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, OR = 1.652 with 95% CI 1.086 2.513, P = 0.019 under a recessive model, and OR = 1.521 with 95% CI 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.
Wang
Fang
F
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
Han
Xue-yao
XY
Ren
Qian
Q
Zhang
Xiu-ying
XY
Han
Ling-chuan
LC
Luo
Ying-ying
YY
Zhou
Xiang-hai
XH
Ji
Li-nong
LN
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D051557:Hepatocyte Nuclear Factor 4; D047495:PPAR gamma; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C496592:HNF4A protein, human