NHLBI MINORITY SCHOOL FACULTY DEVELOPMENT AWARD

描述 (摘自申请者的摘要)拟议研究的长期目标 是为了深入了解原发性高血压的遗传基础。 高血压及其影响是美国的一个主要健康问题 尤其是在非裔美国人社区中，情况尤其严重。 由于高血压的发病率高得不成比例 非洲裔美国人，这个项目将分析非洲人后裔 独家。通过选择这个高度受苦的种族群体问题 遗传异质性将被最小化，潜在的遗传因素 应该更容易解剖。受影响的兄弟姐妹和家庭最初将 将从田纳西州纳什维尔和西非加纳农村和城市征聘。这个 这些人群的高血压发病率差异很大，美国 黑人比例最高，其次是城市和农村加纳人。 对这些群体的比较将在评估遗传 与环境对高血压的贡献。 本研究中使用的方法是确定其中一个兄弟姐妹对 或者两者都有高血压，并确定特定等位基因的贡献 使用等位基因共享方法。最初有三个 候选基因，血管紧张素转换酶、血管紧张素原和肾素， 并对紧密相连的标记进行分析。所有这些基因座都在 同样的生理途径，并被假设在 控制血压。聚合酶链式反应获得的DNA片段分析 扩增将被用来检测特定的等位基因状态 不同的个体。之后，将进行系统的基因组搜索 以确定导致高血压的其他基因组区域 压力表型。此设计将检测与以下各项的任何关联 基因和高血压。随着新数据的出现，其他候选基因 也将在这些科目中进行分析。

DESCRIPTION (Adapted from applicant's abstract) The long term goal of the proposed study is to gain insight into the genetic basis of essential hypertension. Hyper-tension and its effects are a major health problem in the United States, and are particularly severe within the African-American community. Because of the disproportionately high incidence of hypertension in African-Americans, this project will analyze people of African descent exclusively. By choosing this highly afflicted ethnic group problems of genetic heterogeneity will be minimized and the underlying genetic factors should be easier to dissect. Affected sib-pairs and families will initially be recruited from Nashville, TN and rural and urban Ghana, West Africa. The incidence of hypertension in these populations varies dramatically, with US Blacks being highest, followed by urban and the rural Ghanaians. Comparisons of these populations will be important in assessing the genetic vs. environmental contribution to hyper-tension. The approach to be used in this study is to ascertain sib-pairs in which one or both have hypertension and determine the contribution of specific alleles to hypertension, using an allele sharing methodology. Initially three candidate loci, angiotensin I converting enzyme, angiotensinogen, and renin, and closely linked markers will be analyzed. All of these loci are in the same physiological pathway and have been hypothesized to be important in the control of blood pressure. Analysis of DNA segments obtained by PCR ampli-fication will be used to detect specific allele states in the different individuals. Following this a systematic genome search will be done to identify other genomic regions that contribute to the high blood pressure phenotype. This design will detect any associations with these genes and hypertension. As new data become available, other candidate genes will also be analyzed in these subjects.