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GA Genotype (ga + genotype)
Selected AbstractsPeroxisome proliferator-activated receptor-, co-activator-1, (PGC-1,) gene polymorphisms and their relationship to Type 2 diabetes in Asian IndiansDIABETIC MEDICINE, Issue 11 2005K. S. Vimaleswaran Abstract Aims The objective of the present investigation was to examine the relationship of three polymorphisms, Thr394Thr, Gly482Ser and +A2962G, of the peroxisome proliferator activated receptor-, co-activator-1 alpha (PGC-1,) gene with Type 2 diabetes in Asian Indians. Methods The study group comprised 515 Type 2 diabetic and 882 normal glucose tolerant subjects chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The three polymorphisms were genotyped using polymerase chain reaction,restriction fragment length polymorphism (PCR,RFLP). Haplotype frequencies were estimated using an expectation,maximization (EM) algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. Results The three polymorphisms studied were not in linkage disequilibrium. With respect to the Thr394Thr polymorphism, 20% of the Type 2 diabetic patients (103/515) had the GA genotype compared with 12% of the normal glucose tolerance (NGT) subjects (108/882) (P = 0.0004). The frequency of the A allele was also higher in Type 2 diabetic subjects (0.11) compared with NGT subjects (0.07) (P = 0.002). Regression analysis revealed the odds ratio for Type 2 diabetes for the susceptible genotype (XA) to be 1.683 (95% confidence intervals: 1.264,2.241, P = 0.0004). Age adjusted glycated haemoglobin (P = 0.003), serum cholesterol (P = 0.001) and low-density lipoprotein (LDL) cholesterol (P = 0.001) levels and systolic blood pressure (P = 0.001) were higher in the NGT subjects with the XA genotype compared with GG genotype. There were no differences in genotype or allelic distribution between the Type 2 diabetic and NGT subjects with respect to the Gly482Ser and +A2962G polymorphisms. Conclusions The A allele of Thr394Thr (G , A) polymorphism of the PGC-1 gene is associated with Type 2 diabetes in Asian Indian subjects and the XA genotype confers 1.6 times higher risk for Type 2 diabetes compared with the GG genotype in this population. [source] ,93G,A polymorphism of hMLH1 and risk of primary lung cancerINTERNATIONAL JOURNAL OF CANCER, Issue 4 2004Sun Ha Park Abstract Polymorphisms in DNA repair genes may be associated with differences in the repair capacity of DNA damage and may thereby influence an individual's susceptibility to smoking-related cancer. We investigated the association between the ,93G,A polymorphism in the hMLH1 gene and the risk of lung cancer in a Korean population. The hMLH1 ,93G,A polymorphism was typed in 372 lung cancer patients and 371 healthy controls that were frequency-matched for age and sex. There was no significant association between the hMLH1 ,93G,A genotype and the risk for adenocarcinoma or small cell carcinoma. However, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma compared with both the GG genotype (adjusted OR = 2.02; 95% CI = 1.15,3.55; p = 0.014) and the combined GG and GA genotype (adjusted OR = 1.83; 95% CI = 1.24,2.71; p = 0.003). When the subjects were stratified by smoking exposure, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma in lighter smokers (, 39 pack-years; adjusted OR = 1.95; 95% CI = 1.03,3.66; p = 0.039) compared with the combined GG and GA genotype, whereas there was no significant association in heavier smokers (> 39 pack-years; adjusted OR = 1.47; 95% CI = 0.82,2.61). These results suggest that the hMLH1 ,93G,A polymorphism could be used as a marker of genetic susceptibility to squamous cell carcinoma of the lung. © 2004 Wiley-Liss, Inc. [source] The Tumor Necrosis Factor Alpha ,308G>A Polymorphism Is Associated with Dementia in the Oldest OldJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2004Helle Bruunsgaard MD Objectives: To test the hypothesis that the tumor necrosis factor (TNF) ,308 G>A promoter gene polymorphism is a risk factor in age-related dementia and longevity. Design: A cross-sectional and a longitudinal study. Setting: A population-based sample of Danish centenarians. Participants: One hundred-year-old Danes (n=122) from "The Longitudinal Study of Danish Centenarians." Octogenarians (n=174) and healthy volunteers aged 18 to 30 (n=47) served as reference groups. Methods: