Genetics of Kidney Disease in Zuni Indians

描述(申请人提供)：新墨西哥州的Zuni Pueblo是一个地理上与世隔绝的小部落的家园，该部落数百年来一直实行内婚制。祖尼普韦布洛目前正在经历一场重大的肾脏疾病流行。与其他美洲印第安人社区不同的是，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。系膜病理性肾病，最常见的是IgA肾病(IgAN)，占非糖尿病肾病的大多数。 在Zuni，几乎每个人都有肾脏疾病的亲戚，这导致社区对合作研究的大力支持。这创造了一个独特的机会来确定调节肾脏疾病和中间表型易感性的遗传和环境因素。为了最大限度地利用这个机会，我们建立了由NIDDK资助的祖尼肾脏项目(ZKP)。我们对5岁的祖尼居民进行了以人口为基础的调查。我们已经确定了家庭结构，量化了血糖控制，蛋白尿和肾功能，并分离了超过1,650名参与者的DNA。ZKP正在参与Find，这是一个由NIDDK资助的以同胞对为基础的联盟，负责识别糖尿病肾病的易感基因。然而，FIND中的研究设计和确定标准并没有利用祖尼独特的种群结构。这限制了ZKP参与搜寻工作，并导致这一独特资源得不到充分利用。 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脏疾病易感性的基因组片段和中间表型。我们将确定单基因效应的最有力证据的危险因素，并将这些基因定位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、西南生物医学研究基金会和强心脏研究。

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.