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: 3876142
• 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/3876142
• 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.

糖尿病目前被分为I型或胰岛素- 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， 约有50万例胰岛素依赖型糖尿病和500万例非胰岛素依赖型糖尿病。 已经显示出与IDDM的遗传关