MOLECULAR GENETICS OF ACE

ACE 的分子遗传学

• 批准号: 6188674
• 负责人: RIchard Stanley Cooper
• 金额: $ 4.03万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6188674
• 关键词: African Caribbean; cardiovascular disorder epidemiology; clinical research; enzyme activity; genetic polymorphism; genetic susceptibility; human data; human genetic material tag; human population genetics; hypertension; linkage disequilibriums; peptidyl dipeptidase A

Within the framework of an on-going collaborative study of hypertension in populations of African origin, the applicants propose to extend work on the renin-angiotensin system (RAS). A population-based prevalence survey has been completed in Jamaica and will provide samples for genetic analysis. Ten polymorphisms of the angiotensin-converting enzyme (ACE) will be typed in 1,000 individuals from the hypertension survey. Pointwise analyses of linkage disequilibrium between alleles at these polymorphic sites and phenotypes of interest (serum ACE activity, blood pressure as a continuous trait and hypertension as a dichotomous trait) will be conducted. To narrow the critical interval within the ACE gene which contains molecular variants that contribute to the variance of serum ACE activity and/or blood pressure in this population, additional measured haplotype" analyses will be carried out. Finally, sequencing will be undertaken in the critical interval of the ACE gene to define the existing genetic variation. Support is requested in this application for laboratory analyses at the Tropical Metabolism Research Unit (TMRU), Kingston, Jamaica. Dr. Colin McKenzie, who will carry out the genotyping, recently completed a DPhil at Oxford University in the Wellcome Trust Centre for Human Genetics. The proposed research is a direct extension of his work at Oxford. An important advantage provided by the Jamaican population is the presence of extensive variation in haplotypes. This diversity allows for the analysis of ancestral recombination events to refine the position of variants which influence ACE levels. Dr. McKenzie will be supported by continued collaboration with Oxford investigators, as well as the PI and statistical geneticists at Loyola. A strong collaborative relationship has been established over the last 5 years between the TMRU and Loyola University Medical School. Three NIH grants have been jointly funded between these groups, and a number of publications have been co-authored. This scientific interchange will be further enhanced by the opportunity for new original research at the TMRU. Substantial work on the genetics of hypertension, with a focus on the RAS, has already been already initiated within this collaborative research project, directed by Dr. Cooper and the group at Loyola. However, Dr. McKenzie's contribution will be unique, and will combine advanced genetic methods with the epidemiologic resources that exist within the parent project. In addition, this work will further aid in the development of research capacity within the Caribbean.

在非洲血统人群中进行的高血压研究的框架内，申请人建议扩展肾素 - 血管紧张素系统（RAS）的工作。 基于人群的患病率调查已在牙买加完成，并将提供遗传分析的样本。 血管紧张素转换酶（ACE）的十种多态性将在高血压调查中输入1,000名个体。 这些多态性位点和感兴趣的表型（血清ACE活性，血压作为连续特征和高血压作为二分法性状）的连锁不平衡的分析。 为了缩小ACE基因内的临界间隔，其中包含分子变异，这些变异有助于该人群中血清ACE活性和/或血压的方差，将进行其他测量的单倍型“将进行“进行分析”。最后，将在ACE基因的关键间隔中进行测序以定义现有的遗传分析。 （TMRU），金斯敦，麦肯齐（Colin McKenzie）博士，他将在惠康大学人类遗传学的牛津大学（Oxpord University of Mustical of Shautsive of Surgienty of Surgiention of Shaftiral of Shaprivity of Shaustival of Shaustive of Shaftiral of Shaprivity of Shaimention of Shaimention of Shaimentive of Shaimentive of Shaimestion of Shaimention of Haheast of Haheast，影响ACE水平的变体的位置将由牛津研究员以及Loyola的PI和统计遗传学家的持续合作提供支持。在过去的5年中，TMRU和Loyola大学医学院之间建立了牢固的合作关系。 这些群体之间已经共同资助了三项NIH赠款，并共同拥有了许多出版物。 TMRU的新原始研究机会将进一步增强这种科学交流。关于高血压遗传学的大量工作，重点关注RA，已经在由库珀博士和洛约拉小组指导的该协作研究项目中开始。但是，麦肯齐博士的贡献将是独一无二的，并将将先进的遗传方法与父母项目中存在的流行病学资源相结合。 此外，这项工作将进一步帮助加勒比海地区的研究能力发展。