Genetics of Kidney Disease in Zuni Indians

描述（由申请人提供）：祖尼普韦布洛，在新墨西哥州，是一个小的，地理上孤立的，部落，这已经相对通婚了几百年。祖尼普韦布洛目前正在经历一场重大的肾病流行病。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。系膜性肾病，最常见的是伊加肾病（IgAN），包括大多数非糖尿病肾病。 祖尼的几乎每个人都有肾病亲属，这使得社区对合作研究的支持非常强大。这创造了一个独特的机会，以确定遗传和环境因素，调节肾脏疾病的易感性和中间表型。为了最大限度地利用这一机会，我们建立了NIDDK资助的祖尼肾脏项目（ZKP）。我们对5岁以上的祖尼居民进行了一项基于人口的调查。我们已经确定了家庭结构，量化血糖控制，蛋白尿和肾功能，并在超过1,650名参与者中分离DNA。ZKP正在参与FIND，这是一个由NIDDK资助的基于同胞对的联盟，负责识别糖尿病肾病易感基因。然而，FIND中的研究设计和确定标准并未利用祖尼的独特人群结构。这限制了津巴布韦警察局参与寻找失踪人员方案，并导致这一独特资源利用不足。 本申请请求支持进行大家族的研究以鉴定调节对糖尿病和非糖尿病肾病的易感性的基因组区段和中间表型。我们将确定风险因素，显示单基因效应的最强有力的证据，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祖尼普韦布洛、新墨西哥州大学健康科学中心（UNMHSC）、西南生物医学研究基金会和强心研究。

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.