CETP TaqIB fails to protect against coronary heart disease over 10 years despite raising HDL cholesterol, and even raises risk in drinkers (Atherosclerosis 2010)

Objective: Despite the consistent association between cholesteryl ester transfer protein (CETP) gene variation and plasma HDL-C, huge controversy still rages on its association with coronary heart disease (CHD). We investigated the association between the CETP-TaqIB polymorphism, HDL-C and incident CHD in a Mediterranean population.

Methods: A nested case-control study among participants of the Spanish EPIC cohort was performed. 41,440 healthy individuals (30-69 years) were followed up over a 10-year period, incident CHD cases being identified. We analyzed 557 confirmed CHD cases and 1180 healthy controls.

Results: Despite B2B2 subjects having the highest HDL-C concentrations and B1B1, the lowest (P<0.001), no protective effect of the B2 allele against CHD incidence was observed. Thus, in comparison with B1B1 subjects, the adjusted CHD risk of B1B2 was OR: 1.00, 95% CI: 0.80-1.26; P=0.982, and that of B2B2 was OR: 1.16, 95% CI: 0.84-1.61; P=0.374. These results did not change after adjustment for HDL-C. No significant interaction between alcohol consumption and the CETP-TaqIB polymorphism in determining HDL-C was found. However, a different effect of this polymorphism on CHD risk in drinkers and non-drinkers was observed. In non-drinkers, the B2B2 genotype was associated with a non-significant lower CHD risk, whereas in drinkers it was associated with a greater risk (OR: 1.55, 95% CI: 1.05-2.29; P=0.026). We also observed that in diabetics (11% cases and 7.4% controls), the B2 allele was significantly associated with higher CHD risk.

Conclusions: In this Mediterranean population, the CETP-TaqIB polymorphism was not associated with a lower CHD incidence, and its effect was modulated by alcohol and possibly by diabetes.