Inflammation Genomics and Atherosclerosis

炎症基因组学和动脉粥样硬化

• 批准号: 6534706
• 负责人: DAVID Stuart SISCOVICK
• 金额: $ 58.56万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-16 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6534706
• 关键词: African American; DNA; acute phase protein; atherosclerosis; body physical activity; calcification; cardiovascular disorder epidemiology; caucasian American; clinical research; coronary artery; coronary disorder; disease /disorder onset; fibrinogen; functional /structural genomics; gene environment interaction; gene interaction; genetic polymorphism; genetic susceptibility; genotype; human data; human genetic material tag; human middle age (35-64); human population genetics; inflammation; obesity; racial /ethnic difference; smoking; thrombosis

DESCRIPTION (provided by applicant): Advances in biology suggest that atherosclerosis may reflect, in part, the vascular consequences of chronic inflammation. Using information on complete sequence variation and common haplotypes on a set of candidate genes generated through the NHLBI Program in Genomic Applications (PGA) at the University of Washington, we propose to examine the associations of common variation in inflammation/thrombosis genes with intermediate quantitative phenotypes and subclinical coronary atherosclerosis in the Coronary Artery Risk Factor Development in Young Adult (CARDIA) Study, a large, bi-racial cohort study. The set of 25 candidate genes involve pathways (cytokines, chemokines, and their receptors; cellular adhesion molecules; and, coagulation proteins) and include several receptor-ligand pairs. Using cladistic analysis and the resources of the PGA, we will identify a limited set of single nucleotide polymorphisms (range 3-10 SNPs per gene) that characterize common haplotypes in these candidate genes within persons of African descent and European descent. DNA from the CARDIA Year 10 examination (n = 3,950 subjects) will be genotyped for the selected variants that characterize the common haplotypes. Data on the presence of common variants and haplotypes will be incorporated into the CARDIA Study database. Levels of two important intermediate phenotypes, fibrinogen and C-reactive protein (CRP) were previously determined. Non-invasive assessment of coronary atherosclerosis, defined as the presence of coronary artery calcification (CAC), was obtained on CARDIA participants at the Year 15 exam. Analyses will be stratified by race/ethnicity and focus on the associations of the common haplotypes with fibrinogen, CRP, and CAC measured in early adult life. Secondarily, we will explore possible gene-gene and gene-environment interactions. The proposed multi-disciplinary collaboration should enhance the sensitivity and specificity of efforts to assess the associations of common variation in sets of inflammation/thrombosis candidate genes and cardiovascular risk in young adults.

描述（由申请人提供）：生物学的进展表明，动脉粥样硬化可能部分反映了慢性炎症的血管后果。使用有关通过NHLBI计划在华盛顿大学通过NHLBI计划（PGA）产生的一组候选基因的完全序列变化和常见的单倍型的信息，我们建议研究炎症/血栓形成基因与中间定量表型和亚细胞核心菌群的炎症/血栓形成基因在炎症/血栓形成基因中的共同变化的关联（大型，双种族人队列研究。一组25个候选基因涉及途径（细胞因子，趋化因子及其受体；细胞粘附分子；和，凝结蛋白），并包括几种受体配体对。使用Cladistic分析和PGA的资源，我们将确定一组有限的单核苷酸多态性（每个基因3-10个SNP范围3-10个SNP），这些核苷酸是在非洲血统和欧洲血统中这些候选基因中常见的单倍型的表征。 Cardia 10年级检查中的DNA（n = 3,950名受试者）将针对表征常见单倍型的选定变体进行基因分型。有关存在常见变体和单倍型的存在的数据将纳入Cardia研究数据库。先前确定了两种重要的中间表型，纤维蛋白原和C反应蛋白（CRP）的水平。在15年级考试中，在Cardia参与者上获得了冠状动脉粥样硬化的非侵入性评估，该评估被定义为冠状动脉钙化（CAC）。分析将根据种族/种族分析，并将重点放在成年早期生命早期测量的纤维蛋白原，CRP和CAC的共同关联上。其次，我们将探索可能的基因基因和基因环境相互作用。拟议的多学科合作应提高努力的敏感性和特异性，以评估炎症/血栓形成候选基因和年轻人心血管风险的共同变异的关联。