Genetic variants in the KIF6 region and coronary event reduction from statin therapy.
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.
Li
Yonghong
Y
yonghong.li@celera.com
Sabatine
Marc S
MS
Tong
Carmen H
CH
Ford
Ian
I
Kirchgessner
Todd G
TG
Packard
Christopher J
CJ
Robertson
Michele
M
Rowland
Charles M
CM
Bare
Lance A
LA
Shepherd
James
J
Devlin
James J
JJ
Iakoubova
Olga A
OA
D002874:Chromosome Mapping; D003327:Coronary Disease / Q000188:drug therapy* / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016547:Kinesins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C526774:KIF6 protein, human; D016547:Kinesins