Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population

Background KCNJ11, ABCC8, PPARG, and HNF4A have been found to be associated with type 2 diabetes in populations with different genetic backgrounds. The aim of this study was to test, in a Chinese Han population from Beijing, whether the genetic variants in these four genes were associated with genetic predisposition to type 2 diabetes. Methods We studied the association of four representative SNPs in KCNJ11, ABCC8, PPARG, and HNF4A by genotyping them using ABI SNaPshot Multiplex System in 400 unrelated type 2 diabetic patients and 400 unrelated normoglycaemic subjects. Results rs5219（E23K） in KCNJ11 was associated with genetic susceptibility to type 2 diabetes （OR=1.400 with 95% CI 1.117 1.755, P=0.004 under an additive model, 0R=1.652 with 95% CI 1.086 2.513, P=0.019 under a recessive model, and OR=1.521 with 95% Cl 1.089 2.123, P=0.014 under a dominant model） after adjusting for sex and body mass index （BMI）. We did not find evidence of association for ABCC8 rs1799854, PPARG rs1801282 （Pro12Ala） and HNF4A rs2144908. Genotype-phenotype correlation analysis revealed that rs1799854 in ABCC8 was associated with 2-hour postprandial insulin secretion （P=0.005） after adjusting for sex, age and BMI. Although no interactions between the four variants on the risk of type 2 diabetes were detected, the multiplicative interaction between PPARG Pro12Ala and HNF4A rs2144908 was found to be associated with 2-hour postprandial insulin （P=-0.004 under an additive model for rs2144908; and P=0.001 under a dominant model for rs2144908） after adjusting for age, sex and BMI, assuming a dominant model for PPARG Pro12Ala. Conclusions Our study replicated the association of rs5219 in KCNJ11 with type 2 diabetes in Chinese Han population in Beijing. And we also observed that ABCC8 as well as the interaction between PPARG and HNF4A may contribute to post-challenge insulin secretion.