Cholesteryl ester transfer protein (CETP) I405V polymorphism and cardiovascular disease in eastern European Caucasians – a cross-sectional study

BACKGROUND The cholesteryl ester transfer protein (CETP) polymorphism I405V has been suggested to be involved in longevity and susceptibility to cardiovascular diseases. An enhanced reverse cholesterol transport due to enhanced HDL levels has been hypothesized to be the underlying mechanism. However, clinical trials with HDL-enhancing drugs failed to show beneficial effects. Consequently, it has been postulated that genetic variations enhancing HDL levels are cardioprotective only if they also decrease LDL levels. METHODS A cross-sectional study was conducted to genotype 1028 healthy blood donors and 1517 clinically well characterized elderly for CETP I405V. RESULTS We could not find any association of this polymorphism with age for both, males or females, in any of these cohorts (P = 0.71 and P = 0.57, respectively, for males and P = 0.55 and P = 0.88, respectively, for females). In addition, no association with cardiovascular diseases could be observed in the elderly cohort (males OR = 1.12 and females OR = 0.88). In the same cohort, the CETP V405V genotype was associated with significantly enhanced HDL levels (P = 0.03), mostly owing to the female sex (P = 0.46 for males, P = 0.02 for females), whereas LDL and triglyceride levels were unchanged (P = 0.62 and P = 0.18, respectively). CONCLUSION Our data support the recent hypothesis that variations enhancing HDL levels without affecting LDL levels are not associated with the risk for cardiovascular diseases.