Genetics of Chronic Kidney Disease

慢性肾脏疾病(CKD)困扰着美国11%的成年人口。对慢性肾脏病的易感性各不相同 相当大，这表明了遗传因素的作用。对慢性肾脏病遗传预测因子的了解可能导致 更好地识别和治疗高危个体，以防止发病率和流行率的上升 终末期肾病。 动脉病遗传流行病学网络(热那亚)进行了全基因组链接和 识别影响血压的基因与脑、心脏、动脉硬化的相关性研究 以及高血压的外周血管并发症。拟议的调查将扩大这些努力 通过确定CKD的遗传预测因素，以前很好地描述了欧洲-白人和非洲人- 美国有2个或2个以上的高血压成员。我们建议确定慢性肾脏病的遗传预测因子 在这些种族多样、高风险的人群中，实现以下具体目标： 目标1：确定动脉硬化的传统危险因素还是新的危险因素(已经通过 热那亚)预测1000名欧洲白人和1000名非洲裔美国人的肾小球滤过率或蛋白尿 兄弟姐妹。 目的2：确定&gt；250候选基因是否存在双等位基因多态性 动脉硬化性脑血管、心脏血管和外周血管并发症(已经通过 热那亚)预测1000名欧洲白人和1000名非洲裔美国人的肾小球滤过率或蛋白尿 兄弟姐妹。 目的3：确定387个高度多态的串联重复序列标记基因座中是否有任何一个跨越基因组 (已由热那亚测量)与影响肾小球滤过率或蛋白尿的基因有关 超过1000对欧洲白人和1000对非洲裔美国人兄弟姐妹。

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 1000African-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-Americansibling pairs.