title: Effect of pravastatin therapy on coronary events in carriers of the KIF6 719Arg allele from the cholesterol and recurrent events trial.
abstract: A previous genetic analysis of the Cholesterol and Recurrent Events (CARE) trial found that carriers of the 719Arg allele of the kinesin family member 6 gene (KIF6) (rs20455), but not noncarriers, received significant event reduction from pravastatin therapy. However, that previous analysis of CARE included only Caucasian patients and was limited to the myocardial infarction components of the primary end point. Therefore, the aim of this study was to investigate whether pravastatin therapy reduced primary end point events in KIF6 719Arg carriers and noncarriers, separately, in the combined ethnic groups of CARE. The effect of pravastatin therapy on primary end point events (fatal coronary event or nonfatal myocardial infarction) was investigated in Cox regression models that adjusted for population structure using either self-reported ethnicity or the principal components of genetic heterogeneity. After adjustment for age, gender, and self-reported ethnicity, pravastatin therapy reduced events in carriers of KIF6 719Arg (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.49 to 0.83) but not in noncarriers (HR 1.01, 95% CI 0.69 to 1.45) (p for interaction = 0.049). After adjustment for age, gender, traditional risk factors, and principal components, pravastatin therapy reduced events in carriers of 719Arg (HR 0.64, 95% CI 0.49 to 0.85) but not in noncarriers (HR 0.90, 95% CI 0.62 to 1.32) (p for interaction = 0.14). In conclusion, in an analysis that included CARE patients of all ethnic groups, pravastatin therapy significantly and substantially reduced primary end point events in carriers of the KIF6 719Arg allele but not in noncarriers.
authors.affiliation: Celera, Alameda, CA, USA. dov.shiffman@celera.com
authors.forename: Dov
authors.initials: D
authors.lastname: Shiffman
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.forename: Judy Z
authors.initials: JZ
authors.lastname: Louie
authors.forename: Todd G
authors.initials: TG
authors.lastname: Kirchgessner
authors.forename: Olga A
authors.initials: OA
authors.lastname: Iakoubova
authors.forename: Hannia
authors.initials: H
authors.lastname: Campos
authors.forename: James J
authors.initials: JJ
authors.lastname: Devlin
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
mesh_terms: D000483:Alleles; D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D004247:DNA / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016547:Kinesins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D055502:Secondary Prevention; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D004247:DNA; D002784:Cholesterol; C526774:KIF6 protein, human; D016547:Kinesins; D017035:Pravastatin