Genetics of Chronic Kidney Disease

慢性肾脏病的遗传学

• 批准号: 7354102
• 负责人: STEPHEN T TURNER
• 金额: $ 47.3万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-20 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7354102
• 关键词: Adult; African; African American; Age; Albumins; Albuminuria; American; Animal Model; Arterial Disorder; Arteriosclerosis; Blood Pressure; Blood Vessels; Body Size; Body Surface Area; C-reactive protein; Candidate Disease Gene; Cardiac; Cerebrum; Cessation of life; Chronic Kidney Failure; Creatinine; Diabetes Mellitus; Dialysis procedure; Disease Marker; Dyslipidemias; European; Fibrinogen; Genes; Genetic; Genetic Polymorphism; Genome; Glomerular Filtration Rate; Gold; Homocysteine; Homocystine; Human; Hypertension; Incidence; Individual; Investigation; Iothalamate; Kidney Diseases; Kidney Transplantation; Knowledge; LDL Cholesterol Lipoproteins; Lead; Link; Lipoprotein (a); Lipoprotein (a-); Measures; Methods; Mexican Americans; Myocardial Infarction; Peripheral; Physical Dialysis; Population; Predisposition; Prevalence; Research Personnel; Risk; Risk Factors; Role; Serum; Serum Markers; Severities; Siblings; Smoking; Standards of Weights and Measures; Stroke; Tandem Repeat Sequences; Urine; Woman; cohort; cost; genetic epidemiology; member; men; nephrogenesis; novel; post gamma-globulins; prevent; programs; sex

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.

11% 的美国成年人患有慢性肾病 (CKD)。对 CKD 的易感性各不相同 相当大，表明遗传因素的作用。了解 CKD 的遗传预测因素可能会导致 识别和治疗高危人群的更好方法，以防止发病率和流行率上升 终末期肾病。 动脉病遗传流行病学网络 (GENOA) 进行了全基因组连锁和 关联研究以确定影响血压和脑动脉、心脏、 以及高血压周围血管并发症。拟议的调查将扩大这些努力 通过在先前明确描述的欧洲白人和非洲人中识别 CKD 的遗传预测因子 美国同胞中有 2 名或以上患有高血压的成员。我们建议确定 CKD 的遗传预测因素 通过实现以下具体目标，在这些种族多样化的高风险人群中： 目标 1：确定动脉硬化的传统危险因素还是新的危险因素（已通过测量 GENOA）预测 1000 名欧洲白人和 1000 名非裔美国人的肾小球滤过率或蛋白尿 兄弟姐妹。 目标 2：确定 >250 个高血压或其相关候选基因中是否存在双等位基因多态性 动脉硬化性脑血管、心脏血管和周围血管并发症（已通过测量 GENOA）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。 目标 3：确定是否存在跨越基因组的 387 个高度多态性串联重复标记位点 （已由 GENOA 测量）与影响肾小球滤过率或白蛋白尿的基因有关 1000 多对欧洲白人兄弟姐妹和 1000 多对非裔美国人兄弟姐妹。