRNP indel polymorphisms (23 and 12 bp indels), and susceptibility of Polish Holstein-Friesian cattle to classical BSE (P < 0.05). The deletion variants of both polymorphisms were related to increased susceptibility, whereas insertion variants were protective against BSE.

  9. Association of inflammatory gene polymorphisms and conventional risk factors with arterial stiffness by age.

    Science.gov (United States)

    Kheradmand, Motahare; Niimura, Hideshi; Kuwabara, Kazuyo; Nakahata, Noriko; Nakamura, Akihiko; Ogawa, Shin; Mantjoro, Eva Mariane; Shimatani, Keiichi; Nerome, Yasuhito; Owaki, Tetsuhiro; Kusano, Ken; Takezaki, Toshiro

    2013-01-01

    Inflammatory gene polymorphisms are potentially associated with atherosclerosis risk, but their age-related effects are unclear. To investigate the age-related effects of inflammatory gene polymorphisms on arterial stiffness, we conducted cross-sectional and 5-year follow-up studies using the cardio-ankle vascular index (CAVI) as a surrogate marker of arterial stiffness. We recruited 1850 adults aged 34 to 69 years from the Japanese general population. Inflammatory gene polymorphisms were selected from NF-kB1, CD14, IL-6, IL-10, MCP-1, ICAM-1, and TNF-α. Associations of CAVI with genetic and conventional risk factors were estimated by sex and age group (34-49, 50-59, and 60-69 years) using a general linear model. The association with 5-year change in CAVI was examined longitudinally. Glucose intolerance was associated with high CAVI among women in all age groups, while hypertension was associated with high CAVI among participants in all age groups, except younger women. Mean CAVI for the CD14 CC genotype was lower than those for the TT and CT genotypes (P for trend = 0.005), while the CD14 polymorphism was associated with CAVI only among men aged 34 to 49 years (P = 0.006). No association of the other 6 polymorphisms with CAVI was observed. No association with 5-year change in CAVI was apparent. Inflammatory gene polymorphisms were not associated with arterial stiffness. To confirm these results, further large-scale prospective studies are warranted.

  10. Risk conferred by FokI polymorphism of vitamin D receptor (VDR gene for essential hypertension

    Directory of Open Access Journals (Sweden)

    N Swapna

    2011-01-01

    Full Text Available Background : The vitamin D receptor (VDR gene serves as a good candidate gene for susceptibility to several diseases. The gene has a critical role in regulating the renin-angiotensin system (RAS influencing the regulation of blood pressure. Hence determining the association of VDR polymorphisms with essential hypertension is expected to help in the evaluation of risk for the condition. Aim : The aim of this study was to evaluate association between VDR Fok I polymorphism and genetic susceptibility to essential hypertension. Materials and Methods : Two hundred and eighty clinically diagnosed hypertensive patients and 200 normotensive healthy controls were analyzed for Fok I (T/C [rs2228570] polymorphism by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP analysis. Genotype distribution and allele frequencies in patients and controls, and odds ratios (ORs were calculated to predict the risk for developing hypertension by the individuals of different genotypes. Results : The genotype distribution and allele frequencies of Fok I (T/C [rs2228570] VDR polymorphism differed significantly between patients and controls (χ2 of 18.0; 2 degrees of freedom; P = 0.000. FF genotype and allele F were at significantly greater risk for developing hypertension and the risk was elevated for both the sexes, cases with positive family history and habit of smoking. Conclusions : Our data suggest that VDR gene Fok I polymorphism is associated with the risk of developing essential hypertension

  11. IL-4 protects the B-cell lymphoma cell line CH31 from anti-IgM-induced growth arrest and apoptosis:contribution of the PI-3' kinase/AKT pathway

    Institute of Scientific and Technical Information of China (English)

    Gregory B Carey; Elena Semenova; Xiulan Qi; Achsah D Keegan

    2007-01-01

    Interleukin-4(IL-4)promotes lymphocyte survival and protects primary lymphomas from apoptosis.Previous studies reported differential requirements for the signal transducer and activator of transcription 6(STAT6)and IRS2/phosphatidylinositol 3 kinase(PI-3K)signaling pathways in mediating the IL-4-induced protection from Fas-mediated apoptosis.In this study,we characterized IL-4-activated signals that suppress anti-IgM-mediated apoptosis and growth arrest of CH31,a model B-cell lymphoma line.In CH31,anti-IgM treatment leads to the loss of mitochondrial membrane potential,phospho-Akt,phospho-CDK2,and c-myc protein.These losses are followed by massive induction ofp27Kip1 protein expression,cell cycle arrest,and apoptosis.Strikingly,IL-4 treatment prevented or reversed these changes.Furthermore,IL-4 suppressed the activation of caspases 9 and 3,and,in contrast to previous reports,induced the phosphorylation(deactivation)of BAD.IL-4 treatment also induced expression of BclxL,a STAT6-dependent gene.Pharmacologic inhibitors and dominant inhibitory forms of PI-3K andAkt abrogated the anti-apoptotic function of IL-4.These results suggest that the IL-4 receptor activates several signaling pathways,with the Akt pathway playing a major role in suppression of the apoptotic program activated by anti-IgM.

  12. Interleukin-17 Gene Polymorphisms Contribute to Cancer Risk

    Directory of Open Access Journals (Sweden)

    Yu-Ming Niu

    2014-01-01

    Full Text Available Epidemiological studies have suggested that interleukin-17 (IL-17 polymorphisms are associated with cancer risk. However, the results of these studies are inconsistent. Therefore, we performed a meta-analysis to obtain a precise conclusion. Odds ratios (ORs with 95% confidence intervals (CIs were used to assess the association of the IL-17A rs2275913G>A and IL-17F rs763780T>C polymorphisms with cancer risk. Publication bias and sensitivity analyses were performed to ensure the statistical power. Overall, 10 relevant case-control studies involving 4,516 cases and 5,645 controls were included. The pooled ORs with 95% CIs indicated that the IL-17A rs2275913G>A polymorphism was significantly associated with increased cancer risk (for A versus G: OR = 1.28, 95% CI: 1.16–1.41, PC polymorphism was also significantly associated with gastric cancer development. Overall, the present meta-analysis suggests that IL-17 polymorphisms increase the risk of developing cancer, particularly gastric cancer, in the Asian (and Chinese population.

  13. Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites

    Directory of Open Access Journals (Sweden)

    Rockett Kirk

    2011-08-01

    Full Text Available Abstract Background Resistance to anti-malarial drugs is a widespread problem for control programmes for this devastating disease. Molecular tests are available for many anti-malarial drugs and are useful tools for the surveillance of drug resistance. However, the correlation of treatment outcome and molecular tests with particular parasite markers is not perfect, due in part to individuals who are able to clear genotypically drug-resistant parasites. This study aimed to identify molecular markers in the human genome that correlate with the clearance of malaria parasites after drug treatment, despite the drug resistance profile of the protozoan as predicted by molecular approaches. Methods 3721 samples from five African countries, which were known to contain genotypically drug resistant parasites, were analysed. These parasites were collected from patients who subsequently failed to clear their infection following drug treatment, as expected, but also from patients who successfully cleared their infections with drug-resistant parasites. 67 human polymorphisms (SNPs on 17 chromosomes were analysed using Sequenom's mass spectrometry iPLEX gold platform, to identify regions of the human genome, which contribute to enhanced clearance of drug resistant parasites. Results An analysis of all data from the five countries revealed significant associations between the phenotype of ability to clear drug-resistant Plasmodium falciparum infection and human immune response loci common to all populations. Overall, three SNPs showed a significant association with clearance of drug-resistant parasites with odds ratios of 0.76 for SNP rs2706384 (95% CI 0.71-0.92, P = 0.005, 0.66 for SNP rs1805015 (95% CI 0.45-0.97, P = 0.03, and 0.67 for SNP rs1128127 (95% CI 0.45-0.99, P = 0.05, after adjustment for possible confounding factors. The first two SNPs (rs2706384 and rs1805015 are within loci involved in pro-inflammatory (interferon-gamma and anti-inflammatory (IL-4

  14. Association between CYP1B1 Gene Polymorphisms and Risk Factors and Susceptibility to Laryngeal Cancer

    OpenAIRE

    Yu, Peng-Ju; Chen, Wei-Guan; Feng, Quan-Lin; Chen, Wei; Jiang, Man-Jie; Li, Ze-Qing

    2015-01-01

    Background The aim of this study was to investigate the association between polymorphism of the cytochrome P450 1B1 (CYP1B1) gene, a metabolic enzyme gene, and the susceptibility to laryngeal cancer among the Chinese Han population. Material/Methods In a case-control study, we investigated polymorphisms in the CYP1B1 gene (rs10012, rs1056827, and rs1056836) with a real-time quantitative polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 300 Chinese Han patients with ...

  15. Relationship between polymorphism of class Ⅱ transactivator gene promoters and chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Ying-Ren Zhao; Ling Gong; Ying-Li He; Fang Liu; Chang Lu

    2005-01-01

    AIM: To investigate the relationship between the polymorphism of class Ⅱ transactivator (CⅡTA) gene promoters and chronic hepatitis B (CHB).METHODS: Genomic DNA was prepared from peripheral blood leukocytes. Promoters Ⅰ, Ⅲ and Ⅳ of gene were analyzed respectively with polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) in 65 patients with CHB, 26 patients with acute hepatitis B (AHB) and 85 normal controls.RESULTS: No abnormal migration was found in PCR-SSCP analysis of the three promoters in the three groups. Also,no sequential difference was observed at the three promoters among the CHB patients, AHB patients and normal controls.CONCLUSION: No polymorphism in promoters Ⅰ, Ⅲ and Ⅳ of CⅡTA gene exists in CHB patients, ABH patients and normal controls, suggesting that the promoter of CⅡTA gene might be a conserved domain.

  16. Gene polymorphism of alpha-2 macroglobulin in patients with Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    HAO Yi-xin; FU Qiang; GUO Pin-e; ZHANG Jian-rong; SHEN Qian

    2005-01-01

    Objective: To explore the relationship between polymorphism of α2-macroglobulin (A2M)gene and Parkinson's disease (PD)in Han Nationality in Shanghai. Methods:The distributions of A2M gene polymorphism (a Val1000Ile in exon24, V/I)were detected in 66 PD patients and 120 healthy controls using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Results:The I allelic frequency in A2M exon24 gene of PD patients (90.9 %) was significantly lower than that of the healthy controls(96.3%)(OR=0.39,P=0. 033),so was the I/I genotype(OR=0.32,P=0. 015),especially in the patients more than 60 years old (OR= 0.31 ,P= 0.04). Conclusion :The I allele in exon24 of A2M gene might inhibit the onset of PD in Han Nationality in Shanghai.

  17. Promoter polymorphism of transforming growth factor-β1 gene and ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    B Tamizifar; KB Lankarani; S Naeimi; M Rismankar Zadeh; A Taghavi; A Ghaderi

    2008-01-01

    AIM: To elucidate the possible difference in two promoter polymorphisms of the transforming growth factor-β1 (TGF-β1) gene (-800G > A, -509C > T)between ulcerative colitis (UC) patients and normal subjects.METHODS: A total of 155 patients with established ulcerative colitis and 139 normal subjects were selected as controls. Two single nucleotide polymorphisms within the promoter region of TGF-β1 gene (-509C > T and -800G > A) were genotyped using PCR-RFLP.RESULTS: There was a statistically significant difference in genotype and allele frequency distributions between UC patients and controls for the -800G > A polymorphism of the TGF-β1 gene (P A of TGF-β1 gene promoter between Iranian patients with UC and normal subjects.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Polymorphisms in MTHFR, MS and CBS genes and premature acute myocardial infarction in a Pakistani population.

    Science.gov (United States)

    Iqbal, Mohammad Perwaiz; Iqbal, Khalida; Tareen, Asal Khan; Parveen, Siddiqa; Mehboobali, Naseema; Haider, Ghulam; Iqbal, Saleem Perwaiz

    2016-11-01

    High prevalence of premature coronary heart disease in Pakistanis compared to other populations points towards the genetic predisposition of this population to develop this disease. Since no investigations have been carried out in Pakistan to study the relationship of polymorphisms in genes involved in homocysteine cycle, the objective of the present study was to find out if there is any association of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; methionine synthase (MS) A2756G; cystathionine-β-synthase (CBS) 844ins68, G919A polymorphisms with premature acute myocardial infarction (AMI) in a population of Pakistani patients with this disease. In a cross-sectional study, DNA samples of 143 AMI patients (age CBS844ins68 polymorphisms and premature AMI in this population. This indicates that common polymorphisms in MTHFR, MS and CBS genes have no role in premature AMI in Pakistani population.

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

    Science.gov (United States)

    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.

  1. Apolipoprotein E gene polymorphism in cerebrovascular diseases of the Chinese Naxi populations from Yunnan province

    Institute of Scientific and Technical Information of China (English)

    Hong Xu; Qihong Yuan; Xijun Fan; Guoqiang He

    2011-01-01

    Currently it is not well known whether apolipoprotein E (ApoE) is a genetic susceptibility factor for cerebrovascular diseases in the Chinese Naxi population. The present study detected and sequenced ApoE polymorphisms of 90 patients with cerebrovascular diseases (58 cases of cerebral infarction and 32 cases of intracerebral hemorrhage), and 50 normal people of Naxi nationality from Yunnan province, China. The populations were used to analyze the relationship of ApoE polymorphisms with cerebral infarction and intracerebral hemorrhage. Results showed an association between ApoE gene polymorphism and the onset of cerebral infarction, and a possibility that the ε4 allele is a susceptibility locus for the risk of cerebral infarction. However, there was no evidence of a relationship between the ApoE gene polymorphism and cerebral hemorrhage.

  2. SIGNIFICANCE OF CYP3A5 GENE POLYMORPHISM IN SERBIAN RENAL TRANSPLANT PATIENTS

    Directory of Open Access Journals (Sweden)

    Nikola Stefanovi ć

    2013-03-01

    Full Text Available Tacrolimus (FK-506 is a part of most immunosuppressive protocols after kidney transplantation because it significantly affects the survival of transplanted organs in post - transplantation period. FK-506 is characterized by a narrow therapeutic index and large interindividual variability in pharmacokinetics. Partly, these variations can be explained by 6986A>G polymorphism CYP3A5 gene. As a substrate for CYP3A5 isoenzyme, FK–506 has a different elimination rate amnog individuals, which is caused by CYP3A5 gene polymorphism. The primary objective of this study was to investigate the frequency of CYP3A5 gene polymorphism (6986A>G in kidney transplant patients and comparison with the healthy volunteers. The second objective of this study was to determine the influence of the investigated polymorphism on FK–506 dosage regimen one month after kidney transplantation.Pharmacogenetic retrospective study included 121 examinees - 60 patients with renal transplant and 60 healthy volunteers. Patients have routine determination of drug concentration at the Clinic of Nephrology, Clinical Center Niš, Serbia. PCR method (Ashavaid TF et al. was used to determine the polymorphism of CYP3A5 gene. Our study did not show statistically significant differences in allele (p=0.616 and genotype (p=0.602 frequencies between the studied polymorphism in renal transplant patients and healthy volunteers. A statistically significant difference was found between patients with different genotypes of CYP3A5 regarding dose (p=0.001, weight adjusted dose (p=0.005, and dose normalized level of FK–506 (p=0.039 one month after transplantation. Patients with kidney transplant and healthy subjects in Serbian population did not show difference in the frequency of alleles of CYP3A5 gene. CYP3A5 gene polymorphism affects the dose regimen of tacrolimus one month after kidney transplantation. Acta Medica Medianae 2013;52(1:33-38.

  3. Two Polymorphisms in the Epithelial Cell-Derived Neutrophil-Activating Peptide (ENA-78 Gene

    Directory of Open Access Journals (Sweden)

    Mahsa M. Amoli

    2005-01-01

    Full Text Available Increased expression of epithelial cell-derived neutrophil-activating peptide (ENA-78 has been reported in several immune and inflammatory conditions suggesting its role in inflammatory response. We have identified two single nucleotide polymorphisms in the promoter and exon 2 of the ENA-78 gene by scanning the full length gene using DHPLC DNA fragment analysis and DNA sequencing.

  4. Association of metabolic gene polymorphisms with tobacco consumption in healthy controls.

    NARCIS (Netherlands)

    Smits, K.M.; Benhamou, S.; Garte, S.; Weijenberg, M.P.; Alamanos, Y.; Ambrosone, C.; Autrup, H.; Autrup, J.L.; Baranova, H.; Bathum, L.; Boffetta, P.; Bouchardy, C.; Brockmoller, J.; Butkiewicz, D.; Cascorbi, I.; Clapper, M.L.; Coutelle, C.; Daly, A.; Muzi, G.; Dolzan, V.; Duzhak, T.G.; Farker, K.; Golka, K.; Haugen, A.; Hein, D.W.; Hildesheim, A.; Hirvonen, A.; Hsieh, L.L.; Ingelman-Sundberg, M.; Kalina, I.; Kang, D.; Katoh, T.; Kihara, M.; Ono-Kihara, M.; Kim, H.L.; Kiyohara, C.; Kremers, P.; Lazarus, P.; Marchand, L. le; Lechner, M.C.; London, S.; Manni, J.J.; Maugard, C.M.; Morgan, G.J.; Morita, S.; Nazar-Stewart, V.; Kristensen, V.N.; Oda, Y.; Parl, F.F.; Peters, W.H.M.; Rannug, A.; Rebbeck, T.; Pinto, L.F.; Risch, A.; Romkes, M.; Salagovic, J.; Schoket, B.; Seidegard, J.; Shields, P.G.; Sim, E.; Sinnett, D.; Strange, R.C.; Stucker, I.; Sugimura, H.; To-Figueras, J.; Vineis, P.; Yu, M.C.; Zheng, W.; Pedotti, P.; Taioli, E.

    2004-01-01

    Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the associat

  5. Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas

    DEFF Research Database (Denmark)

    Berntsson, Shala Ghaderi; Wibom, Carl; Sjöström, Sara;

    2011-01-01

    The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade ...

  6. Drd4 gene polymorphisms are associated with personality variation in a passerine bird

    NARCIS (Netherlands)

    Fidler, A.E.; Van Oers, K.; Drent, P.J.; Kuhn, S.; Mueller, J.C.; Kempenaers, B.

