CANDIDATE GENE RFLPS IN NONINSULIN DEPENDENT DIABETES

非胰岛素依赖型糖尿病中的候选基因 RFLPS

• 批准号: 3897563
• 负责人: JOHN KARAM
• 金额: --
• 依托单位: MOUNT ZION HOSPITAL AND MEDICAL CENTER
• 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/3897563
• 关键词: DNA; biological polymorphism; diabetes mellitus; endonuclease; gel electrophoresis; genes; genetic mapping; glucose tolerance test; glucose transport; hormone regulation /control mechanism; human population genetics; human subject; insulin; insulin receptor; insulinlike factor; intravenous administration; linkage mapping; molecular pathology; noninsulin dependent diabetes mellitus; nucleic acid hybridization; nucleic acid probes; pancreatic islet function; pancreatic islets; protein transport

Diabetes mellitus is currently classified into Type I or insulin- dependent diabetes mellitus (IDDM) and Type II or noninsulin- dependent diabetes mellitus (NIDDM). In the United States there are approximately 500,000 cases of IDDM and 5,000,000 with NIDDM. Genetic association has been shown for IDDM (the HLA locus on Chromosome 6 and the hypervariable region near the insulin gene on chromosome 11) but except for a rare patient with a mutant insulin gene, there have been no similar genetic associations found for NIDDM despite its very strong familial nature. Recently it has become well-established that two defects coexist in most patients with NIDDM, impaired glucose-induced insulin release and insulin resistance. In the proposed studies it is planned to take advantage of the fact that: analysis of restriction fragment length polymorphisms (RFLPs) have been demonstrated to be powerful in dissecting the molecular basis for a number of diseases; a well characterized patient population is available; and we have probes to examine a number of genes that are candidates to be abnormal in noninsulin- dependent diabetes mellitus. Blood samples will be obtained from patients with NIDDM as well as nondiabetics who are characterized on the basis of their beta cell secretory capacity and their insulin sensitivity. DNA isolated from leukocytes will be cleaved with a variety of restriction endonucleases and probed with DNA growth factor-II (IGF-II), the insulin receptor, the glucose transport protein, and other candidate genes as they become available. The data will be analyzed for positive correlations between the RFLPs and indices of beta cell function and insulin sensitivity. In cases having positive correlations familial studies will be performed to confirm the association through linkage disequilibrium. These studies therefore show promise for detecting potential primary defects in noninsulin-dependent diabetes mellitus that could be useful in predicting susceptibility and more importantly for determining future studies aimed at elucidating the primary defects.

糖尿病目前分为 I ​​型或胰岛素型糖尿病 依赖性糖尿病 (IDDM) 和 II 型或非胰岛素- 依赖性糖尿病（NIDDM）。 在美国有 大约有 500,000 例 IDDM 病例和 5,000,000 例 NIDDM 病例。 IDDM 的遗传关联已被证明（HLA 位点 6号染色体和胰岛素基因附近的高变区 11 号染色体），但罕见的胰岛素突变患者除外 基因，尚未发现类似的遗传关联 尽管 NIDDM 具有很强的家族性。 最近有 已明确大多数患者同时存在两种缺陷 NIDDM、葡萄糖诱导的胰岛素释放受损和胰岛素 反抗。 在拟议的研究中，计划利用这一事实 that：限制性片段长度多态性分析 （RFLP）已被证明在剖析 许多疾病的分子基础；具有良好特征的 可获得患者群体；我们有探针来检查 非胰岛素异常候选基因的数量 依赖性糖尿病。 血液样本将来自 NIDDM 患者以及具有以下特征的非糖尿病患者 根据其 β 细胞分泌能力及其 胰岛素敏感性。 从白细胞中分离的 DNA 将被切割 使用多种限制性内切酶并用 DNA 进行探测 生长因子-II (IGF-II)、胰岛素受体、葡萄糖 转运蛋白和其他候选基因 可用的。 将分析数据的正相关性 RFLP 与 β 细胞功能指数和胰岛素之间的关系 敏感性。 如果与家族呈正相关 将进行研究以确认这种关联 连锁不平衡。 因此，这些研究表明有希望 检测非胰岛素依赖型患者潜在的主要缺陷 糖尿病可能有助于预测易感性 更重要的是确定未来的研究目标 阐明主要缺陷。