Thrombomodulin gene polymorphisms and haplotypes and the risk of cardiovascular events - A prospective follow-up study
Thrombomodulin gene polymorphisms and haplotypes and the risk of cardiovascular events - A prospective follow-up study
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DOI：
10.1161/01.atv.0000208365.45200.41
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发表时间：
2006-04-01
影响因子：
8.7
通讯作者：
Salomaa, V
中科院分区：
文献类型：
--
作者：
Auro, K;Komulainen, K;Salomaa, V
背景-血栓调节蛋白是在内皮激活和损伤期间表达的抗凝剂。为了解决血栓调节蛋白基因等位基因变异在心血管疾病发病机制中的潜在作用，我们在一项前瞻性随访研究中分析了血栓调节蛋白基因座的 8 个单核苷酸多态性 (SNP)，涵盖所有常见 (> 5%) 单倍型。 方法和结果 - 1992 年和 1997 年在芬兰检查了 25 至 74 岁男性和女性的两个独立分层随机样本。样本量为 14 140 人，随访期为 7 年（1997 年队列）至 10 年（1992 年队列）。总共有 662 人在基线时就有心血管事件史。在随访期间，观察到 401 例冠状动脉事件和 148 例缺血性中风事件。使用冠状动脉事件、缺血性中风事件和总死亡率作为终点，在 Cox 比例风险模型中测试 8 个 SNP 的等位基因和常见单倍型。没有一个 SNP 或主要 SNP 单倍型与合并数据中分析的终点显示出一致的关联。 结论——这项基于人群的前瞻性研究的结果表明，血栓调节蛋白基因的常见等位基因变异可能不会显着增加人群水平的心血管事件风险。
Background-Thrombomodulin is an anticoagulant expressed during endothelial activation and damage. To address the potential role of allelic variants of thrombomodulin gene in the pathogenesis of cardiovascular diseases, we analyzed in a prospective follow-up study 8 single-nucleotide polymorphisms (SNPs) across the thrombomodulin locus, covering all common (> 5%) haplotypes.Methods and Results-Two separate, stratified random samples of men and women 25 to 74 years of age were examined in Finland in 1992 and 1997. The total sample size was 14 140 individuals, with 7 (1997 cohort) to 10 (1992 cohort) years of follow-up. Altogether, 662 individuals had a history of cardiovascular events already at baseline. During the follow-up, 401 incident coronary events and 148 incident ischemic strokes were observed. The alleles and common haplotypes of 8 SNPs were tested in Cox proportional hazards models using incident coronary events, incident ischemic strokes, and total mortality as end points. None of the SNPs or major SNP haplotypes showed consistent association with the end points analyzed in the combined data.Conclusions-Results from this prospective, population-based study suggest that common allelic variants of the thrombomodulin gene may not significantly contribute to the risk of cardiovascular events at the population level.