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)
Chinese Medical Journal
;
(24): 2477-2482, 2009.
Article
in English
| WPRIM
| ID: wpr-266043
ABSTRACT
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Receptors, Drug
/
Body Mass Index
/
ATP-Binding Cassette Transporters
/
Genetic Predisposition to Disease
/
Polymorphism, Single Nucleotide
/
Potassium Channels, Inwardly Rectifying
/
PPAR gamma
/
Diabetes Mellitus, Type 2
/
Hepatocyte Nuclear Factor 4
/
Sulfonylurea Receptors
Type of study:
Prognostic study
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
English
Journal:
Chinese Medical Journal
Year:
2009
Type:
Article
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