Meschia James F, Brott Thomas G, Brown Robert D, Crook Richard J P, Frankel Michael, Hardy John, Merino José G, Rich Stephen S, Silliman Scott, Worrall Bradford Burke
Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
BMC Neurol. 2003 Jul 8;3:4. doi: 10.1186/1471-2377-3-4.
The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype.
METHODS/DESIGN: The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes beta-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future.
The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes.
缺血性中风遗传风险的分子基础可能是多基因的，并受环境因素影响。几项小型病例对照研究表明，缺血性中风与编码凝血级联蛋白和血小板受体的基因多态性之间存在关联。我们的目的是研究止血基因多态性与缺血性中风之间的潜在关联，尤其着重于对表型进行详细特征描述。
方法/设计：缺血性中风遗传研究是一项针对近期首次发生缺血性中风且经计算机断层扫描或磁共振成像确诊的成年人的前瞻性多中心遗传关联研究。患者在美国的学术医疗中心接受评估，并与性别和年龄匹配的对照组进行比较。中风亚型通过使用标准化、经过验证的机制和综合征分类系统进行中心盲法判定。要检测多态性的基因 panel 包括β-纤维蛋白原以及血小板糖蛋白 Ia、Iba 和 IIb/IIIa。创建永生化细胞系以便未来能高效且经济地检测其他候选基因。
该研究旨在尽量减少生存偏差，并允许探索特定多态性与缺血性中风各个亚型之间的关联。数据集还将允许对中风预后的遗传决定因素进行研究。拥有细胞系将允许对未来的候选风险因素基因进行检测。
