ETIOLOGY OF NEPHROPATHY AND HYPERTENSION IN AASK PATIENT

描述（改编自应用程序） 我们将研究大多数高血压和肾病的病因， 在非裔美国人肾脏研究中， 高血压疾病（AASK）。AASK研究是NIH赞助的临床研究。 比较两种水平血压控制效果的多中心试验 三种降压方案对高血压肾病进展的影响 在非裔美国人中。有不成比例的非裔美国人 与高血压靶器官损害，表明遗传易感性， 这一人群;矛盾的是，很少有研究进行评估 这种高风险人群的遗传易感性。的 AASK研究的患者提供了一个独特的机会， 确定高血压的遗传因素和高血压靶点 在高风险和研究不足的人群中发生器官损伤。 拟议中的研究将使患者的白色血细胞永生化， 从这个独特的研究群体中提供可再生的组织和DNA来源， 遵循两种方法评估高血压，肾病， 及其后遗症： 1.研究建议，以确定是否在候选基因的多态性 治疗高血压、肾衰竭和心脏病，包括 肾素-血管紧张素系统基因，胰岛素抵抗（β 3-肾上腺素能受体 和脂蛋白脂酶）基因，利德尔综合征（β和γ ENaC）基因， 其他与高血压或肾衰竭有关， 肾病进展、高血压的严重程度/难治性， 心电图左心室肥大、心血管发病率和 死亡率以及总体发病率和死亡率。 2.进一步的研究将采用一种新的技术，通过混合物连锁作图 不平衡（MALD），它使用最近的连锁不平衡造成的 建立者群体的混合物，以定位与特定的 表型在全基因组筛选中在5-20厘摩区域内。通过 利用微卫星标记，从仔细表型的患者， AASK研究应该可以识别出包含以下内容的感兴趣区域 与高血压、肾衰竭和所述结果相关的基因 上面的候选基因。

DESCRIPTION (adapted from the application) We will study the etiology of hypertension and nephropathy in the majority of the 1094 African-American patients in the African-American Study of Kidney Disease in Hypertension (AASK). The AASK study is an NIH sponsored clinical multicenter trial comparing the effect of two levels of blood pressure control and three antihypertensive regimens on progression of hypertensive nephropathy in African Americans. There is a disproportionate number of African Americans with hypertensive target organ damage, suggesting a genetic susceptibility in this population; paradoxically, few studies have been performed to evaluate such genetic predisposition to disease in this high risk population. The patients of the AASK study offer a unique opportunity to prospectively determine the genetic factors involved in hypertension and hypertensive target organ damage within a high risk and under-studied population. The proposed studies will immortalize white blood cells from patients to provide a renewable source of tissue and DNA from this unique study group, and follow two approaches in assessing the etiology of hypertension, nephropathy, and their sequelae: 1. Studies are proposed to determine whether polymorphisms in candidate genes for hypertension, renal failure, and cardiac disease, including renin-angiotensin system genes, insulin resistance (beta3-adrenergic receptor and lipoprotein lipase) genes, Liddle's syndrome (beta and gammaENaC) genes, and others are related to hypertension or renal failure, severity/rate of progression of renal disease, severity/refractoriness of hypertension, electrocardiographic left ventricular hypertrophy, cardiovascular morbidity and mortality, and overall morbidity and mortality. 2. Additional studies will employ a new technique, mapping by admixture linkage disequilibrium (MALD), which uses the linkage disequilibrium caused by recent admixture of founder populations to localize genes linked to a particular phenotype within a 5-20 centiMorgan region in a genome-wide screen. By utilizing microsatellite markers from the carefully phenotyped patients of the AASK Study it should be possible to identify regions of interest containing genes associated with hypertension, renal failure, and the outcomes described above for candidate genes.