Genetic Determinants of Subclinical Carotid Disease

亚临床颈动脉疾病的遗传决定因素

• 批准号: 7001317
• 负责人: Tatjana Rundek
• 金额: $ 29.54万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7001317
• 关键词: African American; Hispanic Americans; angiocardioultrasonography; blood pressure; blood vessel disorder; cardiovascular disorder epidemiology; cardiovascular disorder risk; carotid artery; caucasian American; clinical research; diet; gender difference; gene environment interaction; genetic susceptibility; genotype; human subject; inflammation; linkage mapping; lipid metabolism; longitudinal human study; nutrition related tag; racial /ethnic difference; saturated fat; single nucleotide polymorphism; smooth muscle; statistics /biometry; vascular resistance

DESCRIPTION (provided by applicant): Carotid artery intima-media thickness (IMT) and distensibility represent structural and functional subclinical carotid disease, respectively. They can be measured by ultrasound, and can be used as intermediate phenotypes for clinical stroke/cardiovascular events. Studies have shown that increased carotid IMT or decreased distensibility are independent risk factors for myocardial infarction and stroke. Furthermore, family studies reported that appreciable heritability in both intermediate phenotypes, which indicates strong genetic influence on the development of carotid thickness and stiffness. These findings warrant the endeavor to map genetic markers to these two phenotypes. The main goal of this research is to study the genetic polymorphisms associated with carotid IMT and distensibility in the three race/ethnic groups (whites, blacks and Hispanics) from the Northern Manhattan Study (NOMAS) cohort. The strengths of the current application include: 1) both phenotypic data have been measured in a large cohort (n about 1500); 2) the cohort includes three race/ethnic groups, which provides an invaluable data source to compare genetic effect across three major race/ethnic groups in the USA; 3) new technologies in molecular genetics, comparative genomics and statistical genetics will be employed in our studies, and 4) the NOMAS Family Study has been supported by the NIH, which will allow us to evaluate the genetic effect on IMT and distensibility by linkage analysis. Therefore, the results from the current application can be validated from a different study design and analytic approach. The development of IMT and distensibility may involve lipid metabolism, molecule adhesion, endothelial function, smooth muscle proliferation, inflammation and structural integrity of the vessel wall. We propose to investigate several potential genes involved in these processes. Primary Aims: 1. To determine the association between carotid IMT, distensibility and polymorphisms of 16 candidate genes in the three race/ethnic groups from Northern Manhattan. 2. To create marker haplotypes and perform haplotype analysis using in-house newly developed programs. 3. To explore a newly developed statistical method to evaluate the overall genetic effects from all candidate genes to obtain "whole-pathway" effects.

描述（由申请人提供）：颈动脉内膜-中膜厚度（IMT）和扩张率分别代表结构性和功能性颈动脉亚临床疾病。它们可以通过超声测量，并且可以用作临床中风/心血管事件的中间表型。研究表明颈动脉IMT升高或扩张性降低是心肌梗死和脑卒中的独立危险因素。此外，家族研究报道，这两种中间表型都有明显的遗传性，这表明遗传对颈动脉厚度和硬度的发展有很强的影响。这些发现保证了将遗传标记映射到这两种表型的努力。