Individual Propensity to Venous Thrombosis

静脉血栓形成的个体倾向

• 批准号: 7326839
• 负责人: John A. Heit
• 金额: $ 75.4万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7326839
• 关键词: Acute; Age; Allegra; Anticardiolipin Antibodies; Anticoagulants; Arizona; Arts; Bathing; Biological Assay; Budgets; Candidate Disease Gene; Capillary Electrophoresis; Carbon Dioxide; Cardiovascular Diseases; Caring; Cells; Chairperson; Client; Clinic; Clinical; Clinical Medicine; Coagulation Process; Comb animal structure; Complex; Computer software; Computers; Consultations; Core Facility; Core Protein; Correlative Study; County; Data; Department of Defense; Detection; Development; Diagnostic; Disease; Doctor of Medicine; Doctor of Philosophy; Education; Educational process of instructing; Electron Spin Resonance Spectroscopy; Electrophoresis; Equilibrium; Equipment; Extramural Activities; Faculty; Floor; Florida; Fluorescence; Fluorescence Microscopy; Foundations; Freeze Drying; Freezing; Frequencies; Funding; Funding Agency; Gamma counter; Gases; Gender; Genes; Genetic; Genotype; Goals; Grant; Growth and Development function; Haplotypes; Health; Hematology; Hematopathology; Hemophilia A; Hemorrhage; Hemostatic function; Hospitals; Incidence; Incubators; Individual; Industry; Inflammation; Institution; Internal Medicine; Investigation; Isoelectric Focusing; Joints; Kinetics; Laboratories; Laboratory Research; Lead; Leadership; Light Microscope; Liquid substance; Lupus; Mails; Malignant Neoplasms; Medical; Medical Research; Medical center; Medicine; Methodist Church; Methods; Microcomputers; Microscope; Minnesota; Modeling; Molecular; Molecular Biology; Molecular Genetics; Monitor; Mus; N.I.H. Research Support; New Brunswick; Nitrogen; Oligonucleotide Primers; Operative Surgical Procedures; Pathology; Pathway interactions; Patients; Pediatric Hematology/Oncology; Peptide Mapping; Phase; Platelet Count measurement; Polymerase Chain Reaction; Power Sources; Prophylactic treatment; Protein Biosynthesis; Protein Chemistry; Proteins; Purpose; Range; Reader; Research; Research Infrastructure; Research Personnel; Research Training; Resources; Risk Factors; Safety; Sampling; Schools; Science; Scientist; Sepharose; Solid; Source; Specimen; Speed; Sterility; Subway; Sudden Death; Support of Research; Susceptibility Gene; System; Systems Analysis; Telephone; Testing; Thromboembolism; Thrombophilia; Thrombosis; Time; United States; United States National Institutes of Health; Vacuum Pumps; Variant; Venous; Venous Thrombosis; Wages; Walking; Water; Whole Blood; Work; base; cost; cryostat; factor V Leiden; foot; gel electrophoresis; gene interaction; improved; instrument; interest; liquid crystal polymer; medical schools; microwave electromagnetic radiation; monoclonal antibody production; paragon; pressure; programs; quality assurance; residence; school health; sensor; tissue culture; treatment center; treatment fees

Our overall long-term goal is to determine risk factors for the complex (multifactorial) disease, venous thromboembolism (VTE). We will examine both candidate genes and circulating procoagulant activity to determine if they are associated with VTE. Our specific aims are: Aim 1: To identify functional SNPs/ht- SNPs within a large set candidate genes and test these SNPs/ht-SNPs for an association with VTE. Using high throughput genotyping of known gene-centric DMAvariants (n=5000), we will test a large set of candidate genes (n=300) within the anticoagulant, procoagulant, fibrinolytic, and acute systemic inflammation pathways. Linkage dysequilibrium will be used to identify haplotype-tagging SNPs within 1,500 clinic-based, idiopathic VTE cases from the Midwest, and 1500 unrelated controls frequency-matched on patient age, gender, and county of residence; Aim 2: To determine if complex candidate gene interactions are associated with VTE. Using data from aim 1, we will apply single SNP and haplotype analyses to identify specific variants and groups of variants associated with VTE. We will also investigate the joint effects of these susceptibility genes on VTE stratified on Factor V Leiden; and Aim 3: To determine if functional assays of circulating whole blood procoagulant activity associate with VTE, including genetic interactions. We will use global functional assays to prospectively test such activity for an association with VTE in a sample of our clinic-based VTE cases (n=300) and controls (n=600), including genetic interactions. VTE is a major national health problem, with over 275,000 incident cases per year in the United States and costing over $7.3 billion (in 1999 dollars) per year for treatment charges alone. Since one-quarter of PE patients present as sudden death, the incidence of VTE must be reduced in order to improve survival. However, the incidence of VTE has remained relatively constant at about 1 per 1000 since 1980. Clearly, better methods of targeting VTE prophylaxis are needed.

我们的总体长期目标是确定复杂（多因素）疾病的风险因素， 血栓栓塞（VTE）。我们将检查候选基因和循环促凝血活性， 确定它们是否与VTE相关。我们的具体目标是：目标1：鉴定功能性SNPs/ht- 在一个大的候选基因集内的SNPs，并测试这些SNPs/ht-SNPs与VTE的关联。使用 为了对已知的以基因为中心的DMA变体进行高通量基因分型（n=5000），我们将测试一大组 候选基因（n=300）在抗凝剂，促凝血，纤溶，急性全身 炎症通路。连锁不平衡将用于在1，500个SNP中识别单倍型标记SNP。 来自中西部的基于诊所的特发性静脉血栓栓塞病例和1500名不相关的对照，频率匹配 患者年龄、性别和居住县;目的2：确定复杂的候选基因相互作用 与VTE有关。利用目标1的数据，我们将应用单核苷酸多态性和单体型分析来识别 与静脉血栓栓塞相关的特定变体和变体组。我们还将研究以下因素的联合影响： 这些VTE易感基因按因子V Leiden分层;目的3：确定功能性 与VTE相关的循环全血促凝血活性测定，包括遗传相互作用。 我们将使用全局功能测定来前瞻性地检测这种活性与VTE的相关性， 我们的基于临床的VTE病例（n=300）和对照组（n=600）的样本，包括遗传相互作用。VTE包括 这是一个重大的国家健康问题，在美国每年有超过275，000起事件， 每年仅治疗费用就超过73亿美元（按1999年美元计算）。因为四分之一的PE患者 由于静脉血栓栓塞症通常表现为猝死，因此必须降低静脉血栓栓塞症的发生率以提高生存率。但 自1980年以来，静脉血栓栓塞的发病率相对稳定，约为1/1000。显然，更好的方法 有针对性的预防静脉血栓栓塞是必要的。