Gene variants associated with ischemic stroke: the cardiovascular health study.
Gene variants associated with ischemic stroke: the cardiovascular health study.
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DOI：
10.1161/strokeaha.108.521328
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发表时间：
2009-02
期刊：
影响因子：
8.3
通讯作者：
Psaty BM
中科院分区：
文献类型：
--
作者：
Luke MM;O'Meara ES;Rowland CM;Shiffman D;Bare LA;Arellano AR;Longstreth WT Jr;Lumley T;Rice K;Tracy RP;Devlin JJ;Psaty BM
本研究的目的是确定74个单核苷酸多态性（SNPs），这已经与冠心病，是否与缺血性卒中事件。基于冠心病的前期研究，我们预先确定了74个SNP中每一个的风险等位基因。我们使用考克斯比例风险模型，调整传统的危险因素，以估计这些SNP与缺血性卒中事件的关联，在14年的随访中，在老年人的人群为基础的研究：心血管健康研究（CHS）。在白色CHS受试者中，74个SNP中的7个（HPS 1、ITGAE、ABCG 2、MYH 15、FSTL 4、CALM 1和BAT 2）的预先指定的风险等位基因与卒中风险增加名义上相关（单侧P<0.05，错误发现率=0.42）。在黑人受试者中，5个SNP（KRT 4、LY 6 G5 B、EDG 1、DMXL 2和ABCG 2）的预先设定的风险等位基因与卒中名义上相关（单侧P<0.05，错误发现率=0.55）。在CHS的白色和黑色受试者中，ABCG 2中的Val 12 Met SNP与卒中相关（风险比，1.46; 90% CI，1.05至2.03）和（风险比，3.59; 90% CI，1.11至11.6）。在CHS的白色和黑色受试者中，瓦尔等位基因纯合子的10年累积卒中发病率的Kaplan-Meier估计值均高于Met等位基因携带者（10%对6%）和（12%对3%）。ABCG 2（编码固醇和外源性物质的转运蛋白）中的Val 12 Met SNP与CHS的白色和黑人参与者中的缺血性卒中事件相关。
The purpose of this study was to determine whether 74 single nucleotide polymorphisms (SNPs), which had been associated with coronary heart disease, are associated with incident ischemic stroke. Based on antecedent studies of coronary heart disease, we prespecified the risk allele for each of the 74 SNPs. We used Cox proportional hazards models that adjusted for traditional risk factors to estimate the associations of these SNPs with incident ischemic stroke during 14 years of follow-up in a population-based study of older adults: the Cardiovascular Health Study (CHS). In white CHS participants, the prespecified risk alleles of 7 of the 74 SNPs (in HPS1, ITGAE, ABCG2, MYH15, FSTL4, CALM1, and BAT2) were nominally associated with increased risk of stroke (one-sided P<0.05, false discovery rate=0.42). In black participants, the prespecified risk alleles of 5 SNPs (in KRT4, LY6G5B, EDG1, DMXL2, and ABCG2) were nominally associated with stroke (one-sided P<0.05, false discovery rate=0.55). The Val12Met SNP in ABCG2 was associated with stroke in both white (hazard ratio, 1.46; 90% CI, 1.05 to 2.03) and black (hazard ratio, 3.59; 90% CI, 1.11 to 11.6) participants of CHS. Kaplan-Meier estimates of the 10-year cumulative incidence of stroke were greater among Val allele homozygotes than among Met allele carriers in both white (10% versus 6%) and black (12% versus 3%) participants of CHS. The Val12Met SNP in ABCG2 (encoding a transporter of sterols and xenobiotics) was associated with incident ischemic stroke in white and black participants of CHS.