Individual Propensity to Venous Thrombosis

静脉血栓形成的个体倾向

• 批准号: 7168799
• 负责人: John A. Heit
• 金额: $ 75.87万
• 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/7168799
• 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; Linkage Disequilibrium; 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

DESCRIPTION (provided by applicant): 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 DMA variants (n=5000), we will test a large set of candidate genes (n=300) within the anticoagulant, procoagulant, fibrinolytic, and acute systemic inflammation pathways. Linkage disequilibrium 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.

描述（由申请人提供）：我们的总体长期目标是确定复杂（多因素）疾病，静脉血栓栓塞（VTE）的危险因素。我们将检查候选基因和循环凝胶活性，以确定它们是否与VTE相关。我们的具体目的是：目标1：在大型候选基因中识别功能性SNP/HT-SNP，并测试这些SNP/HT-SNP与VTE的关联。使用已知基因为中心DMA变异的高吞吐量基因分型（n = 5000），我们将在抗凝剂，proc凝，纤维蛋白和急性全身性炎症途径中测试大量候选基因（n = 300）。连锁不平衡将用于识别中西部1,500个基于诊所的特发性VTE病例中的单倍型标签SNP，以及1500个对患者年龄，性别和居住县的频率频率频率的不相关控制；目标2：确定复杂的候选基因相互作用是否与VTE相关。使用来自AIM 1的数据，我们将应用单个SNP和单倍型分析来识别与VTE相关的特定变体和变体组。我们还将研究这些敏感性基因对莱顿因子VTE的关节作用；和目标3：确定是否与VTE相关的循环全血凝性活性的功能测定，包括遗传相互作用。我们将使用全球功能测定法在基于诊所的VTE病例（n = 300）和对照组（n = 600）（包括遗传相互作用）的样本中使用全局功能测定与VTE相关性。 VTE是一个重大的国家健康问题，在美国，每年有超过275,000例事件案件，仅每年耗资超过73亿美元（以1999年的美元）进行治疗费用。由于四分之一的PE患者作为猝死，因此必须降低VTE的发病率以提高生存率。然而，自1980年以来，VTE的发生率一直保持相对恒定。显然，需要更好的靶向VTE预防方法。