Iakoubova OA et al. (2008) 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. J Am Coll Cardiol 51: 435–443

A large number of genetic polymorphisms have been linked with cardiovascular disease; however, few of these associations have been validated in independent studies. In a recent investigation, Iakoubova et al. conducted genetic association analyses to determine whether any of 35 polymorphisms previously shown to have an association with cardiovascular disease were associated with myocardial infarction (MI) in the placebo arm of the CARE trial, or with coronary heart disease (CHD) in the placebo arm of the WOSCOPS trial.

The researchers identified four single-nucleotide polymorphisms that were associated with MI in the CARE population and two single-nucleotide polymorphisms that were associated with CHD in the WOSCOPS population. Once the evidence from the two trials was combined and a multiple testing correction was applied, however, only a Trp719Arg polymorphism in the gene that encodes kinesin-like protein 6 (KIF6) remained significantly associated with coronary events. In the placebo arm of the CARE trial, carriers of this polymorphism had an increased risk of recurrent MI even after adjustment for age, sex, smoking history, BMI, cholesterol level, hypertension, and diabetes mellitus (hazard ratio 1.50, 95% CI 1.05–2.15). The risk of CHD in carriers of the KIF6 719Arg allele in the placebo arm of the WOSCOPS trial was similarly increased after adjustment for conventional risk factors (odds ratio 1.55, 95% CI 1.14–2.09). Further analyses revealed that pravastatin treatment markedly lowered the risk of coronary events in carriers of the KIF6 719Arg allele in both trials.