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

• Published in: European journal of clinical investigation Vol. 31; no. 7; pp. 593 - 602
• Main Authors: Kakko, S., Tamminen, M., Päivänsalo, M., Kauma, H., Rantala, A. O., Lilja, M., Reunanen, A., Kesäniemi, Y. A., Savolainen, M. J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.2001; Blackwell; Blackwell Publishing Ltd
• Subjects: Adult; Arteriosclerosis - genetics; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Carotid Artery Diseases - genetics; Carrier Proteins - genetics; Cholesterol Ester Transfer Proteins; Cholesterol, HDL - blood; cholesteryl ester transfer protein; Female; genetic polymorphism; Genetic Variation; Glycoproteins; Haplotypes; high density lipoproteins; Humans; intima-media thickness; Linkage Disequilibrium; Male; Medical sciences; Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Promoter Regions, Genetic; Tunica Intima - pathology; Human; Cholesterolemia; Media; Cardiovascular disease; Epidemiology; Protein; Vascular disease; Ester; Gene; Cholesterol HDL; Atherosclerosis; Risk factor; Intima; Genetics; Biological effect; Vascular wall; Public health
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1046/j.1365-2362.2001.00859.x

Background Cholesteryl ester transfer protein (CETP) plays a major role in lipoprotein metabolism. We have screened the CETP gene for mutations and polymorphisms regulating high density lipoproteins cholesterol (HDL‐C) 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 the recently found functional polymorphism in the promoter region of the CETP gene (C to A, − 629 relative to the first transcribed nucleotide) explains the previous associations due to linkage disequilibrium. The genotypes were determined in a population sample of 481 men and women. Results There were no significant differences in plasma CETP activity or carotid IMT between the genotypes of the promoter polymorphism. The women with the CC genotype of the promoter polymorphism had the lowest HDL‐C levels (P < 0·001), but no such difference was seen in men. Detected polymorphisms of the CETP gene explained about 8% of the variation in HDL‐C in women and about 7 and 10% of the variation in carotid IMT in women and men, respectively. The associations of the promoter, I405V and R451Q‐A373P polymorphisms with HDL‐C and carotid IMT seemed to be independent of each other. The associations 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 polymorphisms explained a reasonable proportion of the variation in the degree of carotid atherosclerosis.