Fibrinolytic gene polymorphism and ischemic stroke
Fibrinolytic gene polymorphism and ischemic stroke
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DOI：
10.1161/01.str.0000183617.54752.69
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发表时间：
2005-10-01
期刊：
影响因子：
8.3
通讯作者：
Jern, C
中科院分区：
文献类型：
--
作者：
Jood, K;Ladenvall, P;Jern, C
背景和目的 - 组织型纤溶酶原激活剂 (tPA) -7351C > T 和纤溶酶原激活剂抑制剂 1 型 (PAI-1) - 675 4G > 5G 多态性影响转录活性。这两种变异均与心肌梗塞相关，T 和 4G 等位基因的风险分别增加。在这项研究中，我们调查了这些多态性、各自的血浆蛋白水平和缺血性中风之间可能的关联。 方法 - 在萨尔格伦斯卡学院缺血性中风研究 (SAHLSIS) 中，招募了 600 名 18 至 69 岁的急性缺血性中风患者和 600 名匹配的社区对照。使用急性治疗标准中的 Org 10172 试验确定中风亚型。结果 - 个体遗传变异与缺血性中风之间没有关联。 tPA T 等位基因携带者总体缺血性卒中的多变量调整优势比为 1.11（95% CI 0.87 至 1.43），PAI-1 4G 等位基因纯合子受试者为 0.84（95% CI 0.64 至 1.11）。当基因型组合时，观察到 tPA CC/PAI-1 4G4G 基因型组合的保护作用（比值比 0.65，95% CI 0.43 至 0.98；P < 0.05）。随访时血浆 tPA 和 PAI-1 抗原水平与总体缺血性卒中独立相关。 tPA 抗原因中风亚型而异，在大血管疾病和心源性中风患者中最高。结论 - tPA -7351C > T 和 PAI-1 至 675 4G > 5G 多态性均未显示与缺血性中风存在显着相关性。对于 tPA CC/PAI-1 4G4G 基因型组合，观察到保护作用。总的来说，这些结果与 tPA 和 PAI-1 在大脑中比心脏中更复杂的作用一致。
Background and Purpose - The tissue-type plasminogen activator (tPA) -7351C > T and the plasminogen activator inhibitor type 1 (PAI- 1) - 675 4G > 5G polymorphisms influence transcriptional activity. Both variants have been associated with myocardial infarction, with increased risk for the T and 4G allele, respectively. In this study we investigated the possible association between these polymorphisms, the respective plasma protein levels, and ischemic stroke.Methods - In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), 600 patients with acute ischemic stroke aged 18 to 69 years and 600 matched community controls were recruited. Stroke subtype was determined using Trial of Org 10172 in Acute Treatment criteria.Results - There were no associations between individual genetic variants and ischemic stroke. The multivariate-adjusted odds ratio for overall ischemic stroke was 1.11 (95% CI 0.87 to 1.43) for tPA T allele carriers, and 0.84 (95% CI, 0.64 to 1.11) for subjects homozygous for the PAI-1 4G allele. When genotypes were combined, a protective effect for the tPA CC/ PAI-1 4G4G genotype combination was observed (odds ratio 0.65, 95% CI 0.43 to 0.98; P < 0.05). Plasma levels of tPA and PAI-1 antigen at follow-up were independently associated with overall ischemic stroke. tPA-antigen differed by stroke subtype and was highest among those with large-vessel disease and cardioembolic stroke.Conclusions - Neither the tPA -7351C > T nor the PAI-1 to 675 4G > 5G polymorphism showed significant association with ischemic stroke. For the tPA CC/ PAI-1 4G4G genotype combination, a protective effect was observed. Collectively, these results are consistent with a more complex role for tPA and PAI-1 in the brain as compared with the heart.