Variation at the cholesteryl ester transfer protein gene in relation to plasma high density lipoproteins cholesterol levels and carotid intima-media thickness

Background Cholesteryl ester transfer protein (CETP) plays a major role in lipoprotein metabolism. We have screened the CETP gene for mutations and po lymorphisms regulating high density lipoproteins cholesterol (HDLC) levels and the development of atherosclerosis, and found some polymorphisms (I405V and R451Q) to have minor effects. Design The purpose of this study was to investigate the combined effect of the several polymorphisms of the CETP gene so far found on HDL-C levels and carotid intima-media thickness (IMT), and, in addition, to study whether t he recently found functional polymorphism in the promoter region of the CET P gene (C to A, - 629 relative to the first transcribed nucleotide) explain s the previous associations due to linkage disequilibrium. The genotypes we re determined in a population sample of 481 men and women. Results There were no significant differences in plasma CETP activity or ca rotid IMT between the genotypes of the promoter polymorphism. The women wit h the CC genotype of the promoter polymorphism had the lowest HDLC levels ( P < 0001), but no such difference was seen in men. Detected polymorphisms o f the CETP gene explained about 8% of the variation in HDLC in women and ab out 7 and 10% of the variation in carotid IMT in women and men, respectivel y. The associations of the promoter, I405V and R451Q-A373P polymorphisms wi th HDL-C and carotid IMT seemed to be independent of each other. The associ ations with IMT were independent of total HDL-C levels, suggesting that HDL subfractions may have more effect on IMT. Conclusion The CETP gene locus was found to be polymorphic and its polymorp hisms explained a reasonable proportion of the variation in the degree of c arotid atherosclerosis.