Key result
Statin therapy cuts coronary events ~33% in KIF6 carriers, with no benefit for non-carriers.
Why the study?
A SNP in KIF6 is associated with differential coronary event reduction from statin therapy and risk for CHD, but the role of other common SNPs in KIF6 is unclear.
Do common SNPs in the KIF6 region predict coronary event reduction from statin therapy?
Observational (n=6,300)
Double-blind
Randomized in original trials
Yes
Do common SNPs in the KIF6 region predict coronary event reduction from statin therapy?
Specific SNPs in the KIF6 region (rs9462535, rs9471077, and rs20455) are associated with a significantly greater reduction in coronary events from statin therapy.
Answers are grounded in this paper and cite their sources.
KIF6 variants may guide statin response stratification; leaves open clinical adoption pending independent replication.
A single nucleotide polymorphism (SNP) in KIF6, a member of the KIF9 family of kinesins, is associated with differential coronary event reduction from statin therapy in four randomized controlled trials; this SNP (rs20455) is also associated with the risk for coronary heart disease (CHD) in multiple prospective studies. We investigated whether other common SNPs in the KIF6 region were associated with event reduction from statin therapy. Of the 170 SNPs in the KIF6 region investigated in the Cholesterol and Recurrent Events trial (CARE), 28 were associated with differential event reduction from statin therapy (P (interaction) < 01 in Caucasians, adjusted for age and sex) and were further investigated in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI22) and West of Scotland Coronary Prevention Study (WOSCOPS). These analyses revealed that two SNPs (rs9462535 and rs9471077), in addition to rs20455, were associated with event reduction from statin therapy (P (interaction) < 0.1 in each of the three studies). The relative risk reduction ranged from 37 to 50% (P < 0.01) in carriers of the minor alleles of these SNPs and from -4 to 13% (P > 0.4) in non-carriers. These three SNPs are in high linkage disequilibrium with one another (r (2) > 0.84). Functional studies of these variants may help to understand the role of KIF6 in the pathogenesis of CHD and differential response to statin therapy.
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Li et al. (2010) conducted an observational in Coronary heart disease (n=6,300). Statin therapy (pravastatin or atorvastatin) vs. Placebo or moderate statin therapy was evaluated on Fatal coronary event or nonfatal MI in CARE for KIF6 rs20455 carriers (HR 0.67, 95% CI 0.50-0.90, p=0.0074). Statin therapy reduced the relative risk of coronary events by 37% to 50% in carriers of KIF6 minor alleles (rs20455, rs9462535, rs9471077), whereas non-carriers experienced no significant benefit.
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