Thrombosis Gene Polymorphisms and Early CHD Risk in HERS

描述(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 观察到患冠心病(CHD)的风险短暂增加 激素替代治疗(HRT)开始后的事件。一些证据 这表明激素替代疗法的这种不良影响可能仅限于一小部分女性。 他们是雌激素治疗血栓并发症的独一无二的风险。 在其产物调节的基因中有几个描述得很好的多态 凝血或纤溶作用可能增加血栓形成的风险 雌激素疗法的最新进展。这些多态包括凝血因子V莱顿、凝血酶原 20210A，因子VII R353Q。纤溶酶原激活物抑制物-1(PAI-1)4G/5G， 纤维蛋白原B-β-455A和血小板膜糖蛋白GPⅢa P1-A1.A2。我们提出一个嵌套的 361例冠心病或静脉血栓形成患者的病例对照研究 事件(VTE)(n=95)和两个临床配对的对照组以评估这种关系 上述基因多态、HRT与CHD或VTES发病风险之间的关系。我们会 估计患有和不患有HRT的妇女中HRT的绝对和相对风险 6个候选血栓形成基因的多态性和一种基因型的证据检验 *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，评估甘油三酯对与以下疾病相关的风险的影响 凝血因子VII和纤溶酶原激活物-1的多态性，并探讨组合的影响 风险的多态。该项目的DNA将从中央获取 试验期间收集的巴氏涂片。 如果该项目揭示了基于血栓形成基因的高危亚组 多态，女性可以进行这种情况的筛查，并警告不要 使用激素替代疗法。相反，低风险女性可能会在 追求各种健康益处，包括可能降低冠心病风险。 因此，该项目可能会导致更有效的战略，以预防冠心病 妇女，提高HRT的安全性，并增加不断扩大的知识体系 关于药物/基因相互作用，因为它们与治疗和预防 疾病。

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.