Cholesteryl Ester Transfer Protein TaqIB Variant, High-Density Lipoprotein Cholesterol Levels, Cardiovascular Risk, and Efficacy of Pravastatin Treatment

Abstract

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 Ͼ500 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, PϽ0.0001) 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 ratioϭ0.78 [0.66 to 0.93]) in B2B2 individuals compared with B1B1 individuals (P for linearityϭ0.008). Additional adjustment for HDL-C levels rendered a loss of statistical significance (Pϭ0.4). 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. (Circulation. 2005;111: 278-287.)

Association of the CETP TaqIB Polymorphism with Coronary Artery Disease in Type 2 Diabetic Patients

“…The findings of a meta-analysis demonstrated an increased incidence of cardiovascular disease in spite of the increase of HDL-C levels in homozygous B2B2 (28). There are contradictory results on the relationship between different genotypes of TaqIB polymorphism and HDL-C levels in diabetic patients.…”

Clinical implications of pharmacogenomics of statin treatment

“…Variation in this gene, particularly a TaqIB variant located within intron 1, has been reported to be associated with plasma HDL concentration and CVD risk under basal conditions. 74,75 Many studies have examined the influence of the TaqIB variant on statin response. Initial reports suggesting that TaqIB is associated with variation in HDLC response and CVD disease end points have failed to replicate.…”

Candidate Gene Genotypes, Along with Conventional Risk Factor Assessment, Improve Estimation of Coronary Heart Disease Risk in Healthy UK Men

“…Our a priori hypothesis was that risk prediction would not be significantly improved, because of the low reported risk associated with any particular SNP, the low prevalence of risk genotypes, and the fact that many of the genes will be influencing CHD through factors already in the CRF algorithm. Thus, although metaanalysis demonstrates a significant impact of CETP genotype on risk, this effect was considerably attenuated (and no longer statistically significant) by adjustment for HDL concentrations (9 ), demonstrating that CHD-risk genotypes will not necessarily improve prediction over CRFs. APOE did so singly, however, and the combination of SNPs in the genes for UCP2, APOA4, and LPL with APOE improved prediction further.…”

“…Although many candidate genes for CHD have been tested (7 ), the optimal set of risk genotypes has yet to be identified. Only a relatively modest risk can be expected in association with any single genotype; published estimates are in the range 1.2-1.4 (6,8,9 ). Furthermore, given the multifactorial nature of CHD, lifestyle will set the operational context for genetic variants.…”