Genes of Hypertension in African Americans

非裔美国人的高血压基因

• 批准号: 6784624
• 负责人: Theodore Kotchen
• 金额: $ 78.97万
• 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/6784624
• 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专注于确定动脉压的生理途径来识别导致非洲裔美国人高血压的基因。 在过去的六年中，我们为非洲裔美国人提供了与心血管和肾功能相关的表型的广泛特征。 基于最近完成的基因组扫描，我们已经确定了几个可能包含影响高血压相关表型基因的染色体区域，非裔美国人SIB对。 对于几种表型，在遗传分离的法国加拿大人群和/或在Dahl-Salt敏感X敏感X正常的棕色挪威大鼠的F2交叉中，在相关研究中也发现了重叠的QTL。 现在，我们建议使用SNP基因组扫描方法进行广泛的表型500高血压和500名非裔美国人受试者进行遗传关联研究。 为了使血压与高血压受试者进行明显的分离，将从基于人群的血压分布的下三分之一中选择正常的受试者。 高血压（BMI）和年龄。 包括表型基于它们与高血压的病理生理学和先前的“遗传力”证据的相关性。 用于SNP分析的候选基因将在两个QTL的染色体区域中选择，我们以前证明我们与高血压相关的表型有关，这是1染色体上的体重指数的QTL，在第18个染色体上进行微量白蛋白尿的QTL QTL。它们与高血压的相关性，包括与大鼠或小鼠有关血压相关的QTL的序列保守性。 该项目的最终目标是确定是否可以鉴定出不同的血压相关表型簇，以允许高血压个体分层为不同的亚组，以促进分析高血压的遗传决定因素和/或为有助于这些性状的基因提供机械性。