Abstract

OBJECTIVES - Type 2 diabetic patients are at high risk of CHD and sudden death. This cardiovascular risk can be partly attributed to low levels of HDL-cholesterol (HDL-C). The B2 allele of the CETP TaqIB polymorphism has been repeatedly reported to be associated with high HDL -C levels in both healthy and type 2 diabetic subjects, but its association with CHD is unclear. We investigated the association of the CETP TaqIB polymorphism with coronary heart disease (CHD), and sudden death in particular, in a prospective cohort of type 2 diabetic patients.

RESEARCH DESIGN AND METHODS - The CETP TaqIB polymorphism was genotyped in 3124 type 2 diabetic subjects with high cardiovascular risk: the DIABHYCAR study. We used Cox regression analysis to estimate the impact of the TaqIB SNP on the CHD events (myocardial infarction or sudden death) during follow-up.

RESULTS - The incidence of CHD was higher in B1B1 homozygotes than in B2 carriers (P = 0.02). This effect was mainly due to sudden death: hazard ratio (B1B1 vs B2+) = 1.51 [95% CI = 1.05-2.18]. Although the B1 allele was associated in a dose-dependent fashion with lower HDL-C (P < 0.001), the association with sudden death persisted after adjusting for multiple risk factors, including HDL-C levels.

CONCLUSION - In type 2 diabetic patients, the CETP TaqI B polymorphism is a good genetic predictor of cardiac mortality. This association is partly independent of the effect on HDL-C levels.