Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: Individual patient meta-analysis of 13 677 subjects

• Published in: Circulation (New York, N.Y.) Vol. 111; no. 3; pp. 278 - 287
• Main Authors: BOEKHOLDT, S. M, SACKS, F. M, HUMPHRIES, S. E, MILLER, G. J, EIRIKSDOTTIR, G, GUDNASON, V, KAUMA, H, KAKKO, S, SAVOLAINEN, M. J, ARCA, M, MONTALI, A, LIU, S, JUKEMA, J. W, LANZ, H. J, ZWINDERMAN, A. H, KUIVENHOVEN, J. A, KASTELEIN, J. J. P, SHEPHERD, J, FREEMAN, D. J, MCMAHON, A. D, CAMBIEN, F, NICAUD, V, DE GROOTH, G. J, TALMUD, P. J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 25.01.2005
• Subjects: Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - prevention & control; Carrier Proteins - genetics; Cholesterol Ester Transfer Proteins; Cholesterol, HDL - blood; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Glycoproteins - genetics; Heart; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Medical sciences; Polymorphism, Genetic; Pravastatin - therapeutic use; Randomized Controlled Trials as Topic; Regression Analysis; Risk; Taq Polymerase; Human; Enzyme; Enzyme inhibitor; Lipids; Cardiovascular disease; Statin derivative; Lipoprotein; Pravastatin; Coronary heart disease; Cholesterol; Vascular disease; coronary disease; Treatment; genetics; Atherosclerosis; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; lipoproteins; Antilipemic agent
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000153341.46271.40

Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD), but the results are inconsistent. In addition, an interaction has been implicated between this genetic variant and pravastatin treatment, but this has not been confirmed. A meta-analysis was performed on individual patient data from 7 large, population-based studies (each >500 individuals) and 3 randomized, placebo-controlled, pravastatin trials. Linear and logistic regression models were used to assess the relation between TaqIB genotype and HDL-C levels and CAD risk. After adjustment for study, age, sex, smoking, body mass index (BMI), diabetes, LDL-C, use of alcohol, and prevalence of CAD, TaqIB genotype exhibited a highly significant association with HDL-C levels, such that B2B2 individuals had 0.11 mmol/L (0.10 to 0.12, P<0.0001) higher HDL-C levels than did B1B1 individuals. Second, after adjustment for study, sex, age, smoking, BMI, diabetes, systolic blood pressure, LDL-C, and use of alcohol, TaqIB genotype was significantly associated with the risk of CAD (odds ratio=0.78 [0.66 to 0.93]) in B2B2 individuals compared with B1B1 individuals (P for linearity=0.008). Additional adjustment for HDL-C levels rendered a loss of statistical significance (P=0.4). Last, no pharmacogenetic interaction between TaqIB genotype and pravastatin treatment could be demonstrated. The CETP TaqIB variant is firmly associated with HDL-C plasma levels and as a result, with the risk of CAD. Importantly, this CETP variant does not influence the response to pravastatin therapy.