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.
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.
  
  
  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.
authors.affiliation: Department of Cardiology, Academic Medical Center, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: S M
authors.initials: SM
authors.lastname: Boekholdt
authors.forename: F M
authors.initials: FM
authors.lastname: Sacks
authors.forename: J W
authors.initials: JW
authors.lastname: Jukema
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
authors.forename: D J
authors.initials: DJ
authors.lastname: Freeman
authors.forename: A D
authors.initials: AD
authors.lastname: McMahon
authors.forename: F
authors.initials: F
authors.lastname: Cambien
authors.forename: V
authors.initials: V
authors.lastname: Nicaud
authors.forename: G J
authors.initials: GJ
authors.lastname: de Grooth
authors.forename: P J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
authors.forename: G J
authors.initials: GJ
authors.lastname: Miller
authors.forename: G
authors.initials: G
authors.lastname: Eiriksdottir
authors.forename: V
authors.initials: V
authors.lastname: Gudnason
authors.forename: H
authors.initials: H
authors.lastname: Kauma
authors.forename: S
authors.initials: S
authors.lastname: Kakko
authors.forename: M J
authors.initials: MJ
authors.lastname: Savolainen
authors.forename: M
authors.initials: M
authors.lastname: Arca
authors.forename: A
authors.initials: A
authors.lastname: Montali
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: H J
authors.initials: HJ
authors.lastname: Lanz
authors.forename: A H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: J A
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: J J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000517:prevention & control; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012306:Risk; D019914:Taq Polymerase
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019914:Taq Polymerase; D017035:Pravastatin