Genetics /Diabetic Nephropathy /Mexican-Americans /Afric

遗传学/糖尿病肾病/墨西哥裔美国人/非洲

• 批准号: 7036303
• 负责人: Susanne B Nicholas
• 金额: $ 17.5万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 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 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7036303
• 关键词: African American; Hispanic Americans; clinical research; cooperative study; diabetes mellitus genetics; diabetic nephropathy; diabetic retinopathy; family genetics; genetic polymorphism; genetic susceptibility; genome; genotype; health disparity; human genetic material tag; human subject; linkage mapping; medical outreach /case finding; noninsulin dependent diabetes mellitus; pathologic process; patient oriented research; phenotype; racial /ethnic difference

DESCRIPTION (provided by applicant): Diabetic Nephropathy is the leading cause of end stage renal failure in the United States. Statistics indicate that certain ethnic groups, such as Mexican Americans, Pima Indians and African Americans are disproportionately affected by diabetes and its complications including diabetic nephropathy and diabetic retinopathy. Studies done in Pima Indians have demonstrated strong evidence for the presence of genetic factors that may determine susceptibility to develop these complications. The Family Investigation of Nephropathy and Diabetes (FIND), which began in 1999, was designed to identify some of the genetic determinants of both Diabetic Nephropathy and Diabetic Retinopathy in several ethnic groups. The UCLA Participating Investigator Center (PIC) has been responsible primarily for recruitment of Mexican Americans into the study. The UCLA PIC has consistently been a major contributor to the overall recruitment population of the FIND study. As of January 2005, Dr. Susanne B. Nicholas, upon the request of the NIH/NIDDK and approval of the Executive Chair of the UCLA Department of Medicine has assumed the position of Principal Investigator of the UCLA FIND Study. One of the specific aims of the proposal is to complete the goals of the original FIND project. This will entail activities such as data cleaning, completion of phenotyping for families that are currently enrolled in the Retinopathy Study but are missing medical record information or laboratory data that will resolve their eligibility for the study. It will also involve recall of subjects and redraw of blood samples for DNA extraction. We also propose to use stored frozen blood for whole genome amplification of DNA by Phi29 rolling circle DNA replication. This in vitro process will facilitate the production of high-fidelity DNA that can be used for genotyping in the event of participant mortality or loss of follow-up. This will maintain the integrity of the central database. Since recruitment of African Americans into the study has been overall low, we propose to recruit African Americans for the Mapping Admixture Linkage Disequilibrium (MALD) study. Working in conjunction with the other PICs, a Candidate gene grant application based on the candidate genes obtained so far will be submitted. The final year of the project will focus more heavily on manuscript preparation. Dr. Nicholas will be directly involved in all aspects of the project.

描述(由申请人提供)： 糖尿病肾病是美国终末期肾功能衰竭的主要原因。统计数据表明，某些族裔群体，如墨西哥裔美国人、皮马印第安人和非裔美国人，受糖尿病及其并发症(包括糖尿病肾病和糖尿病视网膜病变)的影响不成比例。在皮马印第安人身上进行的研究已经证明，存在可能决定发生这些并发症的易感性的遗传因素。1999年开始的糖尿病肾病和糖尿病家族调查(FIND)旨在确定几个民族中糖尿病肾病和糖尿病视网膜病变的一些基因决定因素。加州大学洛杉矶分校参与调查中心(PIC)主要负责招募墨西哥裔美国人参加这项研究。加州大学洛杉矶分校的PIC一直是FIND研究总体招聘人数的主要贡献者。截至2005年1月，应NIH/NIDDK的要求和加州大学洛杉矶分校医学部执行主席的批准，苏珊娜·B·尼古拉斯博士已担任加州大学洛杉矶分校FIND研究的首席研究员。 该提案的具体目标之一是完成最初的Find项目的目标。这将需要一些活动，如数据清理，为目前已登记参加视网膜病研究但缺少病历信息或实验室数据的家庭完成表型分析，以确定其是否符合研究条件。它还将涉及召回受试者和重新抽取血液样本以提取DNA。我们还建议使用保存的冰冻血液通过Phi29滚环DNA复制进行DNA全基因组扩增。这一体外过程将促进高保真DNA的生产，在参与者死亡或失去随访的情况下，可用于基因分型。这将保持中央数据库的完整性。由于非洲裔美国人加入这项研究的总体水平较低，我们建议招募非裔美国人参与地图混合链接不平衡(MALD)研究。与其他PIC合作，将提交基于到目前为止获得的候选基因的候选基因资助申请。该项目的最后一年将更加注重手稿的准备。尼古拉斯博士将直接参与该项目的各个方面。