    2007-01-01

    Polymorphisms in several neurotransmitter-associated genes have been associated with variation in human personality traits. Among the more promising of such associations is that between the human dopamine receptor D4 gene (Drd4) variants and novelty-seeking behaviour. However, genetic epistasis, gen

  7. Association analysis of the tyrosine hydroxylase gene polymorphisms with early-onset schizophrenia in Chinese population

    Institute of Scientific and Technical Information of China (English)

    吕钦谕

    2014-01-01

    Objective To investigate the relationship between the tyrosine hydroxylase(TH)gene and early-onset schizophrenia in Chinese Han population.Methods To tag single nucleotide polymorphisms(tag SNPs)rs2070762,rs6356 and rs11042978 in the TH gene were genotyped in 315 early-onset schizophrenics(188 male patients,127 female patients)and 391 controls subjects

  8. Polymorphism in genes for the enzyme arginine deiminase among Mycoplasma species.

    OpenAIRE

    Sugimura, K.; Ohno, T.; Azuma, I; Yamamoto, K.

    1993-01-01

    The extent of restriction fragment length polymorphism in genes for the arginine deiminase enzyme among 28 species of mycoplasmas was assessed by Southern blot analysis of DNA digested with EcoRI or TaqI nuclease probed with a 725-bp internal fragment of the arginine deiminase gene from Mycoplasma arginini. The results indicated unexpected heterogeneity among species of a single genus.

  9. Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes

    DEFF Research Database (Denmark)

    Vinther-Jensen, T; Nielsen, T T; Budtz-Jørgensen, E;

    2016-01-01

    -described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance...

  10. [Polymorphism of connexin 40 gene-- a novel genetic marker of the sick sinus node syndrome].

    Science.gov (United States)

    Chernova, A A; Nikulina, S Iu; Shul'man, V A; Kukushkina, T S; Voevoda, M I; Maksimov, V N

    2011-01-01

    In this work we have demonstrated for the first time on the clinico-genetic material association between hereditary sick sinus node syndrome and connexin 40 gene polymorphism. We have revealed that heterozygous variant of connexin 40 gene variant is more frequent among patients with sick sinus node syndrome and their healthy relatives than in persons of control group.

  11. Height in pre- and postmenopausal women is influenced by estrogen receptor alpha gene polymorphisms

    NARCIS (Netherlands)

    J.B.J. van Meurs (Joyce); A.P. Bergink (Arjan); M. van de Klift (Marjolein); Y. Fang (Yue); G. Leusink (Geraline); A.G. Uitterlinden (André); H.A.P. Pols (Huib); J.P.T.M. van Leeuwen (Hans); S.C.E. Schuit (Stephanie); A. Hofman (Albert)

    2004-01-01

    textabstractThe estrogen receptor alpha gene (ESR1) is known to be involved in metabolic pathways influencing growth. We have performed two population-based association studies using three common polymorphisms within this candidate gene to determine whether these are associated with variation in adu

  12. Drd4 gene polymorphisms are associated with personality variation in a passerine bird

    NARCIS (Netherlands)

    Fidler, A.E.; Van Oers, K.; Drent, P.J.; Kuhn, S.; Mueller, J.C.; Kempenaers, B.

    2007-01-01

    Polymorphisms in several neurotransmitter-associated genes have been associated with variation in human personality traits. Among the more promising of such associations is that between the human dopamine receptor D4 gene (Drd4) variants and novelty-seeking behaviour. However, genetic epistasis, gen

  13. Clinical response to antipsychotic drug treatment : Association study of polymorphisms in six candidate genes

    NARCIS (Netherlands)

    Vehof, Jelle; Burger, Huibert; Wilffert, Bob; Al Hadithy, Asmar; Alizadeh, Behrooz Z.; Snieder, Harold

    Pharmacogenetic studies have demonstrated significant associations between several candidate genes (DRD2, DRD3, 5HTR2A and 5HTR2C, COMT and MTHFR) and antipsychotic drug response. The present study investigates the effect of nine polymorphisms in these genes for an association with antipsychotic

  14. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China

    Institute of Scientific and Technical Information of China (English)

    Shao-shuai WANG; Fu-yuan QIAO; Ling FENG; Juan-juan LV

    2008-01-01

    Objective: To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), the central enzymes in folate metabolism that affects DNA methylation and synthesis, and the risk of Down syndrome in China. Methods: Genomic DNA was isolated from the peripheral lymphocytes of 64 mothers of children with Down syndrome and 70 age matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C→T, MTRR 66A→G and the relationship between these genotypes and the risk of Down syndrome was analyzed. Results: The results show that the MTHFR 677C→T polymorphism is more prevalent among mothers of children with Down syndrome than among control mothers, with an odds ratio of 3.78 (95% confidence interval (CI), 1.78~8.47). In addition, the homozygous MTRR 66A→G polymorphism was independently associated with a 5.2-fold increase in estimated risk (95% CI, 1.90~14.22). The combined presence of both polymorphisms was associated with a greater risk of Down syndrome than the presence of either alone, with an odds ratio of 6.0 (95% CI, 2.058~17.496).The two polymorphisms appear to act without a multiplicative interaction. Conclusion: MTHFR and MTRR gene mutation alleles are related to Down syndrome, and CT, TT and GG gene mutation types increase the risk of Down syndrome.

  15. HFE, MTHFR, and FGFR4 genes polymorphisms and breast cancer in Brazilian women.

    Science.gov (United States)

    Batschauer, Anna P; Cruz, Nathalia G; Oliveira, Vanessa C; Coelho, Fernanda F; Santos, Izabela R; Alves, Michelle T; Fernandes, Ana P; Carvalho, Maria G; Gomes, Karina B

    2011-11-01

    Genetic factors related to cancer have been extensively studied and several polymorphisms have been associated to breast cancer. The FGFR4, MTHFR, and HFE genes have been associated with neoplastic diseases development. The current report outlines the analysis of the polymorphisms G388A (FGFR4), C677T (MTHFR), C282Y, and H63D (HFE) in Brazilian breast cancer patients. We studied 68 patients with invasive ductal and operable breast carcinoma and 85 women as a control group. The polymorphism frequencies in the breast cancer and control groups were analyzed, but no significant difference was observed by comparing the two groups. The presence of each polymorphism was analyzed according to the clinical features and markers already established as prognostic in the breast cancer group. The C677T, H63D, and G388A polymorphisms were not associated to histological grade, age of diagnosis, expression of HER2 receptor, or estrogen and progesterone receptor. The H63D polymorphism showed a significant association (P = 0.02) with the presence of p53 mutations, and C667T showed association to lymph node involvement (P = 0.05). Lymph node involvement, G388A polymorphism, and histological grade were independently associated to metastasis/death. Our data suggests that the polymorphisms G388A, C677T, and H63D are not useful in breast cancer diagnosis, but they may be significant additional prognostic markers related to breast cancer survival.

  16. 5-Methyltetrahydrofolate-homocysteine methyltransferase gene polymorphism (MTR and risk of head and neck cancer

    Directory of Open Access Journals (Sweden)

    A.L.S. Galbiatti

    2010-05-01

    Full Text Available The functional effect of the A>G transition at position 2756 on the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase, involved in folate metabolism, may be a risk factor for head and neck squamous cell carcinoma (HNSCC. The frequency of MTR A2756G (rs1805087 polymorphism was compared between HNSCC patients and individuals without history of neoplasias. The association of this polymorphism with clinical histopathological parameters was evaluated. A total of 705 individuals were included in the study. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype the polymorphism. For statistical analysis, the chi-square test (univariate analysis was used for comparisons between groups and multiple logistic regression (multivariate analysis was used for interactions between the polymorphism and risk factors and clinical histopathological parameters. Using univariate analysis, the results did not show significant differences in allelic or genotypic distributions. Multivariable analysis showed that tobacco and alcohol consumption (P < 0.05, AG genotype (P = 0.019 and G allele (P = 0.028 may be predictors of the disease and a higher frequency of the G polymorphic allele was detected in men with HNSCC compared to male controls (P = 0.008. The analysis of polymorphism regarding clinical histopathological parameters did not show any association with the primary site, aggressiveness, lymph node involvement or extension of the tumor. In conclusion, our data provide evidence that supports an association between the polymorphism and the risk of HNSCC.

  17. Polymorphisms in the NPY and AGRP genes and body fatness in Dutch adults.

    OpenAIRE

    Rossum, Caroline T M van; Pijl, H.; Adan, R A H; Hoebee, Barbara; Seidell, J. C.

    2006-01-01

    OBJECTIVE: To investigate the association between DNA polymorphisms in the NPY and AGRP genes and body fatness. DESIGN AND METHODS: The association between the AGRP Ala67Thr or the NPY Leu7Pro polymorphisms and indicators of body fatness (baseline leptin levels, body mass index (BMI) values and prevalence of overweight) are investigated in 582 participants of two large cohorts in The Netherlands (total 18 500 adult men and women), aged 20-40 years whose weight remained relatively constant or ...

  18. P53 codon 11, 72, and 248 gene polymorphisms in endometriosis

    Directory of Open Access Journals (Sweden)

    Yao-Yuan Hsieh , Chich-Sheng Lin

    2006-01-01

    Full Text Available Objective: Mutated p53 gene is related to the instability of cell growth and cell cycle progression. We aimed to evaluate the association between endometriosis and p53 codon 11, 72 and 248 gene polymorphisms. Patients and methods: Women were divided into two groups: (1 moderate/severe endometriosis (n=148, and (2 non-endometriosis groups (n=150. P53 gene polymorphisms include codon11 Glu/Gln or Lys (GAG->CAG or AAG, codon 72 Arg/Pro (CGC->CCC, and codon 248 Arg/Thr (CGG->TCG. These gene polymorphisms were amplified by polymerase chain reaction and detected by electrophoresis after restriction enzyme (Taq I, BstU I, Hap II digestions. Associations between the endometriosis and p53 polymorphisms were evaluated. Results: The distributions of p53 codon 72 polymorphisms in both groups were significantly different. The proportions of Arg homozygotes/heterozygotes/Pro homozygotes in both groups were 9.5/66.2/24.3% and 30.7/50/19.3%. The proportions of Arg/Pro alleles were 42.6/57.4% and 56/44%. The distributions of p53 codon 11 and 248 polymorphisms in both groups were non-significantly different. All individuals appeared the wild genotypes (Glu11 and Arg248 homozygotes. Conclusion: Association between endometriosis and p53 codon 72 polymorphism exists. P53 codon 72*Pro-related genotype and allele are related with higher susceptibility of endometriosis. P53 codon 11 and 248 polymorphisms are not related with endometriosis susceptibility.

  19. Distress of ostracism: oxytocin receptor gene polymorphism confers sensitivity to social exclusion

    OpenAIRE

    McQuaid, Robyn J.; McInnis, Opal A.; Matheson, Kimberly; Anisman, Hymie

    2015-01-01

    A single-nucleotide polymorphism on the oxytocin receptor gene (OXTR), rs53576, involving a guanine (G) to adenine (A) substitution has been associated with altered prosocial features. Specifically, individuals with the GG genotype (i.e. the absence of the polymorphism) display beneficial traits including enhanced trust, empathy and self-esteem. However, because G carriers might also be more socially sensitive, this may render them more vulnerable to the adverse effects of a negative social s...

  20. Associations of the decoy receptor and osteoprotegerin gene polymorphisms with ulcerative colitis in Chinese patients

    Institute of Scientific and Technical Information of China (English)

    郑香云

    2014-01-01

    Objective To investigate the correlation between decoy receptor(DcR)1,DcR2 and osteoprotegerin(OPG)gene polymorphisms with the susceptibility to ulcerative colitis(UC)in Chinese population.Methods A total of352 patients with UC as well as 463 sex-and agematched healthy controls were recruited in the study.The genetic polymorphisms of DcR1(rs12549481),DcR2(rs1133782)and OPG(rs3102735)were deter-

  1. Cytokine gene polymorphisms and their association with cervical cancer: A North Indian study

    OpenAIRE

    2016-01-01

    Introduction: The production of cytokines, growth factors and adhesion molecules promotes tumor progression and involves inflammation, angiogenesis and thrombosis, thus providing optimal conditions for cancer development. 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-1β-511C/T (rs16944) and ...

  2. Combined folate gene MTHFD and TC polymorphisms as maternal risk factors for Down syndrome in China.

    Science.gov (United States)

    Liao, Y P; Zhang, D; Zhou, W; Meng, F M; Bao, M S; Xiang, P; Liu, C Q

    2014-03-17

    We examined whether polymorphisms in the methylenetetrahydrofolate dehydrogenase (MTHFD) and transcobalamin (TC) genes, which are involved in folate metabolism, affect maternal risk for Down syndrome. We investigated 76 Down syndrome mothers and 115 control mothers from Bengbu, China. Genomic DNA was isolated from the peripheral lymphocytes. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFD G1958A and TC C776G. The frequencies of the polymorphic alleles were 24.3 and 19.1% for MTHFD 1958A, 53.9 and 54.2% for TC 776G, in the case and control groups, respectively. No significant differences were found between two groups in relation to either the allele or the genotype frequency for both polymorphisms. However, when gene-gene interactions between these two polymorphisms together with previous studied C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were analyzed, the combined MTHFR 677CT/TT and MTHFD 1958AA/GA genotype was found to be significantly associated with the risk of having a Down syndrome child [odds ratio (OR) = 3.11; 95% confidence interval (95%CI) = 1.07-9.02]. In addition, the combined TC 776CG and MTHFR 677TT genotype increased the risk of having a child with Down syndrome 3.64-fold (OR = 3.64; 95%CI = 1.28-10.31). In conclusion, neither MTHFD G1958A nor TC C776G polymorphisms are an independent risk factor for Down syndrome. However, the combined MTHFD/MTHFR, TC/MTHFR genotypes play a role in the risk of bearing a Down syndrome child in the Chinese population.

  3. Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population.

    Science.gov (United States)

    Kallel, Amani; Sbaï, Mohamed Hédi; Sediri, Yousra; Abdessalem, Salem; Mourali, Mohamed Sami; Feki, Moncef; Mechmeche, Rachid; Jemaa, Riadh; Kaabachi, Naziha

    2013-12-01

    Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the -786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects. A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and -786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR. There was significant linkage disequilibrium between the three NOS3 polymorphisms (pNOS3 4a4b, but not -786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24-15.41; p=0.021, dominant model OR: 1.66, 95%CI: 1.14-2.42); p=0.007, and recessive model OR: 3.85, 95%CI: 1.10-13.47; p=0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR=12.05, p=0.010) was a risk factor of MI after controlling for classical risk factors. These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. The impact of a TSH receptor gene polymorphism on thyroid-related phenotypes in a healthy Danish twin population

    DEFF Research Database (Denmark)

    Hansen, P.S.; Deure, W.M. van der; Peeters, R.P.;

    2007-01-01

    OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size...

  5. Inter-ethnic polymorphism of the beta-globin gene locus control region (LCR) in sickle-cell anemia patients.

    Science.gov (United States)

    Périchon, B; Ragusa, A; Lapouméroulie, C; Romand, A; Moi, P; Ikuta, T; Labie, D; Elion, J; Krishnamoorthy, R

    1993-06-01

    Sequence polymorphisms within the 5'HS2 segment of human locus control region is described among sickle cell anemia patients. Distinct polymorphic patterns of a simple sequence repeat are observed in strong linkage disequilibrium with each of the five major beta s haplotypes. Potential functional relevance of this polymorphic region in globin gene expression is discussed.

  6. Expression of IL-4 receptor on human T and B lymphocytes.

    Science.gov (United States)

    Zola, H; Flego, L; Weedon, H

    1993-08-01

    The expression of the interleukin-4 receptor on human blood and tonsil lymphocytes has been studied using a monoclonal antibody and high-sensitivity immunofluorescence flow cytometry. While no receptor expression could be detected on circulating or tonsil T cells, a subset of B cells was shown to express the receptor. The IL-4R-positive B cells in tonsil had a phenotype suggesting that they included both germinal centre B cells and B cells outside the germinal centre. The subset of B cells in the blood that expressed the receptor included CD23-positive B cells. Activation of tonsil B cells using anti-IgM, IL-4, IL-2, or combinations of these reagents led to increases in IL-4R expression, but these changes were small compared to changes in the expression of IL-2R p55 (CD25), a known marker of activation. Similarly, activation of T cells led to low-level expression of IL-4R, with IL-4 itself up-regulating IL-4R, especially in CD4 cells. The majority of chronic lymphocytic leukaemia samples were positive for IL-4R expression, whilst most other leukemic samples were negative.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wilding, Craig S. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom)]. E-mail: craig.wilding@westlakes.ac.uk; Relton, Caroline L. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom); Paediatric and Lifecourse Epidemiology Research Group, School of Clinical Medical Sciences (Child Health), Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle-upon-Tyne NE1 4LP (United Kingdom); Rees, Gwen S. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom); Tarone, Robert E. [International Epidemiology Institute, 1455 Research Boulevard, Suite 550, Rockville, MD 20850 (United States); Whitehouse, Caroline A. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom); Tawn, E. Janet [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom)

    2005-02-15

    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]{sub n} microsatellite in the 3' UTR) and double strand break repair (XRCC3 T241M and a [AC]{sub 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.

  8. 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.

  9. Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster

    Energy Technology Data Exchange (ETDEWEB)

    Vora, D.K.; Rosenbloom, C.L.; Cottingham, R.W. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-06-01

    Genetic polymorphisms in leukocyte and endothelial cell adhesion molecules may be important variables with regard to susceptibility to multifactorial disease processes that include an inflammatory component. For this reason, polymorphisms were sought for intercellular adhesion molecule-1 (ICAM-1; gene symbol ICAM1) and for the three genes in the selectin cluster, P-selectin, L-selectin, and E-selectin (gene symbols SELP, SELL, and SELE, respectively). Two amino acid polymorphisms were identified for ICAM-1; Gly or Arg at codon 241 and Lys or Glu at codon 469. Dinucleotide repeat polymorphisms were identified in the 3{prime}-untranslated region for ICAM-1 and in intron 9 for P-selectin. Restriction fragment length polymorphisms were found using cDNAs for each of the three selectin genes as probes; E-selectin with BglII, P-selectin with ScaI, and L-selectin with HincII. Linkage analysis was performed for the selectin gene cluster and for ICAM-1 using the CEPH families; ICAM-1 is very tightly linked to the LDL receptor on chromosome 19, and the selectin cluster is linked to markers at chromosome 1q23. 41 refs., 2 tabs.

