Sonoda A, Murata M, Ito D, Tanahashi N, Ohta A, Tada Y, Takeshita E, Yoshida T, Saito I, Yamamoto M, Ikeda Y, Fukuuchi Y, Watanabe K
Departments of Laboratory Medicine, School of Medicine, Keio University, Tokyo, Japan.
Stroke. 2000 Feb;31(2):493-7. doi: 10.1161/01.str.31.2.493.
Platelets play pivotal roles in the development of ischemic cerebrovascular disease (CVD). The platelet glycoprotein (GP) Ib/IX/V complex is a receptor for von Willebrand factor, which plays a major role in the initial phase of platelet activation under high shear stress conditions. This study was designed to investigate the association between a genetic variation of this receptor and the prevalence of CVD.
Two hundred patients with ischemic CVD, as confirmed by brain CT and/or MRI, and 317 age- and sex-matched control subjects without clinical evidence of CVD or cardiovascular disease were analyzed for their genotype frequencies of the (145)Thr/Met dimorphism of the alpha-chain of GPIb (GPIbalpha).
Genotypes with (145)Met (T/M and M/M) were more frequently found in the CVD patients (26.5%) than in control subjects (14.2%, P=0.0005). The genotype effect was more obvious in those <60 years of age or without acquired cardiovascular risk factors. The odds ratio for nonsmoking women <60 years of age was 10. 6 (95% confidence intervals, 2.2 to 51.7). Although the number of patients studied was small (n=24), transient ischemic attack showed the highest odds ratio (4.3, P=0.0004), followed by lacunar infarction (OR=2.2, P=0.0024) and atherothrombotic infarction (OR=1. 5, P=0.3143). Logistic regression analysis revealed that the presence of Met-allele was independently associated with CVD.
Our study suggests that the platelet GPIbalpha genotype is a genetic risk factor for ischemic CVD.
血小板在缺血性脑血管疾病(CVD)的发生发展中起关键作用。血小板糖蛋白(GP)Ib/IX/V复合物是血管性血友病因子的受体,在高剪切应力条件下血小板激活的初始阶段起主要作用。本研究旨在探讨该受体基因变异与CVD患病率之间的关联。
对200例经脑CT和/或MRI证实的缺血性CVD患者以及317例年龄和性别匹配、无CVD或心血管疾病临床证据的对照者,分析其血小板糖蛋白Ibα链(GPIbalpha)第145位苏氨酸/蛋氨酸二态性的基因型频率。
CVD患者中携带(145)蛋氨酸(T/M和M/M)基因型的频率(26.5%)高于对照者(14.2%,P = 0.0005)。基因型效应在年龄<60岁或无后天性心血管危险因素的人群中更为明显。<60岁的非吸烟女性的优势比为10.6(95%置信区间,2.2至51.7)。尽管研究的患者数量较少(n = 24),短暂性脑缺血发作的优势比最高(4.3,P = 0.0004),其次是腔隙性梗死(OR = 2.2,P =