Association Of Polymorphisms In IL6R, APM1 And KCNQ1 With Type 2 Diabetes In Han Chinese In Hubei

Objective:Type 2 diabetes(T2DM) is a complex disease which is determined by both genetic and environmental factors.Because of the genetic heterogeneity, conclusions about the association between T2DM and candidate genes were inconsistent across different countries or populations.Objective of this study is to test the association between IL6R D358A(rs8192284),APM1 SNP45(rs13061862) and KCNQ1 rs2237892 polymorphisms and T2DM in Han Chinese in Hubei.Methods:Case-control design was used in this study.The IL6R D358A and APM1 SNP45 polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphisms method,and the KCNQ1 rs2237892 polymorphism was genotyped by fluorescence quantitative polymerase chain reaction analysis in 981 Han Chinese in Hubei province.The Chi-square test,logistic regression test and Meta analysis were used to investigate the relationship between polymorphisms of IL6R, APM1 and KCNQ1 and T2DM.Results:1.Genotypic and allelic frequencies of IL6R D358A,APM1 SNP45 and KCNQ1 rs2237892 polymorphisms were in Hardy-Weinberg equilibrium.2.Frequencies of the IL6R D358A CC genotype and C allele for T2DM patients were significantly lower than those for controls(CC:13.4%vs.20.0%,P=0.006;C: 36.0%vs.41.4%,P=0.016).The allele C reduced the risk of T2DM(OR=0.62,P=0.006). Results of subgroup analysis showed the interaction between IL6R D358A and sex/BMI. Logistic regression analysis indicated that the CC genotype was significantly associated with the lower risk of T2DM(unadjusted:OR=0.603,95.%CI=0.415～0.875,P=0.008; adjusted:OR=0.621,95%CI=0.424～0.910,P=0.014).Our results suggested that IL6R D358A was associated with T2DM in Han Chinese in Hubei,and the CC genotype may serve as a genetic preventive factor of T2DM,which was supported by the result of Meta-analysis(P=0.002,OR=0.65,95%CI=0.50～0.86).3.The frequencies of the APM1 SNP45 GG genotype for T2DM patients were significantly higher than those for controls(GG:11.1%vs.6.3%,P=0.015).But allelic frequencies showed no difference between T2DM and controls.Logistic regression analysis showed that the GG genotype was significantly associated with T2DM (unadjusted:OR=1.808,95%CI=1.089～2.999,P=0.022;adjusted:OR=1.982,95%CI= 1.211～3.018,P=0.034).These results suggested that APM1 was a susceptibility gene for T2DM in Han Chinese in Hubei,and the GG genotype may serve as a genetic risk factor of T2DM.Meta-analysis of studies in all Chinese subjects suggested that GG genotype was significantly associated with T2DM(P＜0.00001,OR=2.45,95%CI=1.86～3.24).4.No differences in genotypic and allelic frequencies of the KCNQ1 rs2237892 polymorphism were detected between T2DM and controls(genotype:P=0.562;allele: P=0.295).Logistic regression analysis also indicated that the KCNQ1 rs2237892 polymorphism was not associated with T2DM.But Meta-analysis showed KCNQ1 rs2237892 was significantly associated with T2DM,and CC genotype may serve as a genetic risk factor of T2DM(P＜0.001,OR=1.25,95%CI=1.21～1.29).Conclusions:1.IL6R D358A is associated with T2DM in Han Chinese in Hubei,and the CC genotype may serve as a genetic preventive factor of T2DM.2.APM1 SNP45 is a susceptibility gene for T2DM in Han Chinese in Hubei,and the GG genotype may serve as a genetic risk factor of T2DM.3.KCNQ1 rs2237892 polymorphism is not associated with T2DM in this study.