NHLBI MINORITY SCHOOL FACULTY DEVELOPMENT AWARD

描述 （改编自申请人摘要）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。 在美国，高血压及其影响是一个主要的健康问题。 在非洲裔美国人社区中尤为严重。 由于高血压的发病率不成比例的高， 非洲裔美国人，这个项目将分析非洲裔人 独家。 通过选择这个高度困扰的民族群体的问题， 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将首先 从田纳西州的纳什维尔和西非加纳的农村和城市招募。 的 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。 这些人群的比较将是重要的遗传评估 vs.环境因素对高血压的影响 在这项研究中使用的方法是确定同胞对，其中一个 或者两者都患有高血压， 与高血压的关系。 最初三 候选基因座，血管紧张素I转化酶，血管紧张素原，和肾素， 并分析紧密连锁的标记。 所有这些位点都在 相同的生理途径，并已被假设是重要的， 控制血压。 通过PCR获得的DNA片段的分析 扩增将用于检测特定等位基因状态， 不同的个体 在此之后，将进行系统的基因组搜索， 这样做是为了确定其他基因组区域，有助于高血 压力表型 此设计将检测与这些 基因与高血压 随着新数据的出现，其他候选基因 也将在这些主题中进行分析。

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.