  10. Is catechol-o-methyltransferase gene polymorphism a risk factor in the development of premenstrual syndrome?

    Science.gov (United States)

    Deveci, Esma Ozturk; Selek, Salih; Camuzcuoglu, Aysun; Hilali, Nese Gul; Camuzcuoglu, Hakan; Erdal, Mehmet Emin; Vural, Mehmet

    2014-01-01

    Objective The objective of this study was to investigate whether there was a correlation between catechol-o-methyltransferase (COMT) gene polymorphism, which is believed to play a role in the etiology of psychotic disorders, and premenstrual syndrome (PMS). Methods Fifty-three women with regular menstrual cycles, aged between 18 and 46 years and diagnosed with PMS according to the American Congress of Obstetrics and Gynecology criteria were included in this study as the study group, and 53 healthy women having no health problems were selected as the controls. Venous blood was collected from all patients included in the study and kept at -18℃ prior to analysis. Results There was no significant difference between the groups in terms of demographic features such as age, body mass index, number of pregnancies, parity, and number of children. No statistically significant difference was observed in terms of COMT gene polymorphism (p=0.61) between women in the PMS and the control groups. However, a significant difference was found between arthralgia, which is an indicator of PMS, and low-enzyme activity COMT gene (Met/Met) polymorphism (p=0.04). Conclusion These results suggested that there was no significant relationship between PMS and COMT gene polymorphism. Since we could not find a direct correlation between the COMT gene polymorphism and PMS, further studies including alternative neurotransmitter pathways are needed to find an effective treatment for this disease. PMID:25045629

  11. Angiotensin II type 1 receptor (A1166C gene polymorphism and essential hypertension in Egyptian population

    Directory of Open Access Journals (Sweden)

    Marium M. Shamaa

    2016-09-01

    Full Text Available The pathogenesis of essential hypertension (EH is affected by genetic and environmental factors. Mutations in hypertension-related genes can affect blood pressure (BP via alteration of salt and water reabsorption by the nephron. The genes of the renin-angiotensin system (RAS have been extensively studied because of the well documented role of this system in the control of BP. It has been previously shown that Angiotensin II type 1 receptor (ATR1 gene polymorphism could be associated with increased risk of EH. So, in the current study, we evaluated the frequency of ATR1 (A1166C polymorphism in relation to EH in a group of Egyptian population. The study population included 83 hypertensive patients and 60 age and sex matched healthy control subjects. Restriction fragment length polymorphism – Polymerase chain reaction (RFLP – PCR was used for the analysis of A1166C polymorphism of ATR1 genes in peripheral blood samples of all patients and controls. The results revealed that there was a positive risk of developing EH when having the T allele whether in homozygous or heterozygous state. From this work, it was concluded that there was an association between ATR1 (A1166C gene polymorphism and the risk of developing EH.

  12. Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis.

    Science.gov (United States)

    Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof; Pawlik, Andrzej

    2017-08-01

    Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04-2.28; p = 0.035). The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity.

  13. Association between CYP1A1m1 gene polymorphism and primary open-angle glaucoma.

    Science.gov (United States)

    Costa, N B; Silva, C T X; Frare, A B; Silva, R E; Moura, K K V O

    2014-12-04

    The CYP1A1 gene is related to the generation of secondary metabolites that are capable of inducing DNA damage. The CYP1A1m1 polymorphism has been examined in many studies, and is located in a region near loci that have been linked to glaucoma, including the locus GLC1I. As a result, this polymorphism has been related to several diseases that are influenced by exposure to xenobiotic as well as primary open-angle glaucoma. We compared the prevalence of the CYP1A1m1 polymorphism in 152 Brazilian patients, 100 patients with primary open-angle glaucoma, and 52 normal controls using restriction fragment length polymorphism analysis. The frequency of the homozygous wild-type (w1/w1) CYP1A1 gene among patients with primary open-angle glaucoma (N = 100) was 16%, for genotype w1/m1, the frequency was 77%, and for m1/m1 it was 7%. Among the control group (N = 52), the frequency of the homozygous wild-type (w1/w1) CYP1A1 gene was 54%, the frequency of w1/m1 was 46%, and the frequency of m1/m1 was 0%. The presence of the CYP1A1m1 polymorphism may interfere with xenobiotic metabolism and exacerbate direct or indirect damage to the optic nerve. These CYP1A1m1 polymorphisms may be risk factors for primary open-angle glaucoma.

  14. Investigation on estrogen receptor alpha gene polymorphisms in Iranian women with recurrent pregnancy loss

    Science.gov (United States)

    Mahdavipour, Marzieh; Idali, Farah; Zarei, Saeed; Talebi, Saeed; Fatemi, Ramina; Jeddi-Tehrani, Mahmood; Pahlavan, Somayeh; Rajaei, Farzad

    2014-01-01

    Background: Recurrent pregnancy loss (RPL) is a multifactorial disorder. Environmental factors and genetics can affect pregnancy outcomes. Objective: Conflicting data suggest an association between estrogen receptor alpha (ESR1) gene polymorphisms and RPL. In this study, such association was investigated in Iranian women with RPL. Materials and Methods: In this case control study, blood samples were collected from 244 women with a history of three or more consecutive pregnancy losses and 104 healthy women with at least two live births. Using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), we studied -397C/T and -351A/G polymorphisms on ESR1 gene in case and control subjects. Results: The genotypic frequencies of -397C/T and -351A/G polymorphisms on ESR1were not significantly different between RPL and control groups (p=0.20 and p=0.09, respectively). A significantly negative correlation was observed between -397C/T and -351A/G (r=-0.852, p<0.001) in RPL women and complete linkage disequilibrium between the investigated polymorphisms was found (D’: 0.959; r-square= 0.758, p<0.001). Conclusion: This investigation suggests that the analyzed polymorphisms on ESR1gene are not associated with an increased risk of RPL in the studied population. PMID:25071847

  15. NO ASSOCIATION BETWEEN tHbmass AND POLYMORPHISMS IN THE HBB GENE IN ENDURANCE ATHLETES.

    Science.gov (United States)

    Malczewska-Lenczowska, J; Orysiak, J; Majorczyk, E; Pokrywka, A; Kaczmarski, J; Szygula, Z; Sitkowski, D

    2014-06-01

    The aim of this study was to examine the association between tHbmass and HBB gene polymorphisms in athletes of endurance disciplines. Eighty-two well-trained athletes (female n=36, male n=46), aged 19.3 ± 2.7 years, representing cross country skiing (n=37) and middle- and long-distance running (n=45), participated in the study. Genotyping for 2 polymorphisms in the HBB gene (- 551C/T and intron 2, +16 C/G) was performed using restriction fragment length polymorphism analysis. Total haemoglobin mass (tHbmass) was determined by the optimized carbon monoxide rebreathing method. Blood morphology, indices of iron status (ferritin, transferrin receptor and total iron binding capacity) and C reactive protein were also determined. No differences were found in the HBB genotype and allele frequencies between male and female athletes. Regardless of the polymorphisms, no relationships were found between HBB genotypes as well as alleles and relative values of tHbmass, expressed per body mass (g · kg(-1) BM), both in female and male athletes. Our results demonstrated that -551 C/T and intron 2, +16 C/G polymorphisms of the HBB gene have no association with total haemoglobin mass in endurance athletes. It cannot be ruled out that several polymorphisms, each with a small but significant contribution, may be responsible for the amount of haemoglobin.

  16. ASSOCIATION ANALYSIS OF POLYMORPHISMS OF ACE GENE AND AGT GENE WITH ESSENTIAL HYPERTENSION IN CHINESE HAN'S POPULATION

    Institute of Scientific and Technical Information of China (English)

    刘英; 周文郁; 侯淑琴; 邱长春

    1998-01-01

    Objective. To investigate whether the polymorphisms in the angiotensin converting enxyme (ACE) gene and angiotensinogen (AGT) gene are associated with essential hypertension. Methods. A case-contrul study was carried out using 103 hypertensive (HT) and 131 normotensive (NT) subjects. The insertion/daletion(I/D) polymorphism of the ACE gene and the methionine→threonine variant at position 235 (M235T) of the AGT gene were determined by the polymerase chain reaction (PCR) technique and PCR/restriction fragment length polymorphism (PCR/RFLP) analysis, respectively. Results. The differences of D allele frequency and genotype distribution of the ACE gene between NT and HT groups were statistically significant (X2= 18.12,P<0. 005). The T235 allele frequeacy of the AGT gene was 69% in NT Chinese group (approximately 1.38 to 1.64 fold that in Caucasians), and was greater in female HT than in NT (0.82 vs 0. 72, X2=8. 1,P<0.025). A corralation between M235T molecular variant of the AGT gene and I/D molecular variant of ACE gene to hypertension was found. Concluions. The possession of D allele of the ACE gene might be a marker for predisposition to hypertension. The T235 allele of the AGT gene was more common in Chinese than in Caucasians, and might contribute to the risk for hypertension in female Chinese.

  17. Gene-gene interaction and functional impact of polymorphisms on innate immune genes in controlling Plasmodium falciparum blood infection level.

    Directory of Open Access Journals (Sweden)

    Madhumita Basu

    Full Text Available Genetic variations in toll-like receptors and cytokine genes of the innate immune pathways have been implicated in controlling parasite growth and the pathogenesis of Plasmodium falciparum mediated malaria. We previously published genetic association of TLR4 non-synonymous and TNF-α promoter polymorphisms with P.falciparum blood infection level and here we extend the study considerably by (i investigating genetic dependence of parasite-load on interleukin-12B polymorphisms, (ii reconstructing gene-gene interactions among candidate TLRs and cytokine loci, (iii exploring genetic and functional impact of epistatic models and (iv providing mechanistic insights into functionality of disease-associated regulatory polymorphisms. Our data revealed that carriage of AA (P = 0.0001 and AC (P = 0.01 genotypes of IL12B 3'UTR polymorphism was associated with a significant increase of mean log-parasitemia relative to rare homozygous genotype CC. Presence of IL12B+1188 polymorphism in five of six multifactor models reinforced its strong genetic impact on malaria phenotype. Elevation of genetic risk in two-component models compared to the corresponding single locus and reduction of IL12B (2.2 fold and lymphotoxin-α (1.7 fold expressions in patients'peripheral-blood-mononuclear-cells under TLR4Thr399Ile risk genotype background substantiated the role of Multifactor Dimensionality Reduction derived models. Marked reduction of promoter activity of TNF-α risk haplotype (C-C-G-G compared to wild-type haplotype (T-C-G-G with (84% and without (78% LPS stimulation and the loss of binding of transcription factors detected in-silico supported a causal role of TNF-1031. Significantly lower expression of IL12B+1188 AA (5 fold and AC (9 fold genotypes compared to CC and under-representation (P = 0.0048 of allele A in transcripts of patients' PBMCs suggested an Allele-Expression-Imbalance. Allele (A+1188C dependent differential stability (2 fold of IL12B-transcripts upon

  18. Functional characterization of genetic polymorphisms identified in the promoter region of the bovine PEPS gene.

    Science.gov (United States)

    Ju, Zhihua; Zheng, Xue; Huang, Jinming; Qi, Chao; Zhang, Yan; Li, Jianbin; Zhong, Jifeng; Wang, Changfa

    2012-06-01

    Peptidase S (PEPS) is a metallopeptidase that cleaves N-terminal residues from proteins and peptides. PEPS is used as a cell maintenance enzyme with critical roles in peptide turnover. The promoter region located upstream of the initiation site plays an important role in regulating gene expression. Polymorphism in the promoter region can alter gene expression and lead to biological changes. In the current study, polymorphisms in the promoter region of the PEPS gene were investigated. Polymerase chain reaction (PCR)-restriction fragment length polymorphism and DNA sequencing methods were used to screen sequence variations in the promoter region of DNA samples from 743 Chinese Holstein cattle. Two polymorphisms (g. -534 T>C and g. -2545 G>A) were identified and eight haplotypes were classified by haplotype analysis. The two genetic polymorphisms and haplotypes were associated with fat percentage and somatic cell score in Chinese Holstein cattle. The results of real-time PCR showed that cow kidneys exhibit the highest PEPS expression level. Moreover, bioinformatics analysis predicted that the single-nucleotide polymorphism g. -534 T>C is located in the core promoter region and in the transcription factor binding sites. The promoter activities of the polymorphism of -543 T>C were measured by luciferase assay in the human kidney epithelial cell line 293T. Transcriptional activity is significantly lower in cell lines transfected with the reporter construct containing 2.5 kb upstream fragments with -543 C than in those with wild-type -543 T. The results indicated that genetic variation at locus -543 influences PEPS promoter activity. The genetic variation in the promoter region of PEPS gene may regulate PEPS gene transcription and might have consequences at a regulatory level.

  19. Angiotensinogen gene polymorphisms in IDDM patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Tarnow, L; Cambien, Francois; Rossing, P

    1996-01-01

    /TM/MM genotypes, respectively. In patients with nephropathy, systolic blood pressure was higher (161 +/- 22 mmHg [mean +/- SD]) in patients carrying TT genotype of the M235T angiotensinogen polymorphism as compared with patients with MM or MT genotypes (150 +/- 23 mmHg; P = 0.03). We conclude that neither the M...

  20. 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

    2017-01-01

    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.

  1. Associations between the IL-4 -590 T allele and Plasmodium falciparum infection prevalence in asymptomatic Fulani of Mali.

    Science.gov (United States)

    Vafa, Manijeh; Maiga, Bakary; Berzins, Klavs; Hayano, Masashi; Bereczky, Sandor; Dolo, Amagana; Daou, Modibo; Arama, Charles; Kouriba, Bourema; Färnert, Anna; Doumbo, Ogobara K; Troye-Blomberg, Marita

    2007-07-01

    In this study, we compared the genotype and allele frequencies of the IL-10 -1087 A/G and IL-4 -590 C/T single nucleotide polymorphisms in asymptomatic subjects of two sympatric ethnic tribes differing in susceptibility to malaria, the Fulani and the Dogon in Mali. The genotype data was correlated with ethnicity and malariometric indexes. A statistically significant inter-ethnic difference in allele and genotype frequency for both loci was noted (PDogon. Inter-ethnic differences in spleen rates, higher in the Fulani than the Dogon, were seen between T carriers (TT and CT) of both groups (PDogon. No associations between IL-10 genotypes and studied malariometric indexes were observed in any of the two communities.

  2. Gene-Gene Interactions Among PRKCA, NOS3 and BDKRB2 Polymorphisms Affect the Antihypertensive Effects of Enalapril.

    Science.gov (United States)

    Oliveira-Paula, Gustavo H; Luizon, Marcelo R; Lacchini, Riccardo; Fontana, Vanessa; Silva, Pamela S; Biagi, Celso; Tanus-Santos, Jose E

    2017-03-01

    Protein kinase C (PKC) signalling is critically involved in the control of blood pressure. Angiotensin-converting enzyme inhibitors (ACEi) affect PKC expression and activity, which are partially associated with the responses to ACEi. We examined whether PRKCA (protein kinase C, alpha) polymorphisms (rs887797 C>T, rs1010544 T>C and rs16960228 G>A), or haplotypes, and gene-gene interactions within the ACEi pathway affect the antihypertensive responses in 104 hypertensive patients treated with enalapril as monotherapy. Patients were classified as poor responders (PR) or good responders (GR) to enalapril if their changes in mean arterial pressure were lower or higher than the median value, respectively. Multi-factor dimensionality reduction was used to characterize interactions among PRKCA, NOS3 (nitric oxide synthase 3) and BDKRB2 (bradykinin receptor B2) polymorphisms. The TC+CC genotypes for the rs1010544 polymorphism were more frequent in GR than in PR (p = 0.037). Conversely, the GA+AA genotypes for the rs16960228 polymorphism, and the CTA haplotype, were more frequent in PR than in GR (p = 0.040 and p = 0.008, respectively). Moreover, the GG genotype for the PRKCA rs16960228 polymorphism was associated with PR or GR depending on the genotypes for the rs2070744 (NOS3) and rs1799722 (BDKRB2) polymorphisms (p = 0.012). Our results suggest that PRKCA polymorphisms and gene-gene interactions within the ACEi pathway affect the antihypertensive responses to enalapril. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  3. The influence of Angiotensin converting enzyme and angiotensinogen gene polymorphisms on hypertrophic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Rong Luo

    Full Text Available Some studies have reported that angiotensin converting enzyme (ACE and angiotensinogen (AGT genes have been associated with hypertrophic cardiomyopathy (HCM. However, there have been inconsonant results among different studies. To clarify the influence of ACE and AGT on HCM, a systemic review and meta-analysis of case-control studies were performed. The following databases were searched to indentify related studies: PubMed database, the Embase database, the Cochrane Central Register of Controlled Trials database, China National Knowledge Information database, and Chinese Scientific and Technological Journal database. Search terms included "hypertrophic cardiomyopathy", "angiotensin converting enzyme" (ACE or "ACE" and "polymorphism or mutation". For the association of AGT M235T polymorphism and HCM, "angiotensin converting enzyme" or "ACE" was replaced with "angiotensinogen". A total of seventeen studies were included in our review. For the association of ACE I/D polymorphism and HCM, eleven literatures were included in the meta-analysis on association of penetrance and genotype. Similarly, six case-control studies were included in the meta-analysis for AGT M235T. For ACE I/D polymorphism, the comparison of DI/II genotype vs DD genotype was performed in the present meta-analysis. The OR was 0.73 (95% CI: 0.527, 0.998, P = 0.049, power = 94%, alpha = 0.05 after the study which deviated from Hardy-Weinberg Equilibrium was excluded, indicating that the ACE I/D gene polymorphism might be associated with HCM. The AGT M235T polymorphism did not significantly affect the risk of HCM. In addition, ACE I/D gene polymorphism did not significantly influence the interventricular septal thickness in HCM patients. In conclusion, the ACE I/D polymorphism might be associated with the risk of HCM.

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

    Directory of Open Access Journals (Sweden)

    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

  5. Polymorphism and signatures of selection in the multimammate rat DQB gene

    DEFF Research Database (Denmark)

    de Bellocq, Joëlle Goüy; Leirs, Herwig

    2010-01-01

    for exon 2 of DQB using capillary electrophoresis single-strand conformation polymorphism, cloning, and sequencing. We found 21 different alleles. Four individuals show three alleles implying a duplication event in the history of this gene. Each distinct sequence translates to give a distinct amino acid......In order to test if DQB is a good candidate marker to investigate the relationship between major histocompatibility complex genes and pathogens in natural populations of Mastomys natalensis, we assessed the polymorphism and evolutionary history of this gene. Twenty-four individuals were genotyped...... sequence and there are strong signals of positive selection on peptide binding sites. Signals of recombination were found in the sequences suggesting that recombination has played a role in generating allelic diversity. Although trans-taxon polymorphism is present at the interspecific level in DQB exon 2...

