Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials
Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials
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DOI：
10.1016/j.jacc.2007.05.057
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发表时间：
2008-01-29
影响因子：
24
通讯作者：
Sacks, Frank M.
中科院分区：
文献类型：
--
作者：
Iakoubova, Olga A.;Tong, Carmen H.;Sacks, Frank M.
目的 我们询问先前发现与心血管疾病相关的 35 种基因多态性是否在 CARE（胆固醇和复发事件）试验中与心肌梗死 (MI) 相关，以及在 WOSCOPS（苏格兰西部冠状动脉预防研究）试验中与冠心病 (CHD) 相关，以及是否可以通过普伐他汀治疗降低与这些多态性相关的风险。 与 CHD 相关的遗传多态性可能会改善对 CHD 风险的评估和对疾病病理生理学的理解。 方法 我们使用针对传统危险因素进行调整的回归模型，测试了 CARE 研究中基因型与复发性 MI 之间的关联以及 WOSCOPS 试验中基因型与原发性 CHD 之间的关联：CARE 研究中的 Cox 比例风险模型和 WOSCOPS 嵌套病例对照研究中的条件 Logistic 回归模型 试验结果 我们发现 KIF6 中的 Trp719Arg (rs20455) 与冠状动脉事件相关。 KIF6 编码驱动蛋白样蛋白 6，它是分子运动超家族的成员。在接受安慰剂治疗的患者中，KIF6 719Arg 等位基因携带者（占 CARE 试验队列的 59.4%）在 CARE 试验中的风险比为 1.50（95% 置信区间 [CI] 1.05 至 2.15），在 WOSCOPS 试验中的比值比为 1.55（95% CI 1.14 至 2.09）。在携带者中，CARE 试验中普伐他汀的绝对风险降低率为 4.89%（95% CI 1.81% 至 7.97%），WOSCOPS 试验中为 5.49%（95% CI 3.52% 至 7.46%）。 结论 在 CARE 和 WOSCOPS 试验中，KIF6 719Arg 等位基因携带者发生冠状动脉事件的风险增加，并且普伐他汀治疗显着 降低了这种风险。
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.