Genetics of Kidney Disease in Zuni Indians

祖尼印第安人肾脏疾病的遗传学

• 批准号: 6875794
• 负责人: PHILIP George ZAGER
• 金额: --
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6875794
• 关键词: Native Americans; albumins; chronic renal failure; clinical research; cooperative study; creatinine; diabetes mellitus; diabetes mellitus genetics; diabetic nephropathy; epidemiology; family genetics; gene environment interaction; genetic markers; genetic polymorphism; genetic screening; genetic susceptibility; human population genetics; human subject; kidney disorder; linkage mapping; phenotype; siblings; urinalysis

DESCRIPTION (provided by applicant): The Zuni Pueblo, in NM, is home to a small, geographically isolated, tribe, which has been relatively endogamous for hundreds of years. The Zuni Pueblo is currently experiencing a major epidemic of renal disease. This epidemic, unlike those in other American Indian communities, is attributable to high rates of diabetic and non-diabetic renal disease. Mesangiopathic nephropathy, most commonly IgA nephropathy (IgAN), comprises the majority of non-diabetic renal disease. Almost everyone at Zuni has a relative with renal disease, leading to strong community support for collaborative research. This has created a unique opportunity to identify genetic and environmental factors that modulate the susceptibility to renal disease and intermediate phenotypes. To maximize this opportunity, we established the, NIDDK funded, Zuni Kidney Project (ZKP). We have conducted a population-based survey of Zuni residents 5 years of age. We have ascertained family structure, quantified glycemic control, proteinuria, and renal function, and isolated DNA in over 1,650 participants. The ZKP is participating in FIND, a NIDDK funded sib pair-based consortium charged with identifying diabetic nephropathy susceptibility genes. However, the study design and ascertainment criteria in FIND do not take advantage of the unique population structure of Zuni. This has limited the ZKP's involvement in FIND and led to under-utilization of this unique resource. The present application requests support to conduct a study of extended families to identify genomic segments that modulate susceptibility to diabetic and non-diabetic renal disease and intermediate phenotypes. We will identify risk factors that show the strongest evidence for single gene effects and map those genes to specific chromosomal regions. Our investigative team includes the Zuni Pueblo, University of New Mexico Health Sciences Center (UNMHSC), and Southwest Foundation for Biomedical Research, and Strong Heart Study.

描述（由申请人提供）：新墨西哥州的祖尼普韦布洛 (Zuni Pueblo) 是一个地理上孤立的小部落的家园，数百年来该部落一直保持相对的同族通婚。祖尼普韦布洛目前正在经历一场严重的肾病流行。与其他美洲印第安人社区不同，这种流行病是由于糖尿病和非糖尿病肾病的高发病率造成的。系膜病性肾病，最常见的是 IgA 肾病 (IgAN)，占非糖尿病肾病的大部分。 Zuni 的几乎每个人都有一位患有肾病的亲戚，这为合作研究带来了社区的大力支持。这为识别调节肾脏疾病和中间表型易感性的遗传和环境因素创造了独特的机会。为了最大限度地利用这一机会，我们建立了 NIDDK 资助的 Zuni 肾脏项目 (ZKP)。我们对祖尼 5 岁居民进行了人口调查。我们确定了 1,650 多名参与者的家庭结构，量化了血糖控制、蛋白尿和肾功能，并分离了 DNA。 ZKP 正在参与 FIND，这是一个由 NIDDK 资助的同胞对联盟，负责识别糖尿病肾病易感基因。然而，FIND 的研究设计和确定标准并没有利用祖尼独特的人口结构。这限制了 ZKP 对 FIND 的参与，并导致这一独特资源的利用不足。 本申请请求支持对大家庭进行研究，以确定调节糖尿病和非糖尿病肾病易感性的基因组片段以及中间表型。我们将确定显示单基因效应最有力证据的风险因素，并将这些基因映射到特定的染色体区域。我们的调查团队包括 Zuni Pueblo、新墨西哥大学健康科学中心 (UNMHSC) 以及西南生物医学研究基金会和强心研究基金会。