  6. An association study between polymorphisms in five genes in glutamate and GABA pathway and paranoid schizophrenia.

    Science.gov (United States)

    Zhang, Boyu; Yuan, Yanbo; Jia, Yanbin; Yu, Xin; Xu, Qi; Shen, Yucun; Shen, Yan

    2005-01-01

    Dysfunctions of glutamatergic and GABAergic neurotransmission are two important hypotheses for the pathogenesis of schizophrenia. Thus, genes in the pathway are candidates for schizophrenia susceptibility. Phosphate-activated glutaminase (GLS), glutamine synthetase (GLUL), glutamic acid decarboxylase (GAD), GABA transaminase (ABAT) and succinic semialdehyde dehydrogenase (ALDH5A1) are five primary enzymes in glutamate and GABA synthetic and degradative pathway. In order to investigate the possible involvement of these genes in the development of paranoid schizophrenia, we genotyped 80 paranoid schizophrenics from northern China and 108 matched controls by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) methods or directly sequencing of PCR product. Seven SNPs were found to be polymorphic in the population investigated. No significant differences in the genotype distributions or allele frequencies between patients and controls were found. Therefore, we conclude the polymorphisms studied in the five genes do not play major roles in pathogenesis of paranoid schizophrenia in the population investigated.

  7. Association of Interleukin-10 Gene Promoter Polymorphisms in Saudi Patients with Vitiligo

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    Abdullah Abanmi

    2008-01-01

    Full Text Available The promoter region of human Interleukin −10 gene is highly polymorphic and has been associated with numerous autoimmune diseases. Recent studies have linked vitiligo with defective autoimmune system. This study is aimed to explore a possible association between IL-10 gene polymorphism and vitiligo in Saudi population. This case control study consisted of 184 Saudi subjects including 83 vitiligo patients (40 males, 43 females mean age 27.85 ± 12.43 years and 101 matched controls. Genomic DNA was extracted from the blood samples of healthy controls and Vitiligo patients visiting out patient clinic of Department of Dermatology, Riyadh Armed Forces Hospital, using QIA ampR DNA mini kit (Qiagen CA, USA. Interleukin-10 gene was amplified by polymerase chain reaction (PCR using Arms primers to detect any polymorphism involved at positions −592, −819 and −1082.

  8. Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

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    Hahner Stefanie

    2008-07-01

    Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

  9. EVC gene polymorphisms and risks of isolated hypospadias – a preliminary study

    Science.gov (United States)

    Kowal, Andrzej; Mostowska, Adrianna; Mydlak, Dariusz; Eberdt-Gołąbek, Bożena; Misztal, Matthew; Jagodziński, Paweł P.

    2015-01-01

    Introduction Hypospadias has a complex etiology with both genetic and environmental factors contributing to the condition. Urogenital abnormalities including hypospadias, are found in 22% of cases with Ellis van Creveld syndrome (EvC). Mutations in the EVC gene can cause major and minor anomalies, which form phenotypes that partially overlap with those present in EvC. The aim of this study was to evaluate the association between nucleotide variants of the EVC gene and the risk of hypospadias. Material and methods Four single nucleotide polymorphisms (SNPs) of the EVC gene (rs3774856, rs2302075, rs1383180, rs7680768) were taken under investigation in 96 patients with isolated hypospadias and 284 matched controls. Genotyping of all polymorphisms was carried out by PCR and followed by appropriate restriction enzyme digestion (PCR-RFLP). Results Individuals homozygous for the SNP rs2302075 (p.Thr449Lys) showed an elevated risk for hypospadias. Haplotypes containing the rs2302075 variant also revealed modest associations with hypospadias, which did not survive multiple testing corrections. None of the other tested EVC polymorphisms displayed significant association with the risk of hypospadias, either in dominant or recessive inheritance models. Conclusions The results of this study suggest that polymorphic variants of the EVC gene do not substantially contribute to the risk of hypospadias based on our study population. However, further studies should help to clarify the relationship between polymorphisms of EVC and hypospadias. PMID:26251756

  10. Relationship between plasminogen activator inhibitor type-1 (PAI-1 gene polymorphisms and osteoporosis in Turkish women

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    Merih Ozgen

    2012-11-01

    Full Text Available OBJECTIVE: The development of osteoporosis is associated with several risk factors, such as genetic structures that affect bone turnover and bone mass. The impact of genetic structures on osteoporosis is not known. Plasminogen activator inhibitor type-1 regulates the bone matrix and bone balance. This study assessed the correlation between plasminogen activator inhibitor type-1 gene 4G/5G polymorphisms and osteoporosis in a population of Turkish women. METHODS: A total of 195 postmenopausal female patients who were diagnosed with osteoporosis (Group I based on bone mineral density measurements via dual-energy x-ray absorptiometry and 90 females with no osteoporosis (Group II were included in this study. Correlations between PAI-1 gene 4G/5G polymorphisms and osteoporosis were investigated through the identification of PAI-1 gene 4G/5G polymorphism genotypes using the polymerase chain reaction. RESULTS: No significant differences in the genotype and allele frequency of 4G/5G plasminogen activator inhibitor type-1 polymorphisms were observed between the two groups, and both groups exhibited the most frequently observed 4G5G genotype. CONCLUSION: No correlation between the development of osteoporosis in the female Turkish population and 4G/5G plasminogen activator inhibitor type-1 gene polymorphisms was observed.

  11. Association of interleukin-10 gene polymorphisms with breast cancer in a Chinese population

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    Song Bao

    2010-06-01

    Full Text Available Abstract Backgroud Interleukin-10(IL-10 is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine interindividual differences in IL-10 production. This study was performed to determined whether polymorphisms in the IL-10 gene promoter were associated with breast cancer in a Chinese Han population. Methods We genotyped 315 patients with breast cancer and 322 healthy control subjects for -1082A/G, -819T/C and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP. Results There were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Analysis of breast cancer prognostic and predictive factors revealed that the -1082AA genotype was associated with a significantly increased risk of lymph node (LN involvement (P = 0.041 and larger tumor size (P = 0.039 at the time of diagnosis. Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher LN involvement (p = 0.022 and higher tumor stage(p = 0.028 of breast cancer at the time of diagnosis compared with others. Conclusions Our findings suggest that IL-10 promoter polymorphisms participate in the progression of breast cancer rather than in its initial development in Chinese Han women.

  12. Pro12Ala PPAR gamma2 gene polymorphism in women with polycystic ovary syndrome.

    Science.gov (United States)

    Bidzińska-Speichert, Bozena; Lenarcik, Agnieszka; Tworowska-Bardzińska, Urszula; Slezak, Ryszard; Bednarek-Tupikowska, Grazyna; Milewicz, Andrzej; Krepuła, Katarzyna

    2011-06-01

    The pathogenesis of PCOS has not been definitively determined and includes a number of genes linked with steroidogenesis, regulation of gonadotropin secretion, actions of insulin, obesity as well as chronic inflammatory processes. Some authors indicate that PPARgamma play a role in insulin sensitivity and are probably involved in hyperandrogenism in PCOS. The aim of the study was to assess the frequency of the Pro12Ala and Pro115Gln PPARgamma2 gene polymorphisms in women with PCOS. 54 PCOS women and 51 healthy women were recruited. Genetic studies to detect Pro12Ala and Pro115Gln PPARgamma2 gene polymorphism were performed. In the whole studied group the Pro115Gln polymorphism of the PPARgamma2 gene was not found. The frequency of the Pro12Ala polymorphism was estimated at 26.47% in the controls and at 23.15% in the PCOS patients. Women from the control and PCOS groups with BMI > or = 30 had statistically higher occurrence of the Ala allele than women with BMI Pro12Ala polymorphism observed in the sample of women from the Lower Silesian population was significantly higher than in the majority of European populations.

  13. 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.

  14. IL-4 induces cAMP and cGMP in human monocytic cells

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    B. Dugas

    1995-01-01

    Full Text Available Human monocytes, preincubated with IFN-γ respond to IL-4 by a cGMP increase through activation of an inducible NO synthase. Here, IL-4 was found to induce an accumulation of cGMP (1 – 3 min and cAMP (20 – 25 min in unstimulated monocytes. This was impaired with NOS inhibitors, but also with EGTA and calcium/calmodulin inhibitors. These results suggest that: (1 IL-4 may stimulate different NOS isoforms in resting and IFN-γ activated monocytes, and (2 cAMP accumulation may be partially dependent on the NO pathway. By RT-PCR, a type III constitutive NOS mRNA was detected in U937 monocytic cells. IL-4 also increased the [Ca2+]i in these cells. Different NOS may thus be expressed in monocytic cells depending on their differentiation and the signals they receive.

  15. IRS-1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells.

    Science.gov (United States)

    Wang, L M; Myers, M G; Sun, X J; Aaronson, S A; White, M; Pierce, J H

    1993-09-17

    Although several interleukin-3 (IL-3)-dependent cell lines proliferate in response to IL-4 or insulin, the 32D line does not. Insulin and IL-4 sensitivity was restored to 32D cells by expression of IRS-1, the principal substrate of the insulin receptor. Although 32D cells possessed receptors for both factors, they lacked the IRS-1--related protein, 4PS, which becomes phosphorylated by tyrosine in insulin- or IL-4--responsive lines after stimulation. These results indicate that factors that bind unrelated receptors can use similar mitogenic signaling pathways in hematopoietic cells and that 4PS and IRS-1 are functionally similar proteins that are essential for insulin- and IL-4--induced proliferation.

  16. 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.

  17. Association of polymorphisms in non-classic MHC genes with susceptibility to autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    JieTang; ChengZhou; Zhi-JunZhang; Shu-SenZheng

    2012-01-01

    BACKGROUND: Autoimmune hepatitis is a chronic, generally progressive inflammatory disorder of the liver, of which the cause is unclear. It was demonstrated that genetic factors are involved in its pathogenesis. Previous studies showed that human leukocyte antigen in the major histocompatibility complex (MHC) is associated with susceptibility to autoimmune hepatitis. Current genome scanning studies suggest that genes outside the MHC also play a critical role in autoimmune disorders. This article focuses on our current understanding of the polymorphisms of these genes and their roles in the pathogenesis of autoimmune hepatitis. DATA  SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords autoimmune hepatitis, polymorphism, CTLA-4, Fas, TNF-α, TGF-β1, TBX21 and VDR up to May 2011. Additional papers were identified by a manual search of the references from key articles. RESULTS:  According to the case-control studies on genetic polymorphisms, at least six genes (CTLA-4, Fas, TNF-α, TGF-β1, TBX21 and VDR) are involved in autoimmune hepatitis besides HLA. So far, there has been no agreement about gene susceptibility and the actual clinical significance of these genes is still controversial. CONCLUSION: Studies on gene polymorphisms outside the MHC and knowledge of genetic predispositions for autoimmune hepatitis may not only elucidate pathogenic mechanisms, but also provide new targets for therapy in the future.

  18. Surfactant protein B gene polymorphism in preterm babies with respiratory distress syndrome

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    P.P.R. Lyra

    2011-01-01

    Full Text Available The etiology of respiratory distress syndrome (RDS is multifactorial and multigenic. Studies have suggested that polymorphisms and mutations in the surfactant protein B (SP-B gene are associated with the pathogenesis of RDS. The objectives of this study were to determine and compare the frequencies of SP-B gene polymorphisms in preterm babies with and without RDS. We studied 151 neonates: 79 preterm babies without RDS and 72 preterm newborns with RDS. The following four SP-B gene polymorphisms were analyzed: A/C at -18, C/T at 1580, A/G at 9306, and G/C at nucleotide 8714. The polymorphisms were detected by PCR amplification of genomic DNA and genotyping. The genotypes were determined using PCR-based converted restriction fragment length polymorphisms. The control group consisted of 42 (53% girls and 37 (47% boys. Weight ranged from 1170 to 3260 g and mean gestational age (GA was 33.9 weeks (range: 29 to 35 weeks and 6 days. The RDS group consisted of 31 (43% girls and 41 (57% boys. Weight ranged from 614 to 2410 g and mean GA was 32 weeks (range: 26 to 35 weeks. The logistic regression model showed that GA was the variable that most contributed to the occurrence of RDS. The AG genotype of the A/G polymorphism at position 9306 of the SP-B gene was a protective factor in this population (OR = 0.1681; 95%CI = 0.0426-0.6629. We did not detect differences in the frequencies of the other polymorphisms between the two groups of newborns.

  19. Sudden infant death syndrome (SIDS) and polymorphisms in Monoamine oxidase A gene (MAOA): a revisit.

    Science.gov (United States)

    Groß, Maximilian; Bajanowski, Thomas; Vennemann, Mechtild; Poetsch, Micaela

    2014-01-01

    Literature describes multiple possible links between genetic variations in the neuroadrenergic system and the occurrence of sudden infant death syndrome. The X-chromosomal Monoamine oxidase A (MAOA) is one of the genes with regulatory activity in the noradrenergic and serotonergic neuronal systems and a polymorphism of the promoter which affects the activity of this gene has been proclaimed to contribute significantly to the prevalence of sudden infant death syndrome (SIDS) in three studies from 2009, 2012 and 2013. However, these studies described different significant correlations regarding gender or age of children. Since several studies, suggesting associations between genetic variations and SIDS, were disproved by follow-up analysis, this study was conducted to take a closer look at the MAOA gene and its polymorphisms. The functional MAOA promoter length polymorphism was investigated in 261 SIDS cases and 93 control subjects. Moreover, the allele distribution of 12 coding and non-coding single nucleotide polymorphisms (SNPs) of the MAOA gene was examined in 285 SIDS cases and 93 controls by a minisequencing technique. In contrast to prior studies with fewer individuals, no significant correlations between the occurrence of SIDS and the frequency of allele variants of the promoter polymorphism could be demonstrated, even including the results from the abovementioned previous studies. Regarding the SNPs, three statistically significant associations were observed which had not been described before. This study clearly disproves interactions between MAOA promoter polymorphisms and SIDS, even if variations in single nucleotide polymorphisms of MAOA should be subjected to further analysis to clarify their impact on SIDS.

  20. 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

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    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.

  1. Intron 1 and exon 1 alpha estrogen receptor gene polymorphisms in women with endometriosis.

    Science.gov (United States)

    Sato, Hélio; Nogueira-de-Souza, Naiara C; D'Amora, Paulo; Silva, Ismael D C G; Girão, Manoel J B C; Schor, Eduardo

    2008-12-01

    To evaluate the association of intron 1 and exon 1 polymorphisms in the estrogen receptor alpha gene (ER-alpha) with endometriosis in women. Association study. Endometriosis Unit, Federal University of São Paulo. The control group consisted of volunteers older than 45 years who had no evidence of endometriosis antecedents. Two groups with the disease were evaluated: the first group had stage I or II endometriosis and the second group stage III or IV. Polymerase chain reaction (PCR) followed by digestion with HaeIII and MspI endonucleases (RFLP) were applied to detect intron 1 and exon 1 polymorphisms, respectively, in a total of 125 controls and 105 affected women. Frequency and distribution of HaeIII and MspI polymorphisms in ER-alpha. No significant differences in the frequency of polymorphisms either in intron 1 or exon 1 of ER-alpha were found when endometriosis patients were compared with control subjects. Furthermore, the frequency of ER-alpha polymorphisms within the two different groups of patients with disease was statistically similar. The odds ratio between presence of intron 1 single-nucleotide polymorphisms (SNP) and endometriosis was 0.904, and the odds ratio between exon 1 SNP and endometriosis was 0.976. The evaluated polymorphisms were not associated with endometriosis.

  2. Do prion protein gene polymorphisms induce apoptosis in non-mammals?

    Indian Academy of Sciences (India)

    Tugce Birkan; Mesut Sahin; Zubeyde Oztel; Erdal Balcan

    2016-03-01

    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, V225A and M237V, were common in 15 out of 30 turtles; in one sample, three SNPs, L203V, N205I and M237V, and in the remaining 14 samples, only L203V and N205I polymorphisms, were investigated. Besides, C658T, C664T, C670A and C823A SNPs were silent mutations. To elucidate the relationship between the SNPs and apoptosis, TUNEL assays and active caspase-3 immunodetection techniques in brain sections of the polymorphic samples were performed. The results revealed that TUNEL-positive cells and active caspase-3-positive cells in the turtles with four polymorphisms were significantly increased compared with those of the turtles with two polymorphisms (P<0.01 and P<0.05, respectively). In conclusion, this study provides preliminary information about the possible relationship between SNPs within the Prnp locus and apoptosis in a non-mammalian species, Trachemys scripta, in which prion disease has never been reported.

  3. Functional polymorphisms in the P2X7 receptor gene are associated with osteoporosis

    DEFF Research Database (Denmark)

    Husted, L B; Harsløf, T; Stenkjær, L;

    2013-01-01

    -rays. RESULTS: The rare allele of a splice site polymorphism, 151 + 1: G-T, was associated with increased fracture risk and reduced BMD in women. Two other loss-of-function polymorphisms, Glu496Ala and Gly150Arg, were also associated with BMD. The Glu496Ala variant allele was associated with decreased lumbar......UNLABELLED: The P2X(7) receptor is an ATP-gated cation channel. We investigated the effect of both loss-of-function and gain-of-function polymorphisms in the P2X(7) receptor gene on BMD and risk of vertebral fractures and found that five polymorphisms and haplotypes containing three...... of these polymorphisms were associated with BMD and fracture risk. INTRODUCTION: The P2X(7) receptor is an ATP-gated cation channel. P2X(7) receptor knockout mice have reduced total bone mineral content, and because several functional polymorphisms have been identified in the human P2X(7) receptor gene, we wanted...

