Genetics of Kidney Disease in Zuni Indians

新墨西哥州的祖尼普韦布洛是一个地理上与世隔绝的小部落的家园，这个部落相对 数百年来的内婚制。Zuni Pueblo目前正在经历一场重大的肾脏病流行 疾病。与其他美洲印第安人社区不同，这种流行病可归因于高发病率 糖尿病和非糖尿病肾病。系膜病理性肾病，最常见的是IgA肾病 (IGAN)，构成了非糖尿病肾病的大多数。 Zuni的几乎每个人都有一个患有肾脏疾病的亲戚，这导致了社区对 合作研究。这创造了一个独特的机会来识别遗传和环境因素 调节对肾脏疾病和中间表型的易感性。为了最大限度地实现这一点 机会，我们建立了由NIDDK资助的祖尼肾脏项目(ZKP)。我们已经进行了一次 以人口为基础的祖尼居民调查--5岁。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1,650多名参与者中提取DNA。这个 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 肾病易感基因。然而，FIND中的研究设计和确定标准没有采取 祖尼独特的人口结构优势。这限制了ZKP对Find和Lead的参与 对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基因组 调节糖尿病和非糖尿病肾脏疾病易感性的节段和中间体 表型。我们将找出单基因效应的最有力证据的风险因素，并绘制地图。 这些基因被转移到特定的染色体区域。我们的调查小组包括祖尼·普韦布洛大学 新墨西哥健康科学中心和西南生物医学研究基金会，以及 强心研究。

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.