ETIOLOGY OF NEPHROPATHY AND HYPERTENSION IN AASK PATIENT

说明(改编自应用程序) 我们将研究高血压和肾病的病因。 非裔美国人肾脏研究中的1094名非裔美国人患者 高血压病(AASK)。AASK研究是由美国国立卫生研究院赞助的临床研究 两种水平血压控制效果的多中心试验比较 三种降压方案对高血压肾病进展的影响 在非裔美国人身上。非洲裔美国人的数量不成比例 有高血压靶器官损害，表明遗传易感性 这一群体；矛盾的是，很少有人进行研究来评估 在这个高危人群中对疾病的遗传易感性。这个 AASK研究的患者提供了一个独特的机会来前瞻性地 确定与高血压有关的遗传因素和高血压目标 高危和研究不足的人群中的器官损伤。 拟议中的研究将使患者的白细胞永生 从这个独特的研究小组提供可再生的组织和DNA来源，以及 遵循两种方法评估高血压、肾病、 以及他们的后遗症： 1.建议进行研究，以确定候选基因的多态 用于高血压、肾功能衰竭和心脏病，包括 肾素-血管紧张素系统基因与胰岛素抵抗(β3-肾上腺素能受体 和脂蛋白脂酶)基因，利德尔综合征(β和GammaENaC)基因， 其他与高血压或肾功能衰竭有关，严重程度/比率 肾脏疾病进展、高血压的严重程度/难治性、 心电图左室肥厚、心血管并发症及 死亡率，以及总体发病率和死亡率。 2.其他研究将采用一种新技术--混合连锁作图 不平衡(MALD)，它使用由最近的 混合创始人群体以定位与特定基因相关的基因 在全基因组筛选中的5-20 centiMorgan区域内的表型。通过 利用细心分型的非霍奇金淋巴瘤患者的微卫星标记 AASK研究应该可以确定包含以下内容的感兴趣区域 与高血压、肾功能衰竭相关的基因和所描述的结果 上面是候选基因。

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.