Genes of Hypertension in African Americans

非裔美国人的高血压基因

• 批准号: 6940861
• 负责人: Theodore Kotchen
• 金额: $ 82.61万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6940861
• 关键词: African American; cardiovascular disorder epidemiology; clinical research; familial hypertension; family genetics; genetic susceptibility; human genetic material tag; human subject; linkage mapping; phenotype; quantitative trait loci; single nucleotide polymorphism

DESCRIPTION (provided by applicant): We hypothesize that we will be able to identify genes contributing to hypertension in African Americans by focusing on the physiological pathways that determine arterial pressure. Over the past 6 years, we have extensively characterized African Americans for phenotypes related to cardiovascular and renal function. Based on recently completed genome scans, we have identified several chromosomal regions likely to contain genes influencing hypertension-related phenotypes in hypertensive, African American sib pairs. For several phenotypes, overlapping QTLs have also been identified in related studies in a genetically isolated French Canadian population and/or in homologous chromosomal regions in the F2 cross of Dahl-salt sensitive x normotensive Brown Norway rats. We now propose to extensively phenotype 500 hypertensive and 500 normotensive African American subjects to conduct a genetic association study, using a SNP genomic scan approach. To achieve a clear separation of blood pressures from hypertensive subjects, normotensive subjects will be selected from the lower third of the population-based blood pressure distribution. Hypertensive (BMI), and age. Inclusion of phenotypes is based on their relevance to the pathophysiology of hypertension and prior evidence of "heritability." Candidate genes for SNP analysis will be selected within chromosomal regions of two QTLs that we have previously demonstrated to be linked to hypertension-related phenotypes--a QTL for body mass index on chromosome 1 and a QTL for microalbuminuria on chromosome 18. SNP analyses will be carried out in 15 percent of the genes within each of these QTLs, and genes will be selected on the basis of their relevance to hypertension, including documented sequence conservation for blood pressure related QTLs with rat or mouse. The final goal of the project is to determine if distinct clusters of blood pressure related phenotypes can be identified that will permit stratification of hypertensive individuals into distinct subgroups to facilitate the analysis of the genetic determinants of hypertension and/or provide mechanistic leads to genes contributing to these traits.

描述（由申请人提供）：我们假设我们将能够通过关注决定动脉压的生理途径来识别导致非裔美国人高血压的基因。在过去的6年里，我们广泛地研究了非裔美国人与心血管和肾脏功能相关的表型。基于最近完成的基因组扫描，我们已经确定了几个染色体区域可能包含影响高血压相关表型的基因，在高血压，非洲裔美国同胞对。在一些表型的相关研究中，在遗传分离的法裔加拿大人群和/或dahl -盐敏感x正常褐挪威大鼠的F2杂交的同源染色体区域中也发现了重叠的qtl。我们现在建议对500名高血压和500名正常的非裔美国人进行广泛的表型分析，使用SNP基因组扫描方法进行遗传关联研究。为了实现血压与高血压受试者的明确分离，将从基于人群的血压分布的低三分之一中选择血压正常的受试者。高血压（BMI）和年龄。包括表型是基于它们与高血压病理生理的相关性和先前的“遗传性”证据。SNP分析的候选基因将在我们之前已经证明与高血压相关表型相关的两个QTL的染色体区域内选择——1号染色体上的体重指数QTL和18号染色体上的微量白蛋白尿QTL。研究人员将对每个qtl中15%的基因进行SNP分析，并根据基因与高血压的相关性进行选择，包括记录在案的大鼠或小鼠血压相关qtl的序列保护。该项目的最终目标是确定是否可以识别出与血压相关的表型的不同集群，从而将高血压个体分层为不同的亚组，以促进对高血压遗传决定因素的分析和/或提供导致这些特征的基因的机制。