Association Analyses Of KCNJ11 And SUR1 Gene Polymorphisms With Type 2 Diabetes In Han Chinese In Hubei

Objective: Type 2 diabetes (T2DM) is a common metabolic disease with complex genetic components. A number of susceptibility loci and candidate genes for T2DM have been reported, but the results are inconsistent among different populations because of the genetic heterogeneity. Objective of this study is to test the association between KCNJ11 E23K and SUR1 16-3t/c polymorphisms and T2DM in Han Chinese in Hubei.Methods: Both sib-pairs (within-family control) and random case-control designs were used. The KCNJ11 gene E23K polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 400 subjects. The 16-3t/c polymorphism in the SUR1 gene was analyzed using PCR-RFLP in 464 case-control subjects. Height, weight, waist circumference, hip circumference, blood pressure and fasting blood glucose were measured, and the body mass index (BMI) and waist to hip ratio (WHR) were calculated in all subjects. All subjects were divided into three groups: all T2DM patients and controls, sib-pairs of patients and controls, T2DM patients and unrelated controls. Independent-sample t test was used to compare means between two groups, while paired-sample t test was used for the comparison of sib-pairs means. ANOVA was employed to compare the differences of clinical characteristics between genotypes. Chi-square test was employed to test the differences of genotypic and allelic frequencies between cases and controls. Association analyses were done by logistic regression. All statistical analyses were performed with the software of SPSS 11.5 for windows.Results: (1) There were significant differences in the genotypic and allelic frequencies of the KCNJ11 gene E23K polymorphism between cases and controls in random case-control designs and all subjects studied (P< 0.05 or P < 0.01) . Logistic regression analysis indicated that KCNJ11 gene E23K polymorphism was significantly related to T2DM in random case-control design, and KK genotype is associated with T2DM in all subjects studied.(2) No differences of the genotypic and allelic frequencies of the SUR1 gene 16-3t/c polymorphism were observed between cases and controls in both of study designs. In stratified analysis on the basis of sex, age and BMI level, there were also no significant differences. After adjusting sex, age, hypertension and obesity, there were still no significant differences. However, the result of univariate analysis showed that there were significant differences in waist circumference and hip circumference among three genotypes of SUR1 gene in cases and all subjects. In addition, significant difference in BMI was observed, the cases being obviously higher than the controls. Logistic regression analysis showed that BMI was one of the independent risk factors for T2DM.Conclusion: T2DM is not associated with 16-3t/c polymorphism of the SUR1 gene. The KCNJ11 gene E23K polymorphism is associated with T2DM and may be a susceptibility locus for T2DM in Han Chinese in Hubei.