首页|期刊导航|中华医学杂志（英文版）|Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population
中华医学杂志（英文版）2009，Vol.122Issue(20)：2477-2482,6.DOI:10.3760/cma.j.issn.0366-6999.2009.20.015
Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population
Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population
摘要
Abstract
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(R) 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% Cl 1.117 1.755, P=0.004 under an additive model, OR=-1.652 with 95% Cl 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.关键词
type 2 diabetes/ KCNJ11/ ABCC8/ PPARG/ HNF4AKey words
type 2 diabetes/ KCNJ11/ ABCC8/ PPARG/ HNF4A分类
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WANG Fang,HAN Xue-yao,REN Qian,ZHANG Xiu-ying,HAN Ling-chuan,LUO Ying-ying,ZHOU Xiang-hai,JI Li-nong..Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population[J].中华医学杂志（英文版）,2009,122(20):2477-2482,6.基金项目
This study was supported by National High Technology Research and Development Program ("863" program, No. 2006AA02A409)and National Basic Research Program of China ("973" program, No. 2006CB503900). （"863" program, No. 2006AA02A409）
