Clotting Genetic Variants, Hormones, and Venous Thrombosis
研究概览
详细说明
BACKGROUND:
Venous thromboembolism (VTE) occurs commonly in adults and risk increases 3-fold among users of hormone replacement therapy (HRT), oral contraceptives (OC), and selective estrogen receptor modulators (SERMs). Epidemiologic data suggest that genetic variation in the pro-coagulant, anti-coagulant, and fibrinolytic pathways may modify the risk of VTE in women, especially in the presence of hormone use. The primary aim of this study is to identify genetic variants in 12 key clotting proteins that may modify the risk of VTE independently, through gene-gene interactions, and in the presence of HRT, OC, or SERM use. Proteins include thrombomodulin, protein C, endothelial protein C receptor, protein S, antithrombin III, tissue activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (TPA), and factors VIII, IX, X, and XlII A and B. Secondary aims are to determine if levels of TAFI antigen, TPA antigen, activated protein C resistance, and D-dimer serve as intermediate phenotypes for gene-drug interactions and VTE risk. The setting for this study is Group Health Cooperative (GHC) of Puget Sound, a health maintenance organization in the Pacific Northwest. This study is part of an on going, case-control study addressing the effects of genetic variants on drug safety, particularly cardiovascular endpoints.
DESIGN NARRATIVE:
The primary aim of this case-control study is to identify genetic variants in 12 key blood clotting proteins that may modify the risk of venous thromboembolism independently, through gene-gene interactions, and in the presence of hormone replacement therapy, oral contraceptives, or selective estrogen receptor modulators use. Proteins include thrombomodulin, protein C, endothelial protein C receptor, protein S, antithrombin III, tissue activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (TPA), and factors VIII, IX, X, and XlII A and B. Secondary aims of the study are to determine if levels of TAFI antigen, TPA antigen, activated protein C resistance, and D-dimer serve as intermediate phenotypes for gene-drug interactions and VTE risk. The setting for this study is the Group Health Cooperative (GHC) of Puget Sound, a health maintenance organization in the Pacific Northwest. This study is part of an on going, case-control study addressing the effects of genetic variants on drug safety, particularly cardiovascular endpoints.
All inpatient and outpatient VTE events occurring between 1/1/1995 and 12/31/2007 among women 18 to 89 years of age will be eligible for this study. Controls will be a random selection of women from GHC matched on age, hypertension status, and calendar year. Medical records will be reviewed to determine study eligibility and to collect V'i'E risk factor information. Hormone and SERM use will be ascertained from the GHC pharmacy database. Phlebotomy will be performed on surviving cases and controls to collect plasma samples and genetic information. Logistic regression analyses will determine which haplotypes of key elements in the clotting pathways modify the association between hormones or SERMSs and VTE risk. The identification of common genetic variants that either increase or decrease VTE risk independently or in the presence of hormone or SERMs will help to inform clinicians and their female patients about the personal safety of hormone use.
The Seattle Program for Genomics Applications (PGA) will identify single nucleotide polymorphisms (SNPs) in the 12 candidate genes and use linkage disequilibrium to generate haplotypes. A group at the Leiden University Medical Center will perform the genotyping of the study population.
研究类型
注册 (实际的)
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
学习计划
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
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General
No intervention
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Venous Thrombosis
大体时间:Retrospective
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Incidence of venous thrombosis
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Retrospective
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合作者和调查者
调查人员
- 学习椅:Nicholas Smith、University of Washington
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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