  4. Association of two polymorphisms of tumor necrosis factor gene with acute biliary pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Dian-Liang Zhang; Jie-Shou Li; Zhi-Wei Jiang; Bao-Jun Yu; Xing-Ming Tang; Hong-Mei Zheng

    2003-01-01

    AIM: To investigate TNF-α-308 and TNFB polymorphisms in acute biliary pancreatitis (ABP) and to related them to the plasma TNF-α levels.METHODS: Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients (n=127) and healthy controls (n=-102)using restriction fragment length polymorphism analysis of polymerase chain reaction (PCR) products. Reading the size of digested bands from polyacrylamide gel demonstrated the two alleles TNF1 and TNF2, or the two alleles TNFB1and TNFB2.RESULTS: The frequencies of TNF2 polymorphism and TNFB2 polymorphism were both similar in patients with mild or severe pancreatitis, so were in pancreatitis patients and in controls. Patients with septic shock showed a significantly higher prevalence of the TNF2 than those without. No significant differences were found in the genotype distribution of TNF-α-308 and TNFB among different groups. Plasma TNF-α levels did not differ significantly in ASBP patients displaying different alleles of the TNF gene studied.CONCLUSION: Results indicate that TNF gene polymorphisms studied play no part in determination of disease severity or susceptibility to acute biliary pancreatitis; however, TNF2polymorphism is associated with septic shock from ASBP.Genetic factors are not important in determining plasma TNF-α levels in ASBP.

  5. Association study of promoter polymorphisms at the dopamine transporter gene in Attention Deficit Hyperactivity Disorder

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    Huang Yu-Shu

    2009-02-01

    Full Text Available Abstract Background Attention deficit hyperactivity disorder (ADHD is a complex neurobehavioral disorder. The dopamine transporter gene (DAT1/SLC6A3 has been considered a good candidate for ADHD. Most association studies with ADHD have investigated the 40-base-pair variable number of tandem repeat (VNTR polymorphism in the 3'-untranslated region of DAT1. Only few studies have reported association between promoter polymorphisms of the gene and ADHD. Methods To investigate the association between the polymorphisms -67A/T (rs2975226 and -839C/T (rs2652511 in promoter region of DAT1 in ADHD, two samples of ADHD patients from the UK (n = 197 and Taiwan (n = 212 were genotyped, and analysed using within-family transmission disequilibrium test (TDT. Results A significant association was found between the T allele of promoter polymorphism -67A/T and ADHD in the Taiwanese population (P = 0.001. There was also evidence of preferential transmission of the T allele of -67A/T polymorphism in combined samples from the UK and Taiwan (P = 0.003. No association was detected between the -839C/T polymorphism and ADHD in either of the two populations. Conclusion The finding suggests that genetic variation in the promoter region of DAT1 may be a risk factor in the development of ADHD.

  6. Association of XPC Gene Polymorphisms with Susceptibility to Prostate Cancer: Evidence from 3,936 Subjects

    Science.gov (United States)

    Zou, Yan-Feng; Tao, Jin-Hui; Ye, Qian-Ling; Pan, Hai-Feng; Pan, Fa-Ming; Su, Hong

    2013-01-01

    Aim: Polymorphisms of xeroderma pigmentosum complementation group C (XPC) are thought to have significant effects on prostate cancer (PCa) risk. The aim of our study was to evaluate the impact of XPC gene polymorphisms on PCa risk by using a meta-analysis. Methods: Data were collected from the following electronic databases: PubMed, EMBASE, Elsevier Science Direct, Cochrane Library, and CNKI, with the last report up to April 30, 2013. Odds ratios with 95% confidence intervals were used to assess the strength of the association. Results: A total of five separate case–control studies (1966 cases and 1970 controls) were included in this meta-analysis. Meta-analysis was performed for the rs2228001 and PAT+/−polymorphisms. We did not detect a significant association between rs2228001 polymorphism and PCa (p>0.05). Similar results were found in stratification analyses by ethnicity and tumor stage. We detected a significant association of PAT+/−polymorphism with PCa (p0.05). Conclusion: These analyses suggest that XPC gene PAT+/−polymorphism, but not rs2228001, likely contributes to susceptibility to PCa. PMID:24093803

  7. GH gene polymorphisms and expression associated with egg laying in muscovy ducks (Cairina moschata).

    Science.gov (United States)

    Wu, X; Yan, M J; Lian, S Y; Liu, X T; Li, A

    2014-02-01

    Accumulated evidence suggests that the growth hormone (GH) gene plays a physiological role in the control of reproductive function. Here, we examined the correlation between egg-laying traits and GH gene polymorphisms and expression patterns in the muscovy duck (Cairina moschata). PCR single-strand conformation polymorphism was used to identify polymorphisms in intron 3 of GH. One single nucleotide polymorphism (g.3270 A > G) was detected by sequencing, and the frequencies of the A and G alleles in the population were 0.65 and 0.35, respectively. A comparison test showed that the AA genotype group had more consecutive laying days and more eggs at 300 days than the GG genotype group (P 0.05). Such a significant correlation between GH polymorphisms and egg-laying performance suggested that GH could be a candidate locus affecting the laying trait in muscovy duck. Furthermore, real-time fluorescent quantitative PCR demonstrated that GH is expressed in all selected tissues, but is highly expressed in the hypothalamic-pituitary-gonadal axis and heart. This unique expression pattern suggested that GH may exert its local physiological function through the autocrine or paracrine pathway during gonad development and growth in the muscovy duck. The data presented in this paper revealed GH polymorphisms and expression patterns in the muscovy duck and indicated a potential regulatory effect of GH on reproduction.

  8. Codon 129 polymorphism of prion protein gene in is not a risk factor for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Jerusa Smid

    2013-07-01

    Full Text Available Interaction of prion protein and amyloid-b oligomers has been demonstrated recently. Homozygosity at prion protein gene (PRNP codon 129 is associated with higher risk for Creutzfeldt-Jakob disease. This polymorphism has been addressed as a possible risk factor in Alzheimer disease (AD. Objective To describe the association between codon 129 polymorphisms and AD. Methods We investigated the association of codon 129 polymorphism of PRNP in 99 AD patients and 111 controls, and the association between this polymorphism and cognitive performance. Other polymorphisms of PRNP and additive effect of apolipoprotein E gene (ApoE were evaluated. Results Codon 129 genotype distribution in AD 45.5% methionine (MM, 42.2% methionine valine (MV, 12.1% valine (VV; and 39.6% MM, 50.5% MV, 9.9% VV among controls (p>0.05. There were no differences of cognitive performance concerning codon 129. Stratification according to ApoE genotype did not reveal difference between groups. Conclusion Codon 129 polymorphism is not a risk factor for AD in Brazilian patients.

  9. [Association analysis between polymorphisms of PON gene cluster with coronary heart disease in Chinese].

    Science.gov (United States)

    Wang, Xiao-Ling; Fan, Zhong-Jie; Huang, Jian-Feng; Su, Shao-Yong; Zhao, Jian-Gong; Gu, Dong-Feng

    2005-07-01

    An extensive association analysis of PON gene cluster (PONs) with coronary heart disease (CHD) was performed in Chinese Han population. Eleven polymorphisms of PON1, PON2 and PON3 gene were investigated for association with CHD in 474 male patients and 475 controls. Univariate analyses showed the cases had significantly higher frequencies of PON1 192Q allele, 160R allele, -162A allele and PON2 311C allele than were seen in the controls. Logistic regression analyses revealed only the PON1 R160G and -162G/A polymorphisms remained significantly associated with CHD (P = 0.0054 and P = 0.0002). Haplotype analyses for various polymorphism combinations further confirmed the results of individual polymorphism analyses. Only the frequencies of haplotypes containing -162A allele were significantly higher,whereas only the frequencies of haplotypes containing 160G allele significantly lower in cases than those in controls in various polymorphism combinations. This extensive association study has identified the PON1 -162G/A and R160G polymorphisms to be independently associated with CHD in Chinese Han population,and warrants further study to elucidate the biological mechanism.

  10. Detecting the polymorphism sites of p53 and Fas genes of Han population in Zhejiang province

    Institute of Scientific and Technical Information of China (English)

    Yang Zhuo; Xingye Zeng; Dadao Huang; Xuexue Zhou

    2006-01-01

    BACKGROUND: It is of significance for single nucleotide polymorphisms (SNPs),a difference of rank, which exists widely in biology, genetics and other fields.OBJECTIVE: To detect polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province.DESIGN: Simple random sampling.SETTING: Department of Surgery of the 118 Hospital of Chinese PLA.PARTICIPANTS: A total of 80 healthy people in Han nationality were selected from hospitals in Zhejiang province from August 2005 to January 2006. There were 43 males and 37 females aged from 3 to 78 years with the mean age of 39.5 years, and all subjects were consent. DNA which was used in genetic analysis was selected from peripheral venous blood of all subjects and maintained at -20 ℃.METHODS: Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene were detected with directly DNA sequencing technique.MAIN OUTCOME MEASURES: Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province.RESULTS: A total of 80 samples were involved in the final analysis. SNPs sites were found at the 119th base of exon-4 of p53 gene (the 72nd codon of p53 gene), the 670th base of upper start codon in promotor of Fas gene (Fas-670), and the 995th base of intron-7 of Fas gene, especially SNPs in the 995th base of intron-7 pf Fas gene, I.e. C→A transversion, was a new site.CONCLUSION: One unknown SNPs site is discovered in intron-7 of Fas gene of people in Han nationality in Zhejiang province. This study also proves that the 72nd codon exists in p53 gene and the -670 polymorphism site exists in promotor of Fas gene.

  11. Logistic regression models for polymorphic and antagonistic pleiotropic gene action on human aging and longevity

    DEFF Research Database (Denmark)

    Tan, Qihua; Bathum, L; Christiansen, L

    2003-01-01

    In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomous responses to handle the polymorphic...... situation. Genotype and allele-based parameterization can be used to investigate the modes of gene action and to reduce the number of parameters, so that the power is increased while the amount of multiple testing minimized. A binomial logistic regression model with fractional polynomials is used to capture...

  12. Relationship of PON1 192 and 55 gene polymorphisms to calcific valvular aortic stenosis

    DEFF Research Database (Denmark)

    Moura, Luis M; Faria, Susana; Brito, Miguel

    2012-01-01

    Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical and pathophy......Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical...... and pathophysiological risk factors of CAD and calcific aortic valve stenosis (CAVS), we postulated a link between PON1 alleles and CAVS progression....

  13. Bovine growth hormone gene polymorphism affects stress response in Japanese Black cattle.

    Science.gov (United States)

    Tachi, Noriko; Tanaka, Sigefumi; Ardiyanti, Astrid; Katoh, Kazuo; Sato, Shusuke

    2014-06-01

    We investigate the associations between growth hormone (GH) gene polymorphism and behavioral and physiological responses to stressors and learning ability in Japanese Black cattle. Flight distance test was conducted in the first experiment. Steers with haplotype C of GH gene polymorphism avoided human approaches at a significantly greater distance than ones without haplotype C (C: 1.9 ± 0.9, non-C: 1.0 ± 0.2 m, P affect stress responses through GH concentration in steers.

  14. Heat shock protein 70 gene polymorphisms are associated with paranoid schizophrenia in the Polish population

    OpenAIRE

    2013-01-01

    HSP70 genes have been considered as promising schizophrenia candidate genes based on their protective role in the central nervous system under stress conditions. In this study, we analyzed the potential implication of HSPA1A +190G/C, HSPA1B +1267A/G, and HSPA1L +2437T/C polymorphisms in the susceptibility to paranoid schizophrenia in a homogenous Caucasian Polish population. In addition, we investigated the association of the polymorphisms with the clinical variables of the disease. Two hundr...

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

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    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.

  16. Detection of an exon 53 polymorphism in the dystrophin gene.

    Science.gov (United States)

    Prior, T W; Papp, A C; Snyder, P J; Sedra, M S

    1993-10-01

    We utilized a heteroduplex method to screen for small mutations in Duchenne muscular dystrophy patients who did not have deletions or duplications. A dystrophin exon 53 heteroduplex band was identified in 14.4% of the affected patients. Direct sequencing of the amplified product from DNA producing the heteroduplex revealed the presence of a polymorphism in the coding region. The codon for asparagine was converted from AAT to AAC.

  17. A Candidate Gene Association Study of 77 Polymorphisms in Migraine

    OpenAIRE

    Schürks, Markus; Kurth, Tobias; Buring, Julie E.; Zee, Robert Y.L.

    2009-01-01

    Population-based studies have established an association between migraine and cardiovascular disease (CVD). We sought to investigate whether genetic variants implicated in CVD are associated with migraine. We performed an association study among 25,713 women, participating in the Women’s Health Study, with information on 77 previously characterized polymorphisms. Migraine and migraine aura status were self-reported. We used logistic regression to investigate the genotype-migraine association....

  18. No linkage and association of atopy to chromosome 16 including the interleukin-4 receptor gene

    DEFF Research Database (Denmark)

    Haagerup, A; Bjerke, T; Schiøtz, P O

    2001-01-01

    BACKGROUND: Several susceptibility genes for atopy have been suggested in recent years. Few have been investigated as intensively as the interleukin-4-receptor alpha (IL4Ralpha) gene on chromosome 16. The results remain in dispute. Therefore, in a robust design, we tested for association of type I...... and evaluated by the transmission disequilibrium test (TDT). Multipoint linkage analysis and exclusion mapping were conducted with sib-pairs analyzed for 17 microsatellite markers. RESULTS: No evidence for association or linkage to the IL4R polymorphisms was found (P values: 0.12-0.90). Linkage analysis did...

  19. A FQ-RT-PCR method for quantitative determination of IL-2 mRNA and IL-4 mRNA and its application

    Institute of Scientific and Technical Information of China (English)

    QING HUI ZHU; QING LU; GU SHENG ZHANG

    2006-01-01

    The purpose of the study is to establish a fluorescence quantitative reverse transcription polymerase chain response (FQ-RT-PCR) method for the quantitative determination of IL-2 mRNA and IL-4mRNA in Th cells, with which the Th cells status of the patients with gynaecological tumors and chronic renal failure (CRF) can be analyzed. IL-2 cDNA and IL-4 cDNA were prepared, and the plasmid pMD18 carrying IL-2 cDNA or IL-4 cDNA fragment was constructed and cloned as the template for quantitative determination. The primers and probes labelled with 6-carboxy-fluorescein (FAM) and 6-carboxytetramethylrhodamine (TAMRA) were prepared, and the experimental conditions were optimized to set up the FQ-RT-PCR method for quantitative determination of IL-2 mRNA and IL-4 mRNA. Th cells enriched from peripheral blood mononuclear cells (PBMCs) of 20 healthy volunteers (HVs), 16 gynaecological benign (GB) cases, 18 gynaecological malignant (GM) tumor cases and 16 chronic renal failure (CRF) patients were tested for IL-2 mRNA and IL-4 mRNA by FQ-RT-PCR. The house-keeping gene 3-actin was used as the internal control gene of the experiment. The standard curve for log concentration of series of quantitative templates vs threshold cycle (CT) was established by linear regression, and the linear range was 102-107 copies/μl. The imprecision test showed the CV of inter-assay and intra-assay of a high content sample by FQ-RT-PCR were 7.8% and 12.5%, respectively. The CV of inter-assay and intra-assay of a low content sample were 10.8% and 19.5%, respectively. The IL-2 mRNA expressions in Th of the patients with gynaecological malignant tumor (compared with the HVs and the patients with gynaecological benign disease) and in Th of the CRF patients (compared with the HVs) were declined significantly and at the same time the IL-4 mRNA expression increased significantly ( P < 0. 001 ). A simple, sensitive and accurate FQ-RT-PCR method for the quantitative detection of IL-2 mRNA and IL-4 mRNA has

  20. Allelic Polymorphism, Gene Duplication and Balancing Selection of MHC Class IIB Genes in the Omei Treefrog (Rhacophorus omeimontis)

    Institute of Scientific and Technical Information of China (English)

    Li HUANG; Mian ZHAO; Zhenhua LUO; Hua WU

    2016-01-01

    The worldwide declines in amphibian populations have largely been caused by infectious fungi and bacteria. Given that vertebrate immunity against these extracellular pathogens is primarily functioned by the major histocompatibility complex (MHC) class II molecules, the characterization and the evolution of amphibian MHC class II genes have attracted increasing attention. The polymorphism of MHC class II genes was found to be correlated with susceptibility to fungal pathogens in many amphibian species, suggesting the importance of studies on MHC class II genes for amphibians. However, such studies on MHC class II gene evolution have rarely been conducted on amphibians in China. In this study, we chose Omei treefrog (Rhacophorus omeimontis), which lived moist environments easy for breeding bacteria, to study the polymorphism of its MHC class II genes and the underlying evolutionary mechanisms. We amplified the entire MHC class IIB exon 2 sequence in the R. omeimontis using newly designed primers. We detected 102 putative alleles in 146 individuals. The number of alleles per individual ranged from one to seven, indicating that there are at least four loci containing MHC class IIB genes in R. omeimontis. The allelic polymorphism estimated from the 102 alleles in R. omeimontis was not high compared to that estimated in other anuran species. No significant gene recombination was detected in the 102 MHC class IIB exon 2 sequences. In contrast, both gene duplication and balancing selection greatly contributed to the variability in MHC class IIB exon 2 sequences of R. omeimontis. This study lays the groundwork for the future researches to comprehensively analyze the evolution of amphibian MHC genes and to assess the role of MHC gene polymorphisms in resistance against extracellular pathogens for amphibians in China.

  1. Catechol-O-Methyltransferase gene val158met polymorphism and depressive symptoms during early childhood

    Science.gov (United States)

    Sheikh, Haroon I.; Kryski, Katie R.; Smith, Heather J.; Dougherty, Lea R.; Klein, Daniel N.; Bufferd, Sara J.; Singh, Shiva M.; Hayden, Elizabeth P.

    2017-01-01

    Catechol-O-Methyltransferase (COMT) is a critical regulator of catecholamine levels in the brain. A functional polymorphism of the COMT gene, val158met, has been linked to internalizing symptoms (i.e., depression and anxiety) in adolescents and adults. We extended this research by investigating whether the val158met polymorphism was associated with childhood symptoms of depression and anxiety in two independent samples of young children (Ns = 476 and 409). In both samples, preschool-aged children were genotyped for the COMT val158met polymorphism. Symptoms of psychopathology were assessed via parent interviews and primary caregiver reports. In both samples, children homozygous for the val allele had higher levels of depressive symptoms compared to children with at least one copy of the met allele. Our findings extend previous research in older participants by showing links between the COMT val158met polymorphism and internalizing symptoms in early childhood. PMID:23475824

  2. Polymorphisms in inflammation genes, tobacco smoke and furred pets and wheeze in children

    DEFF Research Database (Denmark)

    Sorensen, M.; Allermann, L.; Vogel, Ulla Birgitte

    2009-01-01

    Persistent wheeze in childhood is associated with airway inflammation. The present study investigated relationships between polymorphisms in inflammatory genes, exposure to tobacco smoke and furred pets and risk of recurrent wheeze in children. Within a birth cohort of 101,042 children we...... on number of episodes with wheeze (18 months), exposure to tobacco smoke and pet-keeping. Recurrent wheeze was defined as at least four episodes of wheeze before the child was 18 months old. There was a statistically significant association between the IL-13 Arg144Gln polymorphism and risk of recurrent...... wheeze (p = 0.01). Furthermore, there was a statistically significant interaction between this polymorphism and exposure to tobacco smoke during pregnancy, though this was probably a chance finding. There were no other statistically significant effects of the polymorphisms or interactions with exposure...

