Objective: Type 2 diabetic patients have a high risk of coronary heart disease (CHD) and sudden death. This cardiovascular risk can be partly attributed to low levels of HDL cholesterol. The B2 allele of the CETP TaqIB polymorphism has been repeatedly reported to be associated with high HDL cholesterol 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 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 3,124 type 2 diabetic subjects with high cardiovascular risk: the Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study. We used Cox regression analysis to estimate the impact of the TaqIB single nucleotide polymorphism 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 cholesterol (P < 0.001), the association with sudden death persisted after adjustment for multiple risk factors, including HDL cholesterol levels.
Conclusions: In type 2 diabetic patients, the CETP TaqIB polymorphism is a good genetic predictor of cardiac mortality. This association is partly independent of the effect on HDL cholesterol levels.