Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials.
OBJECTIVE
We asked whether 35 genetic polymorphisms, previously found to be associated with cardiovascular disease, were associated with myocardial infarction (MI) in the CARE (Cholesterol and Recurrent Events) trial and with coronary heart disease (CHD) in the WOSCOPS (West of Scotland Coronary Prevention Study) trial and whether the risk associated with these polymorphisms could be reduced by pravastatin treatment.


BACKGROUND
Identification of genetic polymorphisms associated with CHD may improve assessment of CHD risk and understanding of disease pathophysiology.


METHODS
We tested the association between genotype and recurrent MI in the CARE study and between genotype and primary CHD in the WOSCOPS trial using regression models that adjusted for conventional risk factors: Cox proportional hazards models for the CARE study and conditional logistic regression models for a nested case-control study of the WOSCOPS trial.


RESULTS
We found that Trp719Arg (rs20455) in KIF6 was associated with coronary events. KIF6 encodes kinesin-like protein 6, a member of the molecular motor superfamily. In placebo-treated patients, carriers of the KIF6 719Arg allele (59.4% of the CARE trial cohort) had a hazard ratio of 1.50 (95% confidence interval [CI] 1.05 to 2.15) in the CARE trial and an odds ratio of 1.55 (95% CI 1.14 to 2.09) in the WOSCOPS trial. Among carriers, the absolute risk reduction by pravastatin was 4.89% (95% CI 1.81% to 7.97%) in the CARE trial and 5.49% (95% CI 3.52% to 7.46%) in the WOSCOPS trial.


CONCLUSIONS
In both the CARE and the WOSCOPS trials, carriers of the KIF6 719Arg allele had an increased risk of coronary events, and pravastatin treatment substantially reduced that risk.
Iakoubova
Olga A
OA
Celera, Inc., Alameda, California 94502, USA. olga.iakoubova@celera.com
Tong
Carmen H
CH
Rowland
Charles M
CM
Kirchgessner
Todd G
TG
Young
Bradford A
BA
Arellano
Andre R
AR
Shiffman
Dov
D
Sabatine
Marc S
MS
Campos
Hannia
H
Packard
Christopher J
CJ
Pfeffer
Marc A
MA
White
Thomas J
TJ
Braunwald
Eugene
E
Shepherd
James
J
Devlin
James J
JJ
Sacks
Frank M
FM
D000924:Anticholesteremic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D003327:Coronary Disease / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000235:genetics*; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; C526774:KIF6 protein, human; D016547:Kinesins; D017035:Pravastatin