title: No impact of KIF6 genotype on vascular risk and statin response among 18,348 randomized patients in the heart protection study.
abstract: OBJECTIVE
  The aim of this study was to test the effects of the KIF6 Trp719Arg polymorphism (rs20455) on vascular risk and response to statin therapy in 18,348 participants from the Heart Protection Study.
  
  
  BACKGROUND
  There have been claims that noncarriers of the KIF6 719Arg variant receive little benefit from statin therapy. Screening for this genetic variant is now being used to influence statin use.
  
  
  METHODS
  Participants received 40 mg simvastatin daily for 4 to 6 weeks before being randomly allocated 40 mg simvastatin daily or placebo for 5 years. Major coronary event was pre-defined as coronary death or nonfatal myocardial infarction, and major vascular event was pre-defined as major coronary event plus revascularization or stroke.
  
  
  RESULTS
  The KIF6 genotype was not significantly associated, among placebo-allocated participants, with the risks of incident major vascular events, major coronary events, revascularizations, or strokes. Overall, 40 mg simvastatin daily produced a 42% reduction in low-density lipoprotein cholesterol, which did not differ significantly by KIF6 719Arg carrier status (p = 0.51). Proportional reductions in the risk of major vascular events with statin therapy were similar (interaction p = 0.70) and highly significant across KIF6 genotypes: 23% (95% confidence interval: 16% to 29%; p = 5.3 × 10⁻¹⁰) in carriers (Arg/Arg or Trp/Arg), and 24% (95% confidence interval: 17% to 31%; p = 4.6 × 10⁻⁹) in noncarriers (Trp/Trp). A similar lack of interaction was observed for major coronary events, revascularizations, and strokes considered separately.
  
  
  CONCLUSIONS
  Statin therapy significantly reduces the incidence of coronary and other major vascular events to a similar extent, irrespective of KIF6 genotype. Consequently, the use of KIF6 genotyping to guide statin therapy is not warranted. (Heart Protection Study; ISRCTN48489393).
authors: Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK. Jemma.Hopewell@ctsu.ox.ac.uk
authors: Jemma C
authors: JC
authors: Hopewell
authors: Sarah
authors: S
authors: Parish
authors: Robert
authors: R
authors: Clarke
authors: Jane
authors: J
authors: Armitage
authors: Louise
authors: L
authors: Bowman
authors: Jorg
authors: J
authors: Hager
authors: Mark
authors: M
authors: Lathrop
authors: Rory
authors: R
authors: Collins
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control*; D005260:Female; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016547:Kinesins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C526774:KIF6 protein, human; D016547:Kinesins