  3. Modulation of mouse macrophage polarization in vitro using IL-4 delivery by osmotic pumps.

    Science.gov (United States)

    Pajarinen, Jukka; Tamaki, Yasunobu; Antonios, Joseph K; Lin, Tzu-Hua; Sato, Taishi; Yao, Zhenyu; Takagi, Michiaki; Konttinen, Yrjö T; Goodman, Stuart B

    2015-04-01

    Modulation of macrophage polarization is emerging as promising means to mitigate wear particle-induced inflammation and periprosthetic osteolysis. As a model for continuous local drug delivery, we used miniature osmotic pumps to deliver IL-4 in order to modulate macrophage polarization in vitro from nonactivated M0 and inflammatory M1 phenotypes towards a tissue regenerative M2 phenotype. Pumps delivered IL-4 into vials containing mouse bone marrow macrophage (mBMM) media. This conditioned media (CM) was collected at seven day intervals up to four weeks (week 1 to week 4 samples). IL-4 concentration in the CM was determined by ELISA and its biological activity was assayed by exposing M0 and M1 mBMMs to week 1 or week 4 CM. The IL-4 concentration in the CM approximated the mathematically calculated amount, and its biological activity was well retained, as both M0 and M1 macrophages exposed to either the week 1 or week 4 CM assumed M2-like phenotype as determined by qRT-PCR, ELISA, and immunocytochemistry. The results show that IL-4 can be delivered using osmotic pumps and that IL-4 delivered can modulate macrophage phenotype. Results build a foundation for in vivo studies using our previously validated animal models and provide possible strategies to locally mitigate wear particle-induced macrophage activation and periprosthetic osteolysis.

  4. IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection

    Science.gov (United States)

    Hoving, Jennifer C.; Nieuwenhuizen, Natalie; McSorley, Henry J.; Ndlovu, Hlumani; Bobat, Saeeda; Kimberg, Matti; Kirstein, Frank; Cutler, Anthony J.; DeWals, Benjamin; Cunningham, Adam F.; Brombacher, Frank

    2013-01-01

    In this study, B cell function in protective TH2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα−/− mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4+ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88−/− B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4+ T cell-mediated protective immunity against N. brasiliensis infection. PMID:24204255

  5. IL-4 Deficiency Decreases Mortality but Increases Severity of Arthritis in Experimental Group B Streptococcus Infection

    Directory of Open Access Journals (Sweden)

    Luciana Tissi

    2009-01-01

    Full Text Available IL-4 is an anti-inflammatory cytokine that inhibits the onset and severity in different experimental arthritis models. Group B streptococci (GBS have been recognized as an ever-growing cause of serious invasive infections in nonpregnant adults. Septic arthritis is a clinical manifestation of GBS infection. To investigate the role of IL-4 in experimental GBS infection, IL-4 deficient or competent mice were inoculated with 1×107 GBS/mouse. Mortality, appearance of arthritis, GBS growth in the organs, and local and systemic cytokine and chemokine production were examined. IL-4–/– mice showed lower mortality rates but increased severity of arthritis and exhibited a lower microbial load in blood, kidneys, and joints than wt mice. Increased local levels of IL-1 β, IL-6, TNF-α, MIP-1α, and MIP-2 accompanied the more severe arthritis in IL-4–/– mice. Our results suggest a detrimental role of IL-4 in GBS sepsis, whereas it plays a beneficial effect on GBS-induced arthritis.

  6. TRANSFORMING GROWTH FACTOR Β1 C-509T GENE POLYMORPHISM IN PATIENTS WITH BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    Milena Despotović

    2014-12-01

    Full Text Available Bronchial asthma is a poligenic disorder caused by the influence of genetic and envioromental factors. The functional single nucleotide polymorphism (SNPs in the regulatory regions of the cytokine genes may affect the cytokine production and thus play a contributory role in the pathogenesis of asthma. Substitution of cytosine (C by thymine (T at the position -509 in the promoter region of the transforming growth factor β1 (TGF-β1 gene could be associated with asthma. The aim of this study was to investigate the association of the TGF-β1 C-509T polymorphism with asthma and to determine the distribution of this polymorphism in the Serbian population. A total of 57 patients with diagnosed asthma and 49 healthy controls were screened for TGF-β1 C-509T polymorphisms using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP method. The TGF-β1 C-509T genotype (p=0.413 and allele frequencies (p=0.227 distributions in patients did not reveal statistically significant difference compared to controls. Additionally, no difference in genotype and allele frequencies distribution between male and female subjects was observed. In conclusion, to the best knowledge of the authors, this is the first study examining the association of TGF-β1 C-509T polymorphism in the Serbian patients with asthma. The present study did not confirm the specific role of TGF-β1 C-509T polymorphisms in asthma. No differences in the distribution of TGF-β1 C-509T polymorphism between patients and healthy subjects were observed.

  7. Glucocorticoid receptor gene polymorphisms and potential association to chronic obstructive pulmonary disease susceptibility and severity

    Directory of Open Access Journals (Sweden)

    Schwabe K

    2009-12-01

    Full Text Available Abstract Objective As chronic obstructive pulmonary disease (COPD is known for poor glucocorticoid (GC response, we hypothesized that polymorphic variants of the glucocorticoid receptor (GR gene might predispose for COPD and/or disease severity. Materials and methods Three out of about 50 of the most abundant receptor GR gene polymorphisms were investigated in a case-control study which included 207 patients with chronic bronchitis or COPD (mean FEV1 50.5% predicted, GOLD I-IV and 106 age matched healthy subjects (mean FEV1 101.8% predicted. These were genotyped: a for the N363S (Exon 2; 1220 A > G (I; b the BCLI restriction fragment length polymorphism (Intron 2; 647 C > G (II; and c the ER2223EK (Exon 2; 198, 200 G > A (III, using RT-PCR and PCR-RFLP method on genomic DNA isolated from EDTA blood. Results Genotype distribution between COPD and healthy subjects were alike in all of these three polymorphisms. N363S was found in 0.94% of the healthy and 0% of the COPD subjects. BCLI was detected in 11.3% of the controls and 15.5% of the COPD patients whereas heterozygote frequency was less in the COPD (44.4% group (controls 60.4%. ER2223EK lacks in any of the study subjects. Further, SNPs did not correlate with COPD severity stage (GOLD, exacerbation rates, and clinical course. Conclusion COPD is not linked to gene polymorphisms N363S, BCLI-RFLP, and ER2223EK. Since we analyzed only these 3 receptor gene polymorphisms, this study cannot rule out that other GR gene variants and linkages may be of influence.

  8. Tumor necrosis factor gene polymorphisms and endometriosis in Asians: a systematic review and meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Lyu Jiangtao; Yang Hua; Lang Jinghe; Tan Xianjie

    2014-01-01

    Background Numerous studies have described the association between polymorphisms in the tumor necrosis factor (TNF) gene and risk of endometriosis.However,the results remain controversial.Here we reviewed studies reporting the association between TNF gene polymorphisms and endometriosis risk in Asians.Methods PubMed and Embase were searched.Twelve case-control studies assessing the role of multiple TNF gene polymorphisms in endometriosis were included.If no less than two articles evaluated one variant,meta-analysis was conducted; otherwise,narrative analysis was chosen.A fixed-or random-effects model was employed according to the heterogeneity among studies.The strength of the association between TNF gene polymorphisms and endometriosis risk was assessed by odds ratios and 95% confidence intervals.Results For TNF-α-238G>A,-308G>A,-857C>T,and-863C>A,no significant associations were identified from all genetic models.For TNF-α-850T>C,results from one study showed that patients harboring the heterozygote TC were less susceptible to endometriosis than patients harboring the homozygote TT.For TNF-α-1031T>C,a mild increase in endometriosis risk was found in the Asian population.Meta-analysis from two studies found that the TNF-β +252>G polymorphism had a protective effect in Chinese individuals.Due to the limitations of the included studies,it is necessitated to perform more studies to elucidate the possible roles of TNF gene polymorphisms in the pathogenesis of endometriosis.Conclusions TNF-α-1031T>C and TNF-β +252A>G were significantly associated with the risk of endometriosis in Asian and Chinese populations,respectively.To further evaluate these associations,more large-scale,rigorously designed studies are needed.

  9. Effect of candidate gene polymorphisms on reproductive traits in a Large White pig population.

    Science.gov (United States)

    Sato, Shuji; Kikuchi, Takashi; Uemoto, Yoshinobu; Mikawa, Satoshi; Suzuki, Keiichi

    2016-12-01

    The objective of this study was to test for association of candidate single nucleotide polymorphisms (SNPs) with sow prolificacy reproductive traits, such as litter size, ovulation rate and lifetime performance, in gilts of a Large White pig population. Preliminary research on 25 animals selected from the high- and low-performance groups of 347 animals with case-control studies indicated that seven genes were associated with total number of piglets born (TNB). Six of the seven genes were associated with reproductive traits, including TNB, number of piglets born alive (NBA) and average weight of piglet weaning (AWW). A MBL2 SNP was significantly associated with TNB and NBA in first parity. A CFB SNP was associated with TNB in first parity. An ACE SNP was associated with TNB in first and second parities. An EGF polymorphism was associated with TNB, NBA and AWW in second parity. A KCNC2 polymorphism was significantly associated with TNB and NBA in second parity. A SLC22A5 SNP was associated with TNB and NBA in second parity. Six candidate SNPs were associated with TNB; the only exception was a PRKAG3 polymorphism. A candidate gene approach enables some of these polymorphisms to be used in genetic improvement programs based on marker-assisted selection. © 2016 Japanese Society of Animal Science.

  10. CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD).

    Science.gov (United States)

    Wang, Peng; Yang, Yanjie; Yang, Xiuxian; Qiu, Xiaohui; Qiao, Zhengxue; Wang, Lin; Zhu, Xiongzhao; Sui, Hong; Ma, Jingsong

    2015-01-01

    Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population.

  11. Dopamine D2 receptor gene -141C Insertion/Deletion polymorphism in Turkish schizophrenic patients.

    Science.gov (United States)

    Kurt, Hulyam; Dikmen, Miris; Basaran, Ayşe; Yenilmez, Cinar; Ozdemir, Figen; Degirmenci, Irfan; Gunes, Hasan Veysi; Kucuk, Meral Urhan; Mutlu, Fezan

    2011-02-01

    Schizophrenia is a chronic and neuropsychiatric disease that affects about 0.5-1% of the world's population. An increase in dopamine and dopamine D2 receptor (DRD2) gene products has been well described in schizophrenic patients. Several groups have studied the relationship between dopaminergic hyperactivity and cellular communications have obtained discordant results. Studies searching for the relationship between the schizophrenia and DRD2 gene have gained more interest. Our objective was to determine the relationships among schizophrenic symptoms in schizophrenia subtypes and severity of symptoms in terms of DRD2 gene -141C Insertion/Deletion [Ins/Del; I/D] polymorphism by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) assay method. Genomic DNA was prepared from peripheral blood by using salt extraction method. After amplification of genomic DNA, PCR products were digested with BstNI restriction enzyme for the detection of DRD2 gene -141C Ins/Del polymorphism in 73 schizophrenic patients and 60 healthy control subjects. The allelic frequencies of the DRD2 gene -141C Ins/Del polymorphism in case and control groups were 79.5 and 77.5% for I allele; 20.5 and 22.5% for D allele respectively. There was no significant difference in frequencies of genotypes and alleles between the two groups. In schizophrenic and control subjects, there were no significant relationship in severity of the disease and schizophrenia types among the -141C Ins/Del genotypes and alleles.

  12. Association of polymorphisms of interleukin-18 gene promoter region with polycystic ovary syndrome in chinese population

    Directory of Open Access Journals (Sweden)

    Li Mei-zhi

    2010-10-01

    Full Text Available Abstract Background Recent research shows that polycystic ovary syndrome (PCOS may have an association with low-grade chronic inflammation, and that PCOS may induce an increase in serum interleukin-18 (IL-18 levels. Methods To investigate the polymorphisms of the IL-18 gene promoters with PCOS, two single nucleotide polymorphisms (SNPs in the promoter of the IL-18 gene (at positions -607C/A and -137G/C in 118 Chinese women with PCOS and 79 controls were evaluated using polymerase chain reaction (PCR. Results No significant differences were found in the genotype distribution, allele frequency and haplotype frequency between the PCOS and control groups. Further analysis demonstrated a relationship between IL-18 gene promoter polymorphisms and PCOS insulin resistance (IR. Regarding the -137 allele frequency, G and C allele frequencies were 93.5% and 6.5%, respectively, in the PCOS with IR patients; G and C allele frequencies were 85.4% and 14.6%, respectively, in PCOS patients without IR (chi2 = 3.601, P = 0.048. Conclusions The presence of a polymorphism in the IL-18 gene was found to have no correlation with the occurrence of PCOS. Carriage of the C allele at position -137 in the promoter of the IL-18 gene may play a protective role from the development of PCOS IR.

  13. 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.

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

    Science.gov (United States)

    Yizhou, Mei; Bei, He; Huilong, Li; Xin, Wang; Rui, Hu; Lu, Li

    2017-01-01

    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. PMID:28133421

  15. Association between polymorphisms of the insulin-degrading enzyme gene and late-onset Alzheimer disease.

    Science.gov (United States)

    Wang, Shitao; He, Feiyan; Wang, Ying

    2015-06-01

    The insulin-degrading enzyme (IDE) gene is a strong positional and biological candidate for late-onset Alzheimer disease (LOAD) susceptibility, with recent studies independently demonstrating an association between IDE gene variants and LOAD. However, previous data have been controversial. To investigate the relationship between IDE gene polymorphisms and LOAD risk, a case-control association study of 406 Han Chinese participants in Xinjiang, China, was undertaken. The LOAD and control groups consisted of 202 and 204 participants, respectively. The single-nucleotide polymorphisms rs1887922 and rs1999764 of the IDE gene were linked to LOAD incidence. The presence of the CT+CC genotype of rs1999764 had a protective effect compared to the TT genotype (adjusted P=.0001; odds ratio [OR]=0.226; 95% confidence interval [CI]=0.116-0.441), while the CT+CC genotype of rs1887922 was associated with increased LOAD risk (adjusted P=.0001; OR=3.640; 95% CI=1.889-7.016). Moreover, the effects of rs1887922 and rs1999764 were associated with LOAD risk independent of the apolipoprotein E ∊4 polymorphism and were more significant in men and women, respectively. These results demonstrate that the polymorphisms rs1887922 and rs1999764 of the IDE gene are associated with LOAD susceptibility in the Xinjiang Han population.

  16. Three types of polymorphisms in exon 14 in porcine Mx1 gene.

    Science.gov (United States)

    Morozumi, T; Sumantri, C; Nakajima, E; Kobayashi, E; Asano, A; Oishi, T; Mitsuhashi, T; Watanabe, T; Hamasima, N

    2001-08-01

    Much is known about the antiviral activity of Mx proteins in species such as mouse and human. In the mouse, loss of resistability to influenza virus has been shown to be due to specific polymorphisms in the Mx gene. This gene is therefore an interesting candidate gene for disease resistance in farm animals. The porcine Mx1 gene has already been identified and characterized based on its homology with mouse Mx1; however, until now no evidence of polymorphisms in the porcine gene has been reported. In this study, we have found two new polymorphisms in exon 14 of porcine Mx1 by DNA sequencing and confirmed their presence in different breeds, using polymerase chain reaction (PCR)-restriction fragment length polymorphisms (RFLP) with NarI and NaeI restriction enzymes. On the basis of the deduced amino acid sequence, one allele contains a deletion that may result in a frameshift to yield several amino acid substitutions and extension of the carboxyl terminal region of Mx1 protein. The deletion allele, Mx1c, was found to be segregating in Landrace, Berkshire, Duroc, Hampshire, and Yucatan miniature pig. A second point mutation, Mx1b, was detected in Meishan and two Vietnamese native pig breeds. All other breeds tested were fixed for the Mx1a allele that is identical to the sequence reported previously. It will be interesting to determine if the Mx1c deletion is associated with variation in resistance to the myxovirus family in the pig.

  17. TS Gene Polymorphisms Are Not Good Markers of Response to 5-FU Therapy in Stage III Colon Cancer Patients

    Directory of Open Access Journals (Sweden)

    A. Fariña-Sarasqueta

    2010-01-01

    Full Text Available Aim: Although the predictive and prognostic value of thymidylate synthase (TS expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy.

  18. Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice.

    Directory of Open Access Journals (Sweden)

    Saskia Schmidt

    Full Text Available Gut-dwelling helminthes induce potent IL-4 and IL-13 dominated type 2 T helper cell (T(H2 immune responses, with IL-13 production being essential for Nippostrongylus brasiliensis expulsion. This T(H2 response results in intestinal inflammation associated with local infiltration by T cells and macrophages. The resulting increased IL-4/IL-13 intestinal milieu drives goblet cell hyperplasia, alternative macrophage activation and smooth muscle cell hypercontraction. In this study we investigated how IL-4-promoted T cells contributed to the parasite induced effects in the intestine. This was achieved using pan T cell-specific IL-4 receptor alpha-deficient mice (iLck(creIL-4Rα(-/lox and IL-4Rα-responsive control mice. Global IL-4Rα(-/- mice showed, as expected, impaired type 2 immunity to N. brasiliensis. Infected T cell-specific IL-4Rα-deficient mice showed comparable worm expulsion, goblet cell hyperplasia and IgE responses to control mice. However, impaired IL-4-promoted T(H2 cells in T cell-specific IL-4Rα deficient mice led to strikingly reduced IL-4 production by mesenteric lymph node CD4(+ T cells and reduced intestinal IL-4 and IL-13 levels, compared to control mice. This reduced IL-4/IL-13 response was associated with an impaired IL-4/IL-13-mediated smooth muscle cell hypercontractility, similar to that seen in global IL-4Rα(-/- mice. These results demonstrate that IL-4-promoted T cell responses are not required for the resolution of a primary N. brasiliensis infection. However, they do contribute significantly to an important physiological manifestation of helminth infection; namely intestinal smooth muscle cell-driven hypercontractility.

