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孤立的小部落的家园， 数百年来一直是近亲通婚祖尼普韦布洛目前正在经历一场严重的肾衰竭流行病， 疾病与其他美洲印第安人社区不同，这种流行病是由于高发病率， 糖尿病和非糖尿病肾病。系膜性肾病，最常见的伊加肾病 （IgAN），包括大多数非糖尿病肾病。 祖尼的几乎每个人都有一个患有肾病的亲戚，这导致了社区对肾脏疾病的强烈支持。 合作研究。这就创造了一个独特的机会来确定遗传和环境因素 调节肾脏疾病和中间表型的易感性。为了最大化这一点 我们利用这个机会，建立了由NIDDK资助的祖尼肾脏项目（ZKP）。我们已进行 对祖尼族5岁以下居民进行的人口调查。我们已经确定了家庭结构， 定量血糖控制，蛋白尿和肾功能，并在超过1,650名参与者中分离DNA。的 ZKP正在参与FIND，这是一个由NIDDK资助的、基于同胞对的联盟，负责识别糖尿病患者。 肾病易感基因然而，FIND中的研究设计和确定标准并不采用 祖尼独特的人口结构的优势。这限制了ZKP对FIND的参与， 这一独特资源的利用不足。 本申请请求支持进行大家族的研究以鉴定基因组DNA。 调节糖尿病和非糖尿病肾病易感性的节段和中间 表型我们将确定风险因素，显示单基因效应的最有力证据，并绘制 将这些基因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， 新墨西哥州健康科学中心（UNMHSC）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.