Luke May M, O'Meara Ellen S, Rowland Charles M, Shiffman Dov, Bare Lance A, Arellano Andre R, Longstreth W T, Lumley Thomas, Rice Kenneth, Tracy Russell P, Devlin James J, Psaty Bruce M
Celera, Alameda, California 94502, USA.
Stroke. 2009 Feb;40(2):363-8. doi: 10.1161/STROKEAHA.108.521328. Epub 2008 Nov 20.
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.
本研究旨在确定74个曾与冠心病相关的单核苷酸多态性（SNP）是否与缺血性卒中的发生相关。
基于先前对冠心病的研究，我们预先确定了74个SNP中每个SNP的风险等位基因。在一项针对老年人的基于人群的研究——心血管健康研究（CHS）中，我们使用经传统风险因素校正的Cox比例风险模型，来估计这些SNP与14年随访期间缺血性卒中发生之间的关联。
在CHS的白人参与者中，74个SNP中的7个（位于HPS1、ITGAE、ABCG2、MYH15、FSTL4、CALM1和BAT2基因中）预先确定的风险等位基因与卒中风险增加呈名义上的关联（单侧P<0.05，错误发现率=0.42）。在黑人参与者中，5个SNP（位于KRT4、LY6G5B、EDG1、DMXL2和ABCG2基因中）预先确定的风险等位基因与卒中呈名义上的关联（单侧P<0.05,错误发现率=0.55）。ABCG2基因中的Val12Met SNP在CHS的白人（风险比，1.46；90%CI，1.05至2.03）和黑人（风险比，3.59；90%CI，1.11至11.6）参与者中均与卒中相关。在CHS的白人（10%对6%）和黑人（12%对3%）参与者中，Val等位基因纯合子的卒中10年累积发病率的Kaplan-Meier估计值均高于Met等位基因携带者。
ABCG2基因中的Val12Met SNP（编码一种固醇和外源性物质转运蛋白）与CHS的白人和黑人参与者的缺血性卒中发生相关。
