Y Chromosome Genes and Essential Hypertension in American Males

首席调查员的职业发展计划和目标 伊克希德·伊姆莫林博士在德克萨斯农工大学接受动物遗传学培训，并开始研究人类遗传学 作为大学内分泌学、糖尿病和营养学部的博士后研究员 巴尔的摩马里兰医学院(Pis：Alan Shuldiner和Braxton Mitchell)。这项拨款建议 将使他能够在遗传学高级研究人员的指导下发展他的研究技能 心血管疾病。他的主要目标是利用这个RIMI子奖来增加他的研究 通过逐步提高他对基因的兴趣的速度和生产力来提高竞争力 高血压(EH)的流行病学。该奖项将使Imumorin博士能够(I)产生和 在发展良好的高血压大鼠模型中验证初步数据；(Ii)在具有良好特征的 人类群体和(Iii)对选定的Y进行遗传关联分析 染色体基因与人类高血压。预计他将过渡到非RIMI来源 在5年期结束时提供外部支持。因为人们对男性专一性的作用知之甚少 Y(MSY)基因在EH中，这项建议打算启动一项长期研究计划，以了解 MSY基因如何影响EH以及MSY基因如何与其他常染色体基因相互作用导致EH 与绝经前女性相比，男性EH的明显性二型性患病率。在……里面 在随后的研究中，他希望(I)进行MSY基因的大规模表达分析，(Ii)获得//？- MSY在体内和体外各种男性器官和组织中表达的蛋白质数据：(Iii)进行大规模 MSY基因变异的规模鉴定和验证，(Iv)研究MSY和MY的基因-基因互作 常染色体基因座在涉及交感神经系统、脂类代谢、 钠的摄入和排泄、社会压力和与睾酮的相互作用以及(V)检查MSY 血液中涉及的环境应激源和药物等基因-环境相互作用 在病例对照和基于家庭的人类关联分析框架内的压力调节。 研究项目和增进对少数民族健康差距的了解 根据美国国立卫生研究院的说法，人们普遍认为，有许多疾病和障碍 对美国种族和少数民族人口的健康造成不成比例的影响。这是显而易见的 非洲裔美国人，西班牙裔美国人，美国印第安人，阿拉斯加原住民，一些亚裔美国人， 和其他太平洋岛民相比，他们面临着更高的风险和更差的健康状况 人口。在困扰少数民族的疾病中，原发性高血压是不成比例的。美国国立卫生研究院 的使命是更好地了解这种健康差距的遗传和环境基础 并减少卫生保健和健康结果不平等造成的人力和经济成本。 这个项目是为了利用由NHLBI资助的一项大型多种族研究-The 动脉粥样硬化的多种族研究(MESA)项目，以了解动脉粥样硬化以及种族和 种族差异可能会导致死亡率和发病率。我们的项目将能够进入一口井 美国四个主要种族/民族背景的特征研究人群，并将增加我们的 了解Y染色体上的基因是如何与大鼠(Sry)明显相关的 可能与种族/民族相互作用，推动这种健康差距。私家侦探已经组建了一支高度 具有超过60年心血管疾病遗传学经验的合格研究人员 人和大鼠高血压模型都进行了这项研究。

Career Developmental Plans and Objectives of Principal Investigator Dr. Ikhide Imumorin trained in animal genetics at Texas A&M University and got a start in human genetics as a Postdoctoral Research Fellow in the Division of Endocrinology, Diabetes and Nutrition at the University of Maryland School of Medicine, Baltimore (Pis: Alan Shuldiner and Braxton Mitchell). This grant proposal will enable him to develop his research skills under the mentorship of senior investigators in the genetics of cardiovascular disease. His primary goal is to utilize this RIMI sub-award to increase his research competitiveness by progressively enhancing the pace and productivity of his interests in the genetic epidemiology of essential hypertension (EH). This award will enable Dr. Imumorin to (i) generate and validate preliminary data in a well-developed hypertensive rat model; (ii) test the results in a wellcharacterized human population and (iii) conduct genetic association analysis of selected Y chromosome genes and human hypertension. It is expected that he will transition to non-RIMI sources of external support at the end of the 5-year period. Since very little is known about the role of male-specific Y (MSY) genes in EH, this proposal intends to launch a long-term research program to understand how MSY genes influence EH and how MSY genes interact with other autosomal genes to cause the apparent sexually dimorphic prevalence of EH in males compared to pre-menopausal females. In subsequent studies, he hopes to (i) conduct large scale expression analyses of MSY genes, (ii) obtain //?- vivo and in-vitro data on MSY expressed proteins in various male organs and tissues, (iii) undertake large scale identification and validation of MSY gene variants, (iv) examine gene-gene interactions of MSY and autosomal loci in multiple pathways involving genes of the sympathetic nervous system, lipid metabolism, sodium intake and excretion, social stress and interaction with testosterone action and (v) examine MSY gene-environment interactions such as environmental stressors and pharmacologies implicated in blood pressure regulation within the framework of case-control and family based association analyses in humans. Research Project and Advancing Understanding of Health Disparities in Minorities According to the NIH, it is widely recognized that there are many diseases and disorders that disproportionately affect the health of racial and ethnic minority populations in the United States. It is evident that African-Americans, Hispanic Americans, American Indians, Alaska Natives, some Asian-Americans, and other Pacific Islanders experience much higher risks and poorer health status than the general population. Among the diseases that disproportionately afflict minorities is essential hypertension. The NIH has a mission to better understand the genetic and environmental underpinnings of this disparity in health and to reduce the human and economic costs resulting from inequities in health care and health outcomes. This project has been proposed to take advantage of a large multi-ethnic study funded by the NHLBI - the Multi Ethnic Study of Atherosclerosis (MESA) project to understand atherosclerosis and how racial and ethnic differences may contribute to mortality and morbidity. Our project will be able to access a well characterized study population of four major racial/ethnic backgrounds in the U.S. and will increase our understanding of how genes on the Y chromosome one of which has been clearly implicated in rat (Sry) may interact with race/ethnicity to drive this health disparity. The PI has assembled a team of highly qualified investigators with a combined experience of over 60 years in genetics of cardiovascular disease in both human and the rat model of hypertension to undertake this study.