Whether the distribution of TNF ,308 GG/GA/AA genotypes were different in centenarians than in younger age groups was investigated (Fischer exact test). Furthermore, whether the TNF ,308 G>A polymorphism was associated with the prevalence of dementia (logistic regression analysis), the plasma level of TNF-, (analysis of variance), and mortality in the following 5 years (Cox regression analysis) within the cohort of centenarians was tested. Results: The distribution of TNF ,308 genotypes was not different across the three different age groups, but the GA genotype was associated with decreased prevalence of dementia in centenarians. The few centenarians with AA carrier status had higher mortality risk and tended to show higher plasma levels of TNF-,, but the significance was questionable due to a low number of subjects with this genotype. Conclusion: It is possible that the TNF ,308 A allele is maintained during aging because subjects who are heterozygous for this polymorphism possess the optimal inflammatory response with regard to protection against age-related neurodegeneration. [source] Low Expression Myeloperoxidase Genotype Negatively Associated with Helicobacter pylori InfectionCANCER SCIENCE, Issue 5 2001Nobuyuki Hamajima Our previous study revealed that a polymorphism of the interleukin (IL) 1B gene, encoding the pro-inflammatory cytokine IL-l,, influenced the prevalence of persistent Helicobacter pylori (HP) infection. In this paper, a polymorphism of another inflammation-related enzyme, myeloperoxidase (MPO), was examined with respect to association with the HP infection. The polymorphism is due to a G-to-A transition at -463 in the promoter region of MPO. The G allele is the wild type with normal expression, while the A allele is a low expression allele. The subjects were 241 non-cancer outpatients (118 males and 123 females) aged 39 to 69 who participated in an HP eradication program at Aichi Cancer Center Hospital. High-molecular weight Campylobacter-Associated-Protein (HM-CAP) ELISA (Enteric Products Ins., Westbury, NY) was used for the identification of HP -infected participants. The frequency was 79.7% (192/241) for the GG genotype, 19.5% (47/241) for the GA genotype, and 0.8% (2/241) for the AA genotype. The sex-age-adjusted odds ratio (OR) relative to GG was 0.69 (95% confidence interval (CI), 0.35,1.35) for individuals with the A allele, but among male participants the OR was 0.31 (0.11,0.84). Subgroup analysis revealed significantly reduced ORs with the GA/AA genotypes for current smokers (0.19, 0.04,0.96), and for those who were occasional/no milk drinkers (0.25, 0.09,0.72). These findings are consistent with the results for IL-1B in our earlier study, suggesting that inflammatory responses in the gastric mucosa may influence persistent HP infection, and that smoking and milk intake may be effect -modifiers. [source] The apo A-I gene promoter region polymorphism determines the severity of hyperlipidemia after heart transplantationCLINICAL TRANSPLANTATION, Issue 1 2003Angel González-Amieva Abstract: Background: To study whether the Apolipoprotein A-I (apo A-I) promoter region gene polymorphism produces changes in the lipid profile of heart transplant recipients. Methods: One hundred and three heart transplant recipients (93 men and 10 women, with a mean age of 47 ± 13 yr) receiving triple immunosuppressive therapy were submitted to a genetic study of the apo A-I gene promoter region. Anthropometric and analytical data, including lipid profile, arterial blood pressure, were collected prior to transplantation and 3, 6, 12, and 24 months after transplantation. Results: Sixty-three subjects had the GG genotype and 40 the GA genotype. Carriers of the GA genotype had higher triglyceride levels at 6 months and 2 yr (2.50 ± 1.20 versus 1.93 ± 0.98 mmol/L and 2.46 ± 1.58 versus 1.60 ± 0.68 mmol/L, respectively, p < 0.001), and a greater rise in LDL-cholesterol at 1 yr than the GG subjects (4.57 ± 1.16 versus 4.16 ± 1.18 mmol/L, p < 0.05). Multiple regression analyses showed that genetic variants at the apo A-I promoter region are responsible for 11% of the variability in triglyceride levels at 6 months (p = 0.005). Conclusions: The GA genotype of the apo A-I promoter region produces a greater rise in plasma triglyceride and LDL-cholesterol levels in heart transplant patients. [source] | ||||||||||