Published online before print January 17, 2005, doi: 10.1161/01.CIR.0000153341.46271.40
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(Circulation. 2005;111:278-287.)
© 2005 American Heart Association, Inc.
Coronary Heart Disease |
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
From the Departments of Cardiology (S.M.B.), Vascular Medicine (G.J.d.G., J.A.K., J.J.P.K.), and Clinical Epidemiology and Biostatistics (A.H.Z.), Academic Medical Center, Amsterdam, the Netherlands; Nutrition Department (F.M.S.), Harvard School of Public Health, Boston, Mass; Department of Cardiology (J.W.J.), Leiden University Medical Center, Leiden, the Netherlands; Department of Pathological Biochemistry (J.S.), Glasgow Royal Infirmary, Glasgow, Scotland; Division of Developmental Medicine (D.J.F.) and Robertson Centre for Biostatistics (A.D.M.), University of Glasgow, Glasgow, Scotland; Institut National de la Santé et de la Recherche Médicale Unité 525 (V.N., F.C.), Paris, France; Division of Cardiovascular Genetics (P.J.T., S.E.H.), Department of Medicine, Royal Free and University College Medical School, London, England; MRC Cardiovascular Research Group (G.J.M.), Wolfson Institute of Preventive Medicine, St. Bartholomew’s and Royal London School of Medicine, London, England; Hjartavernd Research Institute (G.E., V.G.), Icelandic Heart Association, Kopavogur, Iceland; Department of Internal Medicine (H.K., S.K., M.J.S.), University of Oulu, Oulu, Finland; Department of Clinical and Applied Medical Therapy (M.A., A.M.), University of Rome La Sapienza, Rome, Italy; Division of Preventive Medicine (S.L.), Harvard Medical School and Brigham and Women’s Hospital, Boston, Mass; and Bristol-Myers Squibb Co (H.J.L.), Princeton, NJ.
Correspondence to John J.P. Kastelein, MD, PhD, Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail e.vandongen{at}amc.uva.nl
Received April 22, 2004; revision received September 13, 2004; accepted September 24, 2004.
Background— 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.
Methods and Results— 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.
Conclusions— 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.
Key Words: genetics • cholesterol • lipoproteins • coronary disease
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