Abstract 2179: No Impact of KIF6 Genotype on Vascular Risk or Statin Benefit in the Heart Protection Study
The KIF6 719Arg (rs20455) variant has been reported to be associated with up to a 50% higher relative risk of coronary heart disease (CHD). It has also been suggested that the relative reduction in CHD rate with statin therapy varies by genotype: 50% (95%CI: 33% to 62%) in 719Arg carriers vs 6% (95%CI: −33% to 33%) in non-carriers. The large Heart Protection Study (HPS), in which high-risk patients were randomly allocated simvastatin 40 mg daily vs placebo and followed for a mean of 5 years, allowed reliable assessment of the effects of this variant on vascular outcomes and statin efficacy. Among 3945 genotyped participants, 984 (25%) had major vascular events (MVE) and 447 (11%) had major coronary events (MCE). By contrast to previous reports (involving fewer events), there were not significant associations of the 719Arg variant with rates of MVEs (1.03 [95%CI: 0.87 to 1.22]; p=0.7) or of MCEs (1.17 [95%CI: 0.92 to 1.50]; p=0.2) in the placebo group. Irrespective of the rs20455 genotype, allocation to simvastatin reduced MVE rate by 30% (95%CI: 21% to 39%). There was no significant heterogeneity between the relative reduction in MVE rate among 719Arg variant carriers (33% reduction [95%CI: 22% to 43%]) vs non-carriers (26% reduction [95%CI: 10% to 39%]), either in dominant (p=0.4) or additive (p=0.3) models. Nor was genotype significantly associated with the LDL-cholesterol reduction produced by simvastatin (p=0.2). These results suggest that statin therapy produces substantial reductions in MVE rate irrespective of rs20455 genotype, and that any tendency towards a greater risk of MVEs or greater effect of statin in carriers of the 719Arg variant is less marked than previously reported.