  19. Evaluation of leptin level and Ob gene polymorphism in patients with Behcet's disease.

    Science.gov (United States)

    Okudan, Nilsel; Acar, Hasan; Gökbel, Hakki; Mevlitoğlu, Inci; Sari, Fatih

    2006-08-01

    The present study was aimed to evaluate serum leptin level and the frequency of oligopolymorphic codon 25 (CAA/CAG) of Ob gene in Behcet's disease. Eighty-seven patients with Behcet's disease and 85 healthy controls with matched age, gender and body mass index were included in the study. Serum leptin level was determined and genotype of codon 25 of Ob gene was performed by using the PCR amplification after DNA extraction. Serum leptin concentration of the patients with Behcet's disease (23.8 +/- 22.8 ng/ml) was higher than that of the control groups (17.1 +/- 14.7 ng/ml). The patients with Behcet's disease and control subjects showed CAA/CAA genotype, indicating the presence of no polymorphism. Neither Behcet's disease nor serum leptin level was found to be related to codon 25 polymorphism. We concluded that leptin 25CAG polymorphism is not associated with Behcet's disease and serum leptin level.

  20. NRAMP1 and VDR Gene Polymorphisms in Susceptibility to Tuberculosis in Venezuelan Population

    Science.gov (United States)

    Fernández-Mestre, Mercedes; Villasmil, Ángel; Takiff, Howard; Fuentes Alcalá, Zhenia

    2015-01-01

    Natural resistance-associated macrophage protein (Nramp1) and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis, and associations between susceptibility to tuberculosis and polymorphisms in the genes NRAMP and VDR have been sought in geographically diverse populations. We investigated associations of NRAMP1 and VDR gene polymorphisms with susceptibility to TB in the Venezuelan population. The results suggest the absence of any association between VDR variants FokI, ApaI, and TaqI and susceptibility to tuberculosis. In contrast, the NRAMP1 3′UTR variants were associated with susceptibility to M. tuberculosis infection, as seen in the comparisons between TST+ and TST− controls, and also with progression to TB disease, as shown in the comparisons between TB patients and TST+ controls. This study confirms the previously described association of the NRAMP1 3′UTR polymorphism with M. tuberculosis infection and disease progression. PMID:26578819

  1. [Research advances in gene polymorphisms in biological pathways of drugs for asthma].

    Science.gov (United States)

    Guo, Dan-Dan; Zheng, Xiang-Rong

    2016-06-01

    The studies on gene polymorphisms in biological pathways of the drugs for the treatment of asthma refer to the studies in which pharmacogenetic methods, such as genome-wide association studies, candidate gene studies, genome sequencing, admixture mapping analysis, and linkage disequilibrium, are used to identify, determine, and repeatedly validate the effect of one or more single nucleotide polymorphisms on the efficacy of drugs. This can provide therapeutic strategies with optimal benefits, least side effects, and lowest costs to patients with asthma, and thus realize individualized medicine. The common drugs for asthma are β2 receptor agonists, glucocorticoids, and leukotriene modifiers. This article reviews the research achievements in polymorphisms in biological pathways of the common drugs for asthma, hoping to provide guidance for pharmacogenetic studies on asthma in future and realize individualized medicine for patients with asthma soon.

  2. Study on relationship of apolipoprotein E gene polymorphism and genetic susceptibility of stress urinary incontinence

    Institute of Scientific and Technical Information of China (English)

    Tong Jia-li; Lang Jing-he; Zhu lan

    2010-01-01

    Objective: To explore the relationship between apolipoprotein E (ApoE) gene polymorphism and susceptibility of stress urinary incontinence (SUI).Methods: ApoE genotypes were examined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) technique in 99 patients with SUI and 101 asymptomatic controls. Results: The frequency of allele e3 of ApoE was slightly lower in patients with anatomic SUI than that in controls (79.44% vs. 81.68%), while the frequency of allele e4 of ApoE was slightly higher in patients with anatomic SUI than that in controls (10.00% vs. 9.90%). No significant difference was found in frequency of allele e3 or e4 between SUI patients and controls (χ2=0.523, P=0.770).Conclusion: The gene polymorphism of ApoE is not independently involved in the development of SUI.

  3. NRAMP1 and VDR Gene Polymorphisms in Susceptibility to Tuberculosis in Venezuelan Population

    Directory of Open Access Journals (Sweden)

    Mercedes Fernández-Mestre

    2015-01-01

    Full Text Available Natural resistance-associated macrophage protein (Nramp1 and the vitamin D receptor (VDR are central components of the innate and adaptive immunity against Mycobacterium tuberculosis, and associations between susceptibility to tuberculosis and polymorphisms in the genes NRAMP and VDR have been sought in geographically diverse populations. We investigated associations of NRAMP1 and VDR gene polymorphisms with susceptibility to TB in the Venezuelan population. The results suggest the absence of any association between VDR variants FokI, ApaI, and TaqI and susceptibility to tuberculosis. In contrast, the NRAMP1 3′UTR variants were associated with susceptibility to M. tuberculosis infection, as seen in the comparisons between TST+ and TST− controls, and also with progression to TB disease, as shown in the comparisons between TB patients and TST+ controls. This study confirms the previously described association of the NRAMP1 3′UTR polymorphism with M. tuberculosis infection and disease progression.

  4. An IL-4R alpha allelic variant, I50, acts as a gain-of-function variant relative to V50 for Stat6, but not Th2 differentiation.

    Science.gov (United States)

    Stephenson, Linda; Johns, Mary H; Woodward, Emily; Mora, Ana L; Boothby, Mark

    2004-10-01

    Signaling through the IL-4R alpha-chain (IL-4Ralpha) is crucial for the development of Th2 cells, central effectors in atopic disease. Alleles of the IL-4Ralpha have been identified that have been variably associated with increased incidence of allergic disease, but there is little direct evidence that any variant is sufficient to alter a target that determines allergic pathophysiology or susceptibility. Variants of IL-4Ralpha encoding isoleucine instead of valine at position 50 (I50 vs V50, respectively) can signal increased Stat6-dependent transcriptional activity, whether in an I50, Q551 or I50, R551 haplotype. Strikingly, signaling through these receptors did not increase the efficiency of Th2 development or the IL-4 mediated repression of Th1 development or a target gene, IL-18Ralpha. Further, IL-4-induced proliferation was similar for Th2 cells independent of the variant expressed. Together these findings indicate that IL-4Ralpha variants that exhibit gain-of-function with respect to Stat6 do not act directly through alterations in Th2/Th1 induction after Ag exposure. The data further suggest that for such variants, any mechanistic involvement is based on a role in cellular targets of Th2 cytokines.

  5. IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1

    Science.gov (United States)

    Ruckerl, Dominik; Thomas, Graham D.; Hewitson, James P.; Duncan, Sheelagh; Brombacher, Frank; Maizels, Rick M.; Hume, David A.; Allen, Judith E.

    2013-01-01

    Macrophages (MΦs) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation of resident cells. We recently revealed a major role for IL-4 in the proliferative expansion of resident MΦs during a Th2-biased tissue nematode infection. We now show that proliferation of MΦs during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires MΦ-intrinsic IL-4R signaling. However, both IL-4Rα–dependent and –independent mechanisms contributed to MΦ proliferation during nematode infections. IL-4R–independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4Rα expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4Rα+ compared with IL-4Rα− cells. Mechanistically, this occurred by conversion of IL-4Rα+ MΦs from a CSF-1–dependent to –independent program of proliferation. Thus, IL-4 increases the relative density of tissue MΦs by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4Rα signaling triggered proliferation above homeostatic levels, only CSF-1 led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident MΦ numbers without coincident monocyte recruitment. PMID:24101381

  6. Relation between sonic hedgehog pathway gene polymorphisms and basal cell carcinoma development in the Polish population.

    Science.gov (United States)

    Lesiak, Aleksandra; Sobolewska-Sztychny, Dorota; Majak, Paweł; Sobjanek, Michał; Wodz, Karolina; Sygut, Karolina Przybyłowska-; Majsterek, Ireneusz; Wozniacka, Anna; Narbutt, Joanna

    2016-01-01

    In recent decades, increases have been observed in the incidence of nonmelanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma. BCC is the most common neoplasm in Caucasian populations. Sonic hedgehog (Shh) pathway impairment plays a key role in BCC pathogenesis, and there is evidence that Shh pathway genetic variations may predispose to BCC development. We genotyped 22 single-nucleotide polymorphisms (SNPs) in 4 Shh pathway genes: SHH, GLI, SMO, and PTCH. The study group consisted of 142 BCC patients and 142 age-matched, sex-matched healthy subjects (controls). SNPs were assessed using the PCR-RFLP method. The genotype distribution for the polymorphisms in the rs104894049 331 A/T SHH, rs104894040 349 T/C SHH, and rs41303402 385 G/A SMO genes differed significantly between the BCC patients and the controls. The presence of CC genotype in the SHH rs104894040 349 T/C polymorphism was linked to the highest risk of BCC development (OR 87.9, p < 0.001). Other genotypes, such as the TT in SHH rs104894049 331 A/T and the GG in SMO rs41303402 385 G/A also statistically raised the risk of BCC, but these associations were weaker. Other investigated polymorphisms showed no statistical differences between patients and controls. The results obtained testify to the importance of the SHH and SMO gene polymorphisms in skin cancerogenesis. These results mainly underline the potential role of SHH3 rs104894040 349 T/C gene polymorphism in the development of skin basal cell carcinomas in patients of Polish origin.

  7. Tumour necrosis factor gene complex polymorphisms in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Ruse, Charlotte E; Hill, Maureen C; Tobin, Martin; Neale, Natalie; Connolly, Martin J; Parker, Stuart G; Wardlaw, Andrew J

    2007-02-01

    We aimed to examine the role of tumour necrosis factor gene complex polymorphisms in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that individuals possessing polymorphic variants associated with higher tumour necrosis factor (TNF) secretion would be more susceptible to and/or have more severe disease. Patients with COPD and population controls underwent detailed clinical phenotyping. Genotyping for the tumour necrosis factor-308 and the lymphotoxin alpha NcoI (LTalpha polymorphisms was carried out by 'blinded' laboratory staff. Three hundred and sixty one individuals (220 cases and 141 controls) were recruited. We showed an association between the LTalphaNcol polymorphism and forced vital capacity (FVC) in a population of older adults with and without COPD. The LTalphaNcol*2 allele was associated with poorer lung function, under a codominant model, with a fall in FVC (expressed as a percentage of its predicted value) of 3.7% for each copy of the LTalphaNcol*2 allele possessed (for FVC, regression coefficient (95% CI)=-3.73(-7.01 to -0.44), P=0.026; for FEV(1) regression coefficient=-3.56(-7.80 to 0.70), P=0.101. However, there was no difference in genotype distribution between the case and control populations. This study adds weight to the suggestion that the TNF gene complex is involved in physiological alterations (FVC) that may affect the development and severity of COPD. The absence of a significant association between the TNF gene-complex polymorphisms in this study does not rule out a modest effect of these polymorphisms on the risk of COPD, as much larger studies are needed to detect modest gene effects on binary disease endpoints.

  8. Contribution of protein Z gene single-nucleotide polymorphism to systemic lupus erythematosus in Egyptian patients.

    Science.gov (United States)

    Yousry, Sherif M; Shahin, Rasha M H; El Refai, Rasha M

    2016-09-01

    Protein Z has been reported to exert an important role in inhibiting coagulation. Polymorphisms in the protein Z gene (PROZ) may affect protein Z levels and thus play a role in thrombosis. This study aimed to investigate the prevalence and clinical significance of protein Z gene G79A polymorphism in Egyptian patients with systemic lupus erythematosus (SLE). We studied the distribution of the protein Z gene (rs17882561) (G79A) single-nucleotide polymorphism by PCR-restriction fragment length polymorphism in 100 Egyptian patients with SLE and 100 age, sex, and ethnically matched controls. There was no statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.103). But a statistically significant difference in the frequency of the alleles between SLE patients and controls was observed (P = 0.024). Also a significant association was detected between protein Z genotypes (and also A allele) and thrombosis, which is one of the manifestations of SLE (P = 0.004 and P = 0.001, respectively). Moreover, we observed a significant association between the protein Z AA and GA genotypes (and also A allele) and the presence of anticardiolipin antibodies (P = 0.016 and P = 0.004, respectively). The minor A allele of the G79A polymorphism in the protein Z gene might contribute to the genetic susceptibility of SLE in Egyptian patients. Also, an influence for this polymorphism on some of the disease manifestations has been elucidated, so protein Z G79A AG/AA may be a risk factor for thrombosis.

  9. Drd4 gene polymorphisms are associated with personality variation in a passerine bird.

    Science.gov (United States)

    Fidler, Andrew E; van Oers, Kees; Drent, Piet J; Kuhn, Sylvia; Mueller, Jakob C; Kempenaers, Bart

    2007-07-22

    Polymorphisms in several neurotransmitter-associated genes have been associated with variation in human personality traits. Among the more promising of such associations is that between the human dopamine receptor D4 gene (Drd4) variants and novelty-seeking behaviour. However, genetic epistasis, genotype-environment interactions and confounding environmental factors all act to obscure genotype-personality relationships. Such problems can be addressed by measuring personality under standardized conditions and by selection experiments, with both approaches only feasible with non-human animals. Looking for similar Drd4 genotype-personality associations in a free-living bird, the great tit (Parus major), we detected 73 polymorphisms (66 SNPs, 7 indels) in the P. major Drd4 orthologue. Two of the P. major Drd4 gene polymorphisms were investigated for evidence of association with novelty-seeking behaviour: a coding region synonymous single nucleotide polymorphism (SNP830) and a 15bp indel (ID15) located 5' to the putative transcription initiation site. Frequencies of the three Drd4 SNP830 genotypes, but not the ID15 genotypes, differed significantly between two P. major lines selected over four generations for divergent levels of 'early exploratory behaviour' (EEB). Strong corroborating evidence for the significance of this finding comes from the analysis of free-living, unselected birds where we found a significant association between SNP830 genotypes and differing mean EEB levels. These findings suggest that an association between Drd4 gene polymorphisms and animal personality variation predates the divergence of the avian and mammalian lineages. Furthermore, this work heralds the possibility of following microevolutionary changes in frequencies of behaviourally relevant Drd4 polymorphisms within populations where natural selection acts differentially on different personality types.

  10. New views on the selection acting on genetic polymorphism in central metabolic genes.

    Science.gov (United States)

    Eanes, Walter F

    2017-02-01

    Studies of the polymorphism of central metabolic genes as a source of fitness variation in natural populations date back to the discovery of allozymes in the 1960s. The unique features of these genes and their enzymes and our knowledge base greatly facilitates the systems-level study of this group. The expectation that pathway flux control is central to understanding the molecular evolution of genes is discussed, as well as studies that attempt to place gene-specific molecular evolution and polymorphism into a context of pathway and network architecture. There is an increasingly complex picture of the metabolic genes assuming additional roles beyond their textbook anabolic and catabolic reactions. In particular, this review emphasizes the potential role of these genes as part of the energy-sensing machinery. It is underscored that the concentrations of key cellular metabolites are the reflections of cellular energy status and nutritional input. These metabolites are the top-down signaling messengers that set signaling through signaling pathways that are involved in energy economy. I propose that the polymorphisms in central metabolic genes shift metabolite concentrations and in that fashion act as genetic modifiers of the energy-state coupling to the transcriptional networks that affect physiological trade-offs with significant fitness consequences. © 2016 New York Academy of Sciences.

  11. Cytosolic phospholipase A{sub 2} gene in human and rat: Chromosomal localization and polymorphic markers

    Energy Technology Data Exchange (ETDEWEB)

    Tay, A.; Simon, J.S.; Jacob, H.J. [Univ. of Toronto (Canada)] [and others

    1995-03-01

    The authors report the chromosomal localization and a simple sequence repeat (SSR) in the cytosolic phospholipase A{sub 2} (cPLA{sub 2}) gene in both human and rat. A (CA){sub 18} repeat in the promoter of the rat gene was determined to exhibit length polymorphism when analyzed using the polymerase chain reaction (PCR) in 19 different inbred rat strains. Genotyping for this marker in 234 F{sub 2} progeny of a SHRXBN intercross mapped the gene to rat chromosome 13. Using a PCR strategy, a fragment of the promoter for the human gene was isolated, and a (CA){sub 18} repeat was identified. Since this marker displayed a low heterozygosity index, they also identified a mononucleotide repeat in the promoter for cPLA{sub 2} that displayed a polymorphism information content value of 0.76. The human gene was mapped using fluorescence in situ hybridization (FISH) to chromosome 1q25. Of interest, the gene encoding the enzyme prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2), which acts on the arachidonic acid product of cPLA{sub 2}, was previously localized to this same chromosomal region, raising the possibility of coordinate regulation. Identification of intragenic markers may facilitate studies of polymorphic variants of these genes as candidates for disorders in which perturbations of the eicosanoid cascade may play a role. 20 refs., 3 figs., 2 tabs.

  12. Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development.

    Science.gov (United States)

    Theodoropoulos, George E; Saridakis, Vasilios; Karantanos, Theodoros; Michalopoulos, Nikolaos V; Zagouri, Flora; Kontogianni, Panagiota; Lymperi, Maria; Gazouli, Maria; Zografos, George C

    2012-08-01

    Toll-like receptor (TLR) activation may be an important event in tumor cell immune evasion. TLR2 and TLR4 gene polymorphisms have been related to increased susceptibility to cancer development in various organs. 261 patients and 480 health individuals were investigated for genotype and allelic frequencies of a 22-bp nucleotide deletion (-196 to -174del) in the promoter of TLR2 gene as well as two polymorphisms causing amino acid substitutions (Asp299Gly and Thr399Ile) in TLR4 gene. As far as (-196 to -174del) in TLR2 gene is concerned ins/del and del/del genotypes and del allele were significantly more frequent in breast cancer patients compared to healthy controls. Considering Asp299Gly replacement of TLR4 gene, Gly carriers (Asp/Gly & Gly/Gly genotype) and Gly allele were overrepresented among the breast cancer cases. The -174 to -196del of TLR2 gene and Asp299Gly of TLR4 gene polymorphisms may confer an increased susceptibility to breast cancer development.

