title: KIF6 Trp719Arg polymorphism and the effect of statin therapy in elderly patients: results from the PROSPER study.
abstract: BACKGROUND
  Statin therapy has been found to substantially and significantly reduce coronary events in carriers of the KIF6 719Arg variant (rs20455) but not in noncarriers. We investigated whether, among the elderly, statin therapy also significantly reduced coronary events in carriers but not in noncarriers.
  
  
  METHODS
  Among 5,752 patients of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study, we assessed the effect of pravastatin, compared with placebo, on coronary events according to 719Arg carrier status using proportional hazards models.
  
  
  RESULTS
  Since benefit from statin therapy in elderly patients has been primarily shown among those with prior vascular disease, we performed analyses in PROSPER patients with prior disease and found that pravastatin therapy significantly reduced events in 719Arg carriers [hazards ratio (HR): 0.66, 95% confidence interval (CI): 0.52-0.86] but not in noncarriers (HR: 0.94, 95% CI: 0.69-1.28), P=0.09 for interaction between treatment and carrier status. Among those without prior disease, no significant benefit was observed in either carriers or noncarriers. Among those with prior vascular disease in the placebo arm, Trp719Arg heterozygotes were at significantly greater risk, compared with noncarriers (HR: 1.36, 95% CI: 1.03-1.81, P=0.03); the HR of 719Arg carriers, compared with noncarriers, was 1.28 (95% CI: 0.98-1.69, P=0.07).
  
  
  CONCLUSIONS
  Elderly carriers of the KIF6 719Arg variant with prior vascular disease received significant benefit from pravastatin therapy; no benefit was observed in noncarriers with prior disease or in those without prior disease (carriers or noncarriers).
authors.affiliation: Celera, Inc., 1401 Harborbay Pkwy, Alameda, CA 94502, USA. olga.iakoubova@celera.com
authors.forename: Olga A
authors.initials: OA
authors.lastname: Iakoubova
authors.forename: Michele
authors.initials: M
authors.lastname: Robertson
authors.forename: Carmen H
authors.initials: CH
authors.lastname: Tong
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rowland
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Catanese
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Blauw
authors.forename: J W
authors.initials: JW
authors.lastname: Jukema
authors.forename: Michael B
authors.initials: MB
authors.lastname: Murphy
authors.forename: James J
authors.initials: JJ
authors.lastname: Devlin
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.forename: James
authors.initials: J
authors.lastname: Shepherd
mesh_terms: D000367:Age Factors; D000368:Aged; D003327:Coronary Disease / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016547:Kinesins / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C526774:KIF6 protein, human; D016547:Kinesins; D017035:Pravastatin