title: Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials.
abstract: OBJECTIVE
  We asked whether 35 genetic polymorphisms, previously found to be associated with cardiovascular disease, were associated with myocardial infarction (MI) in the CARE (Cholesterol and Recurrent Events) trial and with coronary heart disease (CHD) in the WOSCOPS (West of Scotland Coronary Prevention Study) trial and whether the risk associated with these polymorphisms could be reduced by pravastatin treatment.
  
  
  BACKGROUND
  Identification of genetic polymorphisms associated with CHD may improve assessment of CHD risk and understanding of disease pathophysiology.
  
  
  METHODS
  We tested the association between genotype and recurrent MI in the CARE study and between genotype and primary CHD in the WOSCOPS trial using regression models that adjusted for conventional risk factors: Cox proportional hazards models for the CARE study and conditional logistic regression models for a nested case-control study of the WOSCOPS trial.
  
  
  RESULTS
  We found that Trp719Arg (rs20455) in KIF6 was associated with coronary events. KIF6 encodes kinesin-like protein 6, a member of the molecular motor superfamily. In placebo-treated patients, carriers of the KIF6 719Arg allele (59.4% of the CARE trial cohort) had a hazard ratio of 1.50 (95% confidence interval [CI] 1.05 to 2.15) in the CARE trial and an odds ratio of 1.55 (95% CI 1.14 to 2.09) in the WOSCOPS trial. Among carriers, the absolute risk reduction by pravastatin was 4.89% (95% CI 1.81% to 7.97%) in the CARE trial and 5.49% (95% CI 3.52% to 7.46%) in the WOSCOPS trial.
  
  
  CONCLUSIONS
  In both the CARE and the WOSCOPS trials, carriers of the KIF6 719Arg allele had an increased risk of coronary events, and pravastatin treatment substantially reduced that risk.
authors.affiliation: Celera, Inc., Alameda, California 94502, USA. olga.iakoubova@celera.com
authors.forename: Olga A
authors.initials: OA
authors.lastname: Iakoubova
authors.forename: Carmen H
authors.initials: CH
authors.lastname: Tong
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rowland
authors.forename: Todd G
authors.initials: TG
authors.lastname: Kirchgessner
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Young
authors.forename: Andre R
authors.initials: AR
authors.lastname: Arellano
authors.forename: Dov
authors.initials: D
authors.lastname: Shiffman
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.forename: Hannia
authors.initials: H
authors.lastname: Campos
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Packard
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: White
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: James
authors.initials: J
authors.lastname: Shepherd
authors.forename: James J
authors.initials: JJ
authors.lastname: Devlin
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D003327:Coronary Disease / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000235:genetics*; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; C526774:KIF6 protein, human; D016547:Kinesins; D017035:Pravastatin