Genetics
13,677-subject meta-analysis confirms CETP TaqIB drives HDL and CAD risk but does not affect pravastatin response (Circulation 2005)
Original 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
This individual-patient meta-analysis combined data from 7 large population-based studies and 3 randomized placebo-controlled pravastatin trials to resolve inconsistent reports on the CETP TaqIB polymorphism. After adjustment for study, age, sex, smoking, BMI, diabetes, LDL-C, and alcohol use, B2B2 individuals had 0.11 mmol/L (0.10-0.12, P<0.0001) higher HDL-cholesterol than B1B1 individuals, and B2B2 genotype was associated with lower CAD risk (odds ratio 0.78, 0.66-0.93, P for linearity=0.008), an association that lost significance after further adjusting for HDL-C (P=0.4), indicating the CAD effect operates through HDL-C. No pharmacogenetic interaction between TaqIB genotype and pravastatin treatment could be demonstrated. The CETP TaqIB variant is thus firmly linked to HDL-C levels and, through that pathway, to CAD risk, but does not influence pravastatin's efficacy.
Original 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 >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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.