Genes of Hypertension in African Americans

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鉴定导致非洲裔美国人高血压的基因。 在过去的6年中，我们广泛的特点，非洲裔美国人的表型相关的心血管和肾功能。 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含有影响高血压相关表型的基因，在高血压，非洲裔美国人同胞对。 对于几种表型，重叠的QTL也已确定在相关的研究中，在遗传隔离的法裔加拿大人口和/或在同源染色体区域中的F2杂交达尔盐敏感x血压正常的布朗挪威大鼠。 我们现在建议广泛表型500高血压和500血压正常的非裔美国人进行遗传关联研究，使用SNP基因组扫描方法。 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下三分之一中选择血压正常的受试者。 高血压（BMI）和年龄。 表型的纳入是基于其与高血压病理生理学的相关性和先前的“遗传性”证据。“SNP分析的候选基因将在两个QTL的染色体区域内选择，我们以前已经证明这两个QTL与高血压相关的表型有关-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。 SNP分析将在这些QTL中的每个QTL内的15%的基因中进行，并且基因将基于其与高血压的相关性进行选择，包括记录的大鼠或小鼠血压相关QTL的序列保守性。 该项目的最终目标是确定是否可以识别出不同的血压相关表型簇，这将允许将高血压个体分层为不同的亚组，以便于分析高血压的遗传决定因素和/或提供有助于这些性状的基因的机制线索。

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.