Biostatistics Unit, Mayo Clinic, Jacksonville, FL 32224, USA.
Eur J Neurol. 2013 Feb;20(2):300-8. doi: 10.1111/j.1468-1331.2012.03846.x. Epub 2012 Aug 6.
Ischaemic stroke shares common traditional risk factors with coronary artery disease (CAD) and myocardial infarction (MI). This study evaluated whether genetic risk factors for CAD and MI also affect susceptibility to ischaemic stroke in Caucasians and African Americans.
Included in the study were a Caucasian series (713 ischaemic stroke patients, 708 controls) and a small African American series (166 ischaemic stroke patients, 117 controls). Twenty single-nucleotide polymorphisms (SNPs) previously shown to be associated with CAD or MI were genotyped and assessed for association with ischaemic stroke and ischaemic stroke subtypes using odds ratios (ORs) from multivariable logistic regression models.
In Caucasians, four SNPs on chromosome 9p21 were significantly associated with risk of cardioembolic stroke, the strongest of which was rs1333040 (OR 1.55, P = 0.0007); similar but weaker trends were observed for small vessel stroke, with no associations observed regarding large vessel stroke. Chromosome 9p21 SNPs were also associated with risk of ischaemic stroke in African Americans (rs1333040, OR 0.65, P = 0.023; rs1333042, OR 0.55, P = 0.070; rs2383207, OR 0.55, P = 0.070). The PSMA6 SNP rs1048990 on chromosome 14q13 was associated with overall ischaemic stroke in both Caucasians (OR 0.80, P = 0.036) and African Americans (OR 0.31, P = 0.020).
Our results provide evidence that chromosome 9p21 variants are associated with cardioembolic ischaemic stroke in Caucasians and with overall ischaemic stroke in African Americans. The PSMA6 variant rs1048990 also appears to affect susceptibility to ischaemic stroke in both populations. These findings require validation, particularly the preliminary findings regarding African Americans given the small size of that series.
缺血性脑卒中与冠状动脉疾病（CAD）和心肌梗死（MI）具有共同的传统危险因素。本研究评估了 CAD 和 MI 的遗传危险因素是否也会影响白种人和非裔美国人发生缺血性脑卒中的易感性。
本研究纳入了一个白种人系列（713 例缺血性脑卒中患者，708 例对照）和一个非裔美国人小系列（166 例缺血性脑卒中患者，117 例对照）。先前已证明与 CAD 或 MI 相关的 20 个单核苷酸多态性（SNP）进行了基因分型，并使用多变量逻辑回归模型的比值比（OR）评估了它们与缺血性脑卒中及缺血性脑卒中亚型的相关性。
在白种人中，9p21 染色体上的 4 个 SNP 与心源性栓塞性脑卒中风险显著相关，其中最强的 SNP 是 rs1333040（OR 1.55，P = 0.0007）；小血管性脑卒中也存在类似但较弱的趋势，而大动脉性脑卒中则无相关性。9p21 染色体 SNP 也与非裔美国人的缺血性脑卒中风险相关（rs1333040，OR 0.65，P = 0.023；rs1333042，OR 0.55，P = 0.070；rs2383207，OR 0.55，P = 0.070）。染色体 14q13 上的 PSMA6 SNP rs1048990 与白种人（OR 0.80，P = 0.036）和非裔美国人（OR 0.31，P = 0.020）的总体缺血性脑卒中均相关。
我们的研究结果提供了证据，表明 9p21 染色体变异与白种人心源性栓塞性缺血性脑卒中以及非裔美国人的总体缺血性脑卒中相关。PSMA6 变异 rs1048990 似乎也会影响两个人群发生缺血性脑卒中的易感性。这些发现需要进一步验证，特别是关于非裔美国人的初步发现，因为该系列的规模较小。
