Boekholdt, SM and Sacks, FM and Jukema, JW and Shepherd, J and Freeman, DJ and McMahon, AD and Cambien, F and Nicaud, V and de Grooth, GJ and Talmud, PJ and Humphries, SE and Miller, GJ and Eiriksdottir, G and Gudnason, V and Kauma, H and Kakko, S and Savolainen, MJ and Arca, M and Montali, A and Liu, S and Lanz, HJ and Zwinderman, AH and Kuivenhoven, JA and Kastelein, JJP (2005) 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. CIRCULATION , 111 (3) 278 - 287. 10.1161/01.CIR.0000153341.46271.40.
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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.
|Title:||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|
|Keywords:||genetics, cholesterol, lipoproteins, coronary disease, CORONARY-HEART-DISEASE, PLASMA HDL-CHOLESTEROL, MIDDLE-AGED MEN, CETP GENE, MYOCARDIAL-INFARCTION, ARTERY-DISEASE, SUBFRACTION DISTRIBUTION, PROMOTER POLYMORPHISM, ENVIRONMENTAL-FACTORS, ASSOCIATION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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