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.
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Iakoubova OA, Tong CH, Rowland CM, Kirchgessner TG, Young BA, Arellano AR, Shiffman D, Sabatine MS, Campos H, Packard CJ, Pfeffer MA, White TJ, Braunwald E, Shepherd J, Devlin JJ, Sacks FM
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. 2008 Jan 29;51(4):435-43. doi: 10.1016/j.jacc.2007.05.057.
- PubMed ID
- 18222353 [ View in PubMed]
- Abstract
OBJECTIVES: 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.
DrugBank Data that Cites this Article
- Pharmaco-genomics
Drug Interacting Gene/Enzyme Allele name Genotypes Defining change(s) Type(s) Description Details Pravastatin Kinesin-like protein KIF6
Gene symbol: KIF6
UniProt: Q6ZMV9--- (C;C) / (C;T) - C Allele (rs20455)
Effect Directly Studied Patients with this genotype have a greater reduction in risk of a major cardiovascular event with high dose pravastatin. Details Simvastatin Kinesin-like protein KIF6
Gene symbol: KIF6
UniProt: Q6ZMV9--- (C;C) / (C;T) - C Allele (rs20455)
Effect Directly Studied Patients with this genotype have a greater reduction in risk of a major cardiovascular event with high dose simvastatin. Details Atorvastatin Kinesin-like protein KIF6
Gene symbol: KIF6
UniProt: Q6ZMV9--- (C;C) / (C;T) - C Allele (rs20455)
Effect Directly Studied Patients with this genotype have a greater reduction in risk of a major cardiovascular event with high dose atorvastatin. Details Rosuvastatin Kinesin-like protein KIF6
Gene symbol: KIF6
UniProt: Q6ZMV9--- (C;C) / (C;T) - C Allele (rs20455)
Effect Directly Studied Patients with this genotype have a greater reduction in risk of a major cardiovascular event with high dose rosuvastatin. Details