|Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population|
|Wang Fang; Han Xue-yao; Ren Qian; Zhang Xiu-ying; Han Ling-chuan; Luo Ying-ying; Zhou Xiang-hai; Ji Li-nong|
|关键词||type 2 diabetes KCNJ11 ABCC8 PPARG HNF4A|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
|关键词[WOS]||GENOME-WIDE ASSOCIATION ; FACTOR-4-ALPHA P2 PROMOTER ; BETA-CELL FUNCTION ; SULFONYLUREA RECEPTOR ; PRO12ALA POLYMORPHISM ; INSULIN SENSITIVITY ; JAPANESE POPULATION ; DECREASED RISK ; CHROMOSOME 20Q ; RESISTANCE|
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 KG-NJ11 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, PL=0.019 under a recessive model, and OR=1.521 with 95% Cl 1.089 2.123, PL=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. Chin Med J 2009;122(20):2477-2482
|项目编号||2006AA02A409 ; 2006CB503900|
|资助机构||National High Technology Research and Development Program ; National Basic Research Program of China|
|作者单位||Peking Univ, Peoples Hosp, Dept Endocrinol & Metab, Beijing 100044, Peoples R China|
|Wang Fang,Han Xue-yao,Ren Qian,et al. Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population[J]. CHINESE MEDICAL JOURNAL,2009,122(20):2477-2482.|
|APA||Wang Fang.,Han Xue-yao.,Ren Qian.,Zhang Xiu-ying.,Han Ling-chuan.,...&Ji Li-nong.(2009).Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population.CHINESE MEDICAL JOURNAL,122(20),2477-2482.|
|MLA||Wang Fang,et al."Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population".CHINESE MEDICAL JOURNAL 122.20(2009):2477-2482.|