Genetics of Chronic Kidney Disease

描述(由申请人提供)：慢性肾脏疾病(CKD)困扰着11%的美国成年人口。对CKD的易感性差异很大，这表明遗传因素起到了一定作用。了解慢性肾脏病的遗传预测因素可能会导致更好的方法来识别和治疗高危个体，以防止终末期肾脏疾病发病率和流行率的上升。动脉病遗传流行病学网络(Genoa)进行了全基因组链接和关联研究，以确定影响血压和高血压的动脉硬化性脑血管、心脏和外周血管并发症的基因。这项拟议的研究将通过确定先前特征良好的有2名或2名以上高血压成员的欧洲白人和非裔美国人兄弟姐妹中CKD的基因预测因素来扩展这些努力。我们建议通过实现以下特定目标，在这些不同种族的高危人群中确定CKD的遗传预测因素：目标1：确定传统的或新的动脉硬化危险因素(已由热那亚测量)是否预测1000名欧洲白人和1000名非洲裔美国兄弟姐妹的肾小球滤过率或蛋白尿。目的2：确定在1000名欧洲白人和1000名非洲裔美国同胞中，高血压或其动脉硬化性脑血管、心脏和外周血管并发症的候选基因&gt；250的双等位基因多态性是否可以预测肾小球滤过率或蛋白尿。目的3：在1000对欧洲白人和1000对非洲裔美国同胞中，确定跨越基因组的387个高度多态的串联重复序列标记基因座(已由Genoa测量)中是否有任何一个与影响肾小球滤过率或蛋白尿的基因连锁。

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) afflicts 11% of the adult US population. Susceptibility to CKD varies considerably, suggesting a role for genetic factors. Knowledge of genetic predictors of CKD may lead to better methods of identifying and treating individuals at risk to prevent the rising incidence and prevalence of endstage renal disease. The Genetic Epidemiology Network of Arteriopathy (GENOA) has conducted genomewide linkage and association studies to identify genes influencing blood pressure and the arteriosclerotic cerebral, cardiac, and peripheral vascular complications of hypertension. The proposed investigation will extend those efforts by identifying genetic predictors of CKD in previously well-characterized European-white and African- American sibships with 2 or more hypertensive members. We propose to identify genetic predictors of CKD in these ethnically diverse, high-risk cohorts by accomplishing the following specific aims: Aim 1: Determine whether conventional or novel risk factors for arteriosclerosis (already measured by GENOA) predict glomerular filtration rate or albuminuria in 1000 European-white and 1000 African-American siblings. Aim 2: Determine whether diallelic polymorphisms in >250 candidate genes for hypertension or its arteriosclerotic cerebral, cardiac, and peripheral vascular vascular complications (already measured by GENOA) predict glomerular filtration rate or albuminuria in 1000 European-white and 1000 African-American siblings. Aim 3: Determine whether any of 387 highly polymorphic tandem repeat marker loci spanning the genome (already measured by GENOA) are linked to genes influencing glomerular filtration rate or albuminuria in more than 1000 European-white and 1000 African-American sibling pairs.