Thrombosis Gene Polymorphisms and Early CHD Risk in HERS

HERS 中的血栓形成基因多态性和早期 CHD 风险

• 批准号: 6422151
• 负责人: DAVID McLeod HERRINGTON
• 金额: $ 33.58万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6422151
• 关键词: cardiovascular disorder risk; coronary disorder; drug interactions; estrogens; female; fibrinogen; gene environment interaction; genetic polymorphism; genetic screening; genetic susceptibility; genotype; glycoproteins; hormone therapy; human tissue; iatrogenic disease; myocardial infarction; patient oriented research; plasminogen activator inhibitors; platelets; point mutation; postmenopause; progestins; protein C; prothrombin; triglycerides; venous thrombosis; women's health

DESCRIPTION (provided by applicant): The Heart and Estrogen/progestin Replacement Study (HERS) and several other clinical studies and clinical trials have observed a transient increase in risk for coronary heart disease (CHD) events after initiation of hormone replacement therapy (HRT). Some evidence suggests that this adverse effect of HRT may be limited to a subgroup of women who are uniquely at risk for a thrombotic complication of estrogen therapy. There are several well-described polymorphisms in genes whose products regulate coagulation or fibrinolysis that could augment thrombotic risk in the setting of estrogen therapy. These polymorphisms include Factor V Leiden, prothrombin 20210A, Factor VII R353Q. plasminogen activator inhibitor-1 (PAI-1) 4G/5G, fibrinogen B-beta-455A, and platelet GP IIIa P1-A1.A2. We propose a nested case-control study among HERS women with CHD (n = 361) or venous thrombotic events (VTEs) (n = 95) and two clinic-matched controls to assess the relation between the above listed polymorphisms, HRT, and risk for CHD or VTEs. We will estimate the absolute and relative risk of HRT among women with and without the six candidate thrombosis gene polymorphisms and test for evidence of a genotype * HRT interaction. In secondary analyses, we will focus on events that occurred in the first year, evaluate the effect of triglycerides on risk associated with the Factor VII and PAI-1 polymorphisms, and explore the impact of combinations of polymorphisms on risk. DNA for this project will be acquired from centrally stored Pap smears that were collected during the trial. If this project reveals a high-risk subgroup based on thrombosis gene polymorphisms, women could be screened for this condition and cautioned not to use HRT. Conversely, low-risk women might be able to use HRT more safely in pursuit of various health benefits, including a possible reduction in CHD risk. Thus, this project may lead to more effective strategies to prevent CHD in women, enhance the safety of HRT, and add to the expanding body of knowledge concerning drug/gene interactions as they relate to treatment and prevention of disease.

描述（由申请人提供）：心脏和雌激素/孕激素 替代研究（HERS）和其他几项临床研究和临床试验 观察到冠心病 (CHD) 风险短暂增加 开始激素替代疗法（HRT）后发生的事件。一些证据 表明 HRT 的这种不利影响可能仅限于女性亚群 那些特别有雌激素治疗血栓并发症风险的人。 基因中有几个已被充分描述的多态性，其产物调节 凝血或纤维蛋白溶解可能会增加该环境中的血栓形成风险 雌激素治疗。这些多态性包括因子 V Leiden、凝血酶原 20210A，因子 VII R353Q。纤溶酶原激活剂抑制剂-1 (PAI-1) 4G/5G， 纤维蛋白原 B-β-455A 和血小板 GP IIIa P1-A1.A2。我们提出一个嵌套的 患有 CHD (n = 361) 或静脉血栓形成的 HERS 女性的病例对照研究 事件 (VTE) (n = 95) 和两个临床匹配对照来评估关系 上述列出的多态性、HRT 和 CHD 或 VTE 风险之间的关系。我们将 估计有或没有激素替代疗法的女性的绝对和相对风险 六种候选血栓基因多态性并测试基因型证据 * HRT 相互作用。在二次分析中，我们将重点关注发生的事件 在第一年，评估甘油三酯对相关风险的影响 因子 VII 和 PAI-1 多态性，并探讨组合的影响 多态性对风险的影响。该项目的 DNA 将从中央获取 储存试验期间收集的巴氏涂片。 如果这个项目根据血栓基因揭示了一个高危亚组 多态性，可以对女性进行这种情况的筛查，并警告不要这样做 使用激素替代疗法。相反，低风险女性可能能够更安全地使用 HRT 追求各种健康益处，包括可能降低冠心病风险。 因此，该项目可能会产生更有效的策略来预防冠心病 女性，提高 HRT 的安全性，并丰富知识体系 关于药物/基因相互作用，因为它们与治疗和预防有关 疾病。