Matarin Mar, Brown W Mark, Hardy John A, Rich Stephen S, Singleton Andrew B, Brown Robert D, Brott Thomas G, Worrall Bradford B, Meschia James F
Neurogenetics Laboratory, National Institute on Aging, Bethesda, Maryland, USA.
J Cereb Blood Flow Metab. 2008 Jan;28(1):81-9. doi: 10.1038/sj.jcbfm.9600508. Epub 2007 May 30.
Genetic variants in the gene encoding integrin alpha2 (ITGA2) have been reported to be associated with an increased risk for ischemic stroke. The purpose of this study was to investigate the association between haplotype-tagging single-nucleotide polymorphisms (tSNPs) in ITGA2 and risk of ischemic stroke in a collection of North American stroke cases and controls. The study included 484 cases and 263 controls. Thirteen tSNPs were genotyped. Association tests at and across each tSNP were performed, including haplotype association analysis. Secondary analyses considered stroke subtypes on the basis of Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. We observed significant association between tSNP rs3756541 (additive model, odds ratio (OR), 1.49; 95% confidence interval (CI), 1.11 to 2.04; P=0.009) and disease and a trend toward association at rs2303124 (recessive model, OR, 1.56; 95% CI, 1.05 to 2.33; P=0.03). These associations remained significant in the haplotype analyses. The associated tSNPs did not distinguish stroke etiology after application of TOAST criteria. Our results suggest that genetic variability within ITGA2 may confer risk for ischemic stroke independent of conventional risk factors. These results provide additional support for a role for platelet receptor genes in the pathogenesis of ischemic stroke of diverse subtypes.
据报道，编码整联蛋白α2（ITGA2）的基因中的遗传变异与缺血性中风风险增加有关。本研究的目的是在一组北美中风病例和对照中，调查ITGA2中单体型标签单核苷酸多态性（tSNP）与缺血性中风风险之间的关联。该研究纳入了484例病例和263例对照。对13个tSNP进行了基因分型。对每个tSNP及其之间进行了关联测试，包括单倍型关联分析。二级分析根据急性中风治疗中组织纤溶酶原激活剂10172试验（TOAST）标准考虑中风亚型。我们观察到tSNP rs3756541与疾病之间存在显著关联（加性模型，优势比（OR）为1.49；95%置信区间（CI）为1.11至2.04；P = 0.009），rs2303124存在关联趋势（隐性模型，OR为1.56；95%CI为1.05至2.33；P = 0.03）。这些关联在单倍型分析中仍然显著。应用TOAST标准后，相关的tSNP无法区分中风病因。我们的结果表明，ITGA2内的遗传变异可能独立于传统风险因素赋予缺血性中风风险。这些结果为血小板受体基因在不同亚型缺血性中风发病机制中的作用提供了额外支持。
