IDENTIFICATION OF GENETIC MARKERS FOR FOCAL SEGMENTAL GLOMERULOSCLEROSIS

局灶节段性肾小球硬化症遗传标记的鉴定

• 批准号: 2463820
• 负责人: C A WINKLER
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2463820
• 关键词: African American; HIV infections; disease /disorder proneness /risk; genetic mapping; genetic markers; glomerulosclerosis; histocompatibility gene; human genetic material tag; human population genetics; racial /ethnic difference

Focal segmental glomerulosclerosis (FSGS) is a chronic renal disease seen both in idiopathic form and in association with HIV infection, heroin use, and sickle cell anemia, but always with a higher prevalence in black populations. FSGS represents a morphologic response to renal injury, but the increased prevalence of FSGS in blacks suggests a genetic component may underlie this predisposition to FSGS. We are currently establishing lymphoblastoid cell lines from three groups of patients for a genetic analysis using 300 microsatellite markers. The patient groups are: (1) 100 black patients with FSGS but without HIV infection, (2) 100 black patients with HIV associated FSGS, (3) and a control group of 200 HIV seropositive black patients without evidence of clinical renal disease. HLA loci will be detected by molecular methods and approximately 300 microsatellite markers will be tested for use in mapping by admixture disequilibrium analysis. In addition, specific candidate genes will be screened using single strand conformational and restriction fragment length polymorphisms to detect associations between specific alleles and disease category. If anonymous markers show an association with FSGS, the genomic region will be examined for the presence of additional markers that can be analyzed and for specific candidate genes located in the region of interest.

局灶节段性肾小球硬化(FSGS)是一种慢性肾脏疾病 既有特发性的，也有与艾滋病毒感染有关的， 海洛因使用和镰状细胞性贫血，但患病率总是较高 在黑人人口中。FSGS代表对肾脏的一种形态反应 伤害，但FSGS在黑人中的患病率增加表明 遗传成分可能是这种FSGS易感性的基础。我们是 目前正在建立的淋巴母细胞系来自三组 使用300个微卫星标记对患者进行遗传分析。这个 患者组为：(1)100名患有FSGS但未感染HIV的黑人患者 感染，(2)100名感染艾滋病毒相关FSGS的黑人患者，(3)和 对照组200例无证据的HIV血清阳性黑人患者 临床肾脏疾病。人类白细胞抗原基因座将由分子检测 方法和大约300个微卫星标记将被测试 在混合不平衡分析成图中的应用。此外, 将使用单链筛选特定的候选基因 检测构象和限制性片段长度多态 特定等位基因与疾病类别之间的关联。如果 匿名标记显示与基因组区域FSGS有关 将检查是否存在其他标记，这些标记可以 对位于区域的特定候选基因进行分析 利息。