Association of the PPARG Pro12Ala polymorphism with type 2 diabetes and incident coronary heart disease in a Hong Kong Chinese population

Abstract

Aims: We examined the risk association between single nucleotide polymorphisms (SNPs) in eleven candidate genes with type 2 diabetes (T2D). T2D-associated polymorphisms were also examined for prediction of incident CHD.

Methods: 113 tagging SNPs were genotyped in stage 1 (467 T2D cases, 290 controls), and 15 SNPs were analyzed in the final cohort (1462 T2D cases, 600 controls). Three T2D-associated SNPs were further tested for prediction of CHD within a subset of 1417 T2D cases free of CHD at enrolment.

Results: In the case-control analysis, PPARG rs1801282 (Pro12Ala) (OR=1.48 (1.02-2.16)), ADIPOQ rs1063539 (OR=1.17 (1.01-1.35)), and HNF4A rs1884614 (OR=1.16 (1.00-1.32) were associated with T2D (P(allelic)<0.05). Joint analysis of rs1801282-C, rs1063539-G, and rs1884614-T risk alleles showed an additive dosage effect (P for trend=0.001). Moreover, carriers with two PPARG rs1801282-C risk alleles were associated with an increased risk of incident CHD (HR=4.38 (1.03-18.57), P=0.045) in T2D patients in the prospective analysis.

Conclusions: Genetic variants of PPARG, ADIPOQ and HNF4A were individually and jointly associated with T2D in Hong Kong Chinese. The PPARG Pro12 risk allele contributed to increased risk for both T2D and CHD.