  13. Polymorphism of the SCNN1g Gene and its Association with Eggshell Quality

    Directory of Open Access Journals (Sweden)

    Kheirkhah Z

    2017-06-01

    Full Text Available Eggshell quality is the main trait to assess egg quality. Marker assisted selection can be used to improve this trait. During eggshell formation, a mass of inorganic minerals is deposited. The Sodium Channel (SCNN1 gene family plays an essential role in cation transportation and SCNN1g is a member of this gene family. The objective of this study was to estimate the frequency of SCNN1g gene variants and to find its associations with eggshell quality in Hy-Line breed. 100 hens were randomly selected and their eggs and blood samples were collected. DNA was extracted and purified using the phenol-chloroform method and genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis. GLM procedure of SAS software was used to evaluate the association of SCNN1g gene polymorphism with egg weight, specific gravity, eggshell strength, eggshell weight, and eggshell thickness. Based on the polymorphism of SCNN1g gene, three genotypes were observed including AA, AG, and GG with frequencies of 0.26, 0.57, and 0.17, respectively. Genotype only had a significant effect on eggshell strength (P < 0.05. Other traits were not significantly influenced by genotypes of this gene. Therefore, introducing this gene in marker-assisted selection programs may improve eggshell strength of Hy-Line breed.

  14. Relationship Between Angiotensin-converting Enzyme Gene Polymorphism and QT Dispersion in Hemodialysis Patients.

    Science.gov (United States)

    Toraman, Aysun; Colak, Hulya; Tekce, Hikmet; Cam, Sirri; Kursat, Seyhun

    2017-05-01

    The angiotensin-converting enzyme (ACE) gene insertion or deletion in long-term hemodialysis patients may be associated with corrected QT interval prolongation, leading to fatal arrhythmias. The ACE D allele is known to increase the risk of malignant ventricular arrhythmias and is also associated with increased QT dispersion after myocardial infarction and hypertension. This study aimed to evaluate the relationship between ACE gene polymorphism and QT dispersion in hemodialysis patients. In 70 hemodialysis patients, electrocardiography was performed and QT dispersion was calculated. Corrected QT interval was calculated using Bazett Formula. The ACE gene polymorphism was determined by polymerase chain reaction. The mean age of the patients was 60 ± 12 years. The mean QT dispersion and corrected QT dispersion were 61.71 ± 21.99 and 73.18 ± 25.51, respectively. QT dispersion inversely correlated with serum calcium and potassium levels and positively correlated with ACE gene polymorphism and residual urine. Calcium level was the predictor factor for QT dispersion. The ACE genotype correlated with QT dispersion, corrected QT dispersion, hemoglobin, and residual urine, and inversely correlated with serum potassium. Corrected QT dispersion correlated with ACE gene polymorphism and residual urine. The DD genotype of ACE had significally greater QT dispersion and corrected QT dispersion than the II and ID genotypes. Our study showed that the most important parameter affecting corrected QT dispersion was ACE gene polymorphism on the background of D allelle. Patients carrying this allelle need special attention regarding optimal suppression of renin-angiotensin-aldosteron system activity.

  15. Thrombomodulin gene polymorphism and thrombomodulin expression in essential hypertension

    Institute of Scientific and Technical Information of China (English)

    WANG Yun-ying; BAO Zhen-min; ZHANG Qi-yi; DONG Hai; YU Xin-juan

    2006-01-01

    @@ Patients with hypertension have the characteristics of abnormalities of vessel wall,blood constituents and blood flow. These abnormalities may confer a prothrombotic or hypercoagulable state and are related to the damage of target organs and long-term prognosis. Soluble thrombomodulin (sTM) as abnormalities of levels of specific plasma markers of endothelial damage or dysfunction may relate with the complications of hypertension and the determination of blood pressure itself. TM plays a critical role as a co-factor in the protein C pathway, 1 which is important in regulating coagulation as well as inflammation. Thus we hypothesized that the -33G>A polymorphism alter thrombomodulin expression and/or impair anticoagulant function, which can predispose to the damage of the target organs during the progress of hypertension. Then, we investigated a possible association of sTM, TM on monocytes and the -33G>A polymorphism with essential hypertension and cardiovascular disease (CVD) in the Chinese Han ethnic population.

  16. Single Nucleotide Polymorphism Analysis of Protamine Genes in Infertile Men

    Directory of Open Access Journals (Sweden)

    Ahamad Salamian

    2008-01-01

    Full Text Available Background: Single nucleotide polymorphism (SNPs are considered as one of the underlyingcauses of male infertility. Proper sperm chromatin packaging which involves replacement ofhistones with protamines has profound effect on male fertility. Over 20 SNPs have been reportedfor the protamine 1 and 2.Materials and Methods: The aim of this study was to evaluate the frequency of two previouslyreported SNPs using polymerase chain reaction (PCR-restriction fragment length polymorphism(RFLP approach in 35, 96 and 177 normal, oligozoospermic and azoospermic individuals. TheseSNPs are: 1. A base pair substitution (G at position 197 instead of T in protamine type 1 Openreading frame (ORF including untranslated region, which causes an Arg residue change to Serresidue in a highly conserved region. 2. cytidine nucleotide change to thymidine in position of 248of protamine type 2 ORF which caused a nonsense point mutation.Results: The two mentioned SNPs were not present in the studied population, thus concluding thatthese SNPs can not serves as molecular markers for male infertility diagnosis.Conclusion: The results of our study reveal that in a selected Iranian population, the SNP G197Tand C248T are completely absent and are not associated with male infertility and therefore theseSNPs may not represent a molecular marker for genetic diagnosis of male infertility.

  17. Relation between the hypertriglyceridemic waist and the gene polymorphism of PPARs

    Institute of Scientific and Technical Information of China (English)

    朱秋荣

    2013-01-01

    Objective To analyze the correlation between the 3subtypes of PPAR genes (PPARα,PPARβ,and PPARγ) and the hypertriglyceridemic waist (HTGW) ,and to study whether there is an interaction in the 10 single nucleotide polymorphisms (SNPs) of the above 3 subtypes in causing HTGW.Methods Eight hundred and

  18. The Relationship between Interleukin-6 -174 G/C Gene Polymorphism and Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Tayebeh Sanchooli

    2012-03-01

    Full Text Available Background: Chronic periodontitis is an inflammatory disease that causes rapid destruction of the tissues supporting the teeth. Genetic and environmental factors are involved in its occurrence. It has been suggested that IL-6 promoter gene polymorphism could affect the severity of chronic periodontitis. This study has examined the relationship between IL-6 (-174G/C gene polymorphism and chronic periodontitis.Materials and Methods: In this case-control study, 100 patients with chronic periodontitis and 100 healthy individuals referring to the clinic of Zahedan Dental School were evaluated. Two ml of peripheral blood was taken from these people. After DNA extraction through salting out method, IL-6 gene polymorphism was determined through T-ARMS-PCR technique using specific primers. The data were analyzed by chi-square test and p<0/05was considered significant.Results: The frequency of genotypes CC, GC, GG was respectively 61%, 35% and 4% in patients and respectively 67%, 31% and 2% in the control group. The frequency of G and C alleles was respectively 78.5% and 21.5% in the patient group, and respectively 82.5% and 17.5% in control group. No statistically significant difference was observed between the two groups in frequency of genotypes and alleles.Conclusion: This study showed no correlation between IL-6-174 G/C gene polymorphism and chronic periodontitis.

  19. DNA polymorphism of HLA class II genes in pauciarticular juvenile rheumatoid arthritis

    DEFF Research Database (Denmark)

    Morling, N; Friis, J; Fugger, L;

    1991-01-01

    We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DPB in 54 patients with pauciarticular juvenile rheumatoid arthritis (PJRA) and in healthy Danes. The frequencies of DNA fragments a...

  20. The CXCR2 Gene Polymorphism Is Associated with Stroke in Patients with Essential Hypertension

    Directory of Open Access Journals (Sweden)

    Yanina R. Timasheva

    2015-10-01

    Full Text Available Hypertension is the major risk factor for stroke, and genetic factors contribute to its development. Inflammation has been hypothesized to be the key link between blood pressure elevation and stroke. We performed an analysis of the association between inflammatory mediator gene polymorphisms and the incidence of stroke in patients with essential hypertension (EH. The study group consisted of 625 individuals (296 patients with noncomplicated EH, 71 hypertensive patients with ischemic stroke, and 258 control subjects. Both patients and controls were ethnic Tatars originating from the Republic of Bashkortostan (Russian Federation. The analysis has shown that the risk of ischemic stroke was associated with the CXCR2 rs1126579 polymorphism. Our results indicate that among patients with EH, the heterozygous genotype carriers had a higher risk of stroke (OR = 1.72, 95% CI 1.01-2.92, whereas the CXCR2*C/C genotype was protective against stroke (OR = 0.32, 95% CI 0.12-0.83. As shown by the gene-gene interaction analysis, the CXCR2 rs1126579 polymorphism was also present in all genotype/allele combinations associated with the risk of stroke. Genetic patterns associated with stroke also included polymorphisms in the CCL2, CCL18, CX3CR1, CCR5, and CXCL8(IL8 genes, although no association between these loci and stroke was detected by individual analysis.

  1. Association between polymorphisms in segregation genes BUB1B and TTK and gastric cancer risk

    Directory of Open Access Journals (Sweden)

    Hudler Petra

    2016-09-01

    Full Text Available Malignant transformation of normal gastric cells is a complex and multistep process, resulting in development of heterogeneous tumours. Susceptible genetic background, accumulation of genetic changes, and environmental factors play an important role in gastric carcinogenesis. Single nucleotide polymorphisms (SNPs in mitotic segregation genes could be responsible for inducing the slow process of accumulation of genetic changes, leading to genome instability.

  2. Polymorphisms in human DNA repair genes and head and neck squamous cell carcinoma

    Indian Academy of Sciences (India)

    Rim Khlifi; Ahmed Rebai; Amel Hamza-Chaffai

    2012-12-01

    Genetic polymorphisms in some DNA repair proteins are associated with a number of malignant transformations like head and neck squamous cell carcinoma (HNSCC). Xeroderma pigmentosum group D (XPD) and X-ray repair cross-complementing proteins 1 (XRCC1) and 3 (XRCC3) genes are involved in DNA repair and were found to be associated with HNSCC in numerous studies. To establish our overall understanding of possible relationships between DNA repair gene polymorphisms and development of HNSCC, we surveyed the literature on epidemiological studies that assessed potential associations with HNSCC risk in terms of gene–environment interactions, genotype-induced functional defects in enzyme activity and/or protein expression, and the influence of ethnic origin on these associations.We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of HNSCC when DNA repair capacity is reduced.

  3. MY09B gene polymorphisms are associated with autoimmune diseases in Spanish population

    NARCIS (Netherlands)

    Sanchez, Elena; Alizadeh, Behrooz Z.; Valdigem, Gustavo; Ortego-Centeno, Norberto; Jimenez-Alonso, Juan; de Ramon, Enrique; Garcia, Antonio; Lopez-Nevot, Miguel A.; Wijmenga, Cisca; Martin, Javier; Koeleman, Bobby P. C.

    2007-01-01

    The aim of the study was to test MYO9B gene polymorphisms for association with three autoimmune diseases, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and celiac disease (CD), in a Spanish population. We analyzed three SNPs (rs2305767, rs1457092, and rs2305764) in a case-control co

  4. Clinical Efficacy of Fluvoxamine and Functional Polymorphism in a Serotonin Transporter Gene on Childhood Autism

    Science.gov (United States)

    Sugie, Yoko; Sugie, Hideo; Fukuda,Tokiko; Ito, Masataka; Sasada, Yumiko; Nakabayashi, Mutsumi; Fukashiro, Kazunobu; Ohzeki, Takehiko

    2005-01-01

    We studied the correlation between response to fluvoxamine and serotonin transporter gene promoter region polymorphism (5-HTTLPR). Eighteen children with autistic disorder completed a 12-week double-blind, placebo-controlled, randomized crossover study of fluvoxamine. Behavioral assessments were obtained before and at 12 weeks of treatment.…

  5. Phosphodiesterase 4 D Gene Polymorphism in Relation to Intracranial and Extracranial Atherosclerosis in Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Jayantee Kalita

    2011-01-01

    Full Text Available In ischemic stroke, extracranial MR angiography (ECMRA is more frequently abnormal in Caucasians and intracranial (ICMRA in Asians which may have a genetic basis. We report phosphodiesterase (PDE4D gene polymorphism and its correlation with MRA findings in patients with ischemic stroke.

  6. Association of vitamin D receptor gene polymorphism with the urine calcium level in nephrolithiasis patients.

    Science.gov (United States)

    Zhou, Tian-Biao; Jiang, Zong-Pei; Huang, Miao-Fang; Zhang, Rui

    2015-04-01

    Association of vitamin D receptor (VDR) gene polymorphism with the urine calcium level in nephrolithiasis patients from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and urine calcium level in nephrolithiasis patients using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 April 2014, and eligible investigations were included and synthesized using meta-analysis method. Four reports were recruited into this meta-analysis for the association of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism with urine calcium level in nephrolithiasis patients. In this meta-analysis, VDR BsmI B allele and BB genotype, Fok1 f allele and ff genotype, TaqI, and ApaI gene polymorphism were not associated with urine calcium level in nephrolithiasis patients. However, the BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. In conclusion, VDR BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. However, more studies should be conducted to confirm it.

  7. LAPTM4B Gene Expression And Polymorphism As Diagnostic Markers Of Breast Cancer In Egyptian Patients

    Directory of Open Access Journals (Sweden)

    Shaker Olfat

    2015-10-01

    Full Text Available Background: The aim of this study was to investigate the association between LAPTM4B gene polymorphism and the risk of breast cancer among Egyptian female patients. Also, measurement was done of its serum level to evaluate its significance as a diagnostic marker for breast cancer.

  8. Polymorphisms of the OXTR gene explain why sales professionals love to help customers

    NARCIS (Netherlands)

    W.J.M.I. Verbeke (Willem); R.P. Bagozzi (Richard); W.E. van den Berg (Wouter); A. Lemmens (Aurélie)

    2013-01-01

    textabstractPolymorphisms of the OXTR gene affect people's social interaction styles in various social encounters: carriers of the OXTR GG, compared to the OXTR AA/AG in general, are more motivated to interact socially and detect social salience. We focus on sales professionals operating in knowledg

  9. A systematic review of meta-analyses on gene polymorphisms and gastric cancer risk

    NARCIS (Netherlands)

    F. Gianfagna (Francesco); E. de Feo (Emma); C.M. van Duijn (Cock); G. Ricciardi (Gualtiero); S. Boccia (Stefania)

    2008-01-01

    textabstractBackground: Individual variations in gastric cancer risk have been associated in the last decade with specific variant alleles of different genes that are present in a significant proportion of the population. Polymorphisms may modify the effects of environmental exposures, and these

  10. The Association between Infants' Self-Regulatory Behavior and MAOA Gene Polymorphism

    Science.gov (United States)

    Zhang, Minghao; Chen, Xinyin; Way, Niobe; Yoshikawa, Hirokazu; Deng, Huihua; Ke, Xiaoyan; Yu, Weiwei; Chen, Ping; He, Chuan; Chi, Xia; Lu, Zuhong

    2011-01-01

    Self-regulatory behavior in early childhood is an important characteristic that has considerable implications for the development of adaptive and maladaptive functioning. The present study investigated the relations between a functional polymorphism in the upstream region of monoamine oxidase A gene (MAOA) and self-regulatory behavior in a sample…

  11. A single nucleotide polymorphism of porcine MX2 gene provides antiviral activity against vesicular stomatitis virus.

    Science.gov (United States)

    Sasaki, Keisuke; Tungtrakoolsub, Pullop; Morozumi, Takeya; Uenishi, Hirohide; Kawahara, Manabu; Watanabe, Tomomasa

    2014-01-01

    The objective was to determine if single nucleotide polymorphisms (SNPs) in porcine MX2 gene affect its antiviral potential. MX proteins are known to suppress the multiplication of several viruses, including influenza virus and vesicular stomatitis virus (VSV). In domestic animals possessing highly polymorphic genome, our previous research indicated that a specific SNP in chicken Mx gene was responsible for its antiviral function. However, there still has been no information about SNPs in porcine MX2 gene. In this study, we first conducted polymorphism analysis in 17 pigs of MX2 gene derived from seven breeds. Consequently, a total of 30 SNPs, of which 11 were deduced to cause amino acid variations, were detected, suggesting that the porcine MX2 is very polymorphic. Next, we classified MX2 into eight alleles (A1-A8) and subsequently carried out infectious experiments with recombinant VSVΔG*-G to each allele. In A1-A5 and A8, position 514 amino acid (514 aa) of MX2 was glycine (Gly), which did not inhibit VSV multiplication, whereas in A6 and A7, 514 aa was arginine (Arg), which exhibited the antiviral ability against VSV. These results demonstrate that a SNP at 514 aa (Gly-Arg) of porcine MX2 plays a pivotal role in the antiviral activity as well as that at 631 aa of chicken Mx.

  12. Correlation between endometriosis combined with infertility and STAT3 gene polymorphisms

    Institute of Scientific and Technical Information of China (English)

    Juan Hu; Feng Ye

    2016-01-01

    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.

  13. Association between Rho-kinase (ROCK2) gene polymorphisms and Behçet's disease.

    Science.gov (United States)

    Oguz, Elif; Alasehirli, Belgin; Pehlivan, Yavuz; Onat, Ahmet Mesut; Oztuzcu, Serdar; Ozkara, Esma; Kisacik, Bünyamin; Camci, Celaletdin; Demiryürek, Abdullah T

    2012-12-01

    Behçet's disease (BD) is a multi-systemic vasculitis. The aim of this study was to investigate the association between Rho-kinase (ROCK2) gene polymorphisms and patients with BD in a Turkish population. A total of 194 BD patients and 276 healthy controls with similar age and sex were included to this study. Polymorphisms were analyzed in genomic DNA using a BioMark 96.96 dynamic array system. mRNA from blood samples was extracted, and real-time polymerase chain reaction was performed for ROCK2 gene expression. There were marked changes in both genotype (TT, 41.8%; TA, 30.3%) and allele (T, 57%; A, 43%) frequencies for the rs35768389 (Asp601Val) polymorphism in patients compared with controls (TT, 64.6%; TA, 9.4%, P ROCK2 e