GENES AND SEVERE HYPERTENSION AMONG AFRICAN AMERICANS

非裔美国人的基因和严重高血压

• 批准号: 7378831
• 负责人: JEFFERY HUNTER YOUNG
• 金额: $ 0.11万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378831
• 关键词: GENES; SEVERE; HYPERTENSION; AMONG; AFRICAN

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. African-Americans bear the highest rates of hypertension in the world. The consequences of this burden are well known and include very high rates for stoke, heart disease, and renal disease. While we have made impressive gains in the understanding and treatment of hypertension, we have much more to do, especially among African-Americans. Thanks to the efforts of investigators at Johns Hopkins and many others, we now know many of the important exposures, but the allelic variants responsible for the predisposition to hypertension and its end-organ effects remain elusive. Therefore, we have designed, and begun to carry out, a family-based case-control study into the mechanism of hypertension emphasizing the genetic predisposition but including the environmental and cultural contexts. We hypothesize that common allelic variants of the genes encoding the G protein beta3 subunit, the alpha-subunit of the adducin cytoskeletal protein, the beta2- adrenergic receptor, the alpha and beta-subunits of the epithelial sodium channel, angiotensin-converting enzyme, and angiotensinogen are associated and linked with blood pressure level among African- Americans. We are recruiting 200 African-American probands with severe hypertension admitted to the Johns Hopkins Hospital, 200 unrelated normotensive African-American controls and the siblings of cases. The inclusion of participants from both ends of the blood pressure spectrum will maximize our ability to detect genes with small effects. Restricting recruitment to African-Americans from one environmental and cultural milieu will further maximize our power by limiting phenotypic, environmental and cultural heterogeneity. To control for the heterogeneity that remains, we will further characterize each participant's phenotype, exposure history, and family origins. We will limit confounding due to population substructure and admixture by obtaining a detailed genealogy and using sibling controls. Within the context of this family-based case-control study, we will test both association and linkage using the case-control analysis with family controls as well the sibling transmission/disequilibrium test. This epidemiological approach has the best chance of uncovering the genomic causes of hypertension given the mechanistic complexity of blood pressure regulation and the complexity of the population structure of African-Americans.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。非裔美国人的高血压率最高。这种负担的后果是众所周知的，包括斯托克，心脏病和肾脏疾病的率很高。尽管我们在理解和治疗高血压方面取得了令人印象深刻的收益，但我们还有很多事情要做，尤其是在非裔美国人中。多亏了约翰·霍普金斯（Johns Hopkins）和其他许多人的调查人员的努力，我们现在知道许多重要的暴露，但是负责高血压易感性及其最终器官效应的等位基因变体仍然难以捉摸。因此，我们已经设计并开始进行基于家庭的病例对照研究，以强调遗传易感性但包括环境和文化背景的高血压机制。 We hypothesize that common allelic variants of the genes encoding the G protein beta3 subunit, the alpha-subunit of the adducin cytoskeletal protein, the beta2- adrenergic receptor, the alpha and beta-subunits of the epithelial sodium channel, angiotensin-converting enzyme, and angiotensinogen are associated and linked with blood pressure level among非裔美国人。 我们正在招募200名非裔美国人证据，并招募了约翰·霍普金斯医院（Johns Hopkins Hospital）的严重高血压，200名不相关的非裔美国人控制和案件兄弟姐妹。包括血压谱系两端的参与者将最大程度地提高我们检测具有较小作用基因的能力。从一个环境和文化环境中限制向非裔美国人招募将通过限制表型，环境和文化异质性进一步最大化我们的力量。为了控制剩下的异质性，我们将进一步描述每个参与者的表型，暴露历史和家庭起源。我们将通过获得详细的家谱并使用同级控制来限制由于人口子结构和混合而引起的混杂。在这项基于家庭的病例对照研究的背景下，我们将使用与家庭对照的病例对照分析以及同级传播/不平衡测试测试关联和链接。鉴于血压调节的机理复杂性和非裔美国人种群结构的复杂性，这种流行病学方法具有揭示高血压基因组原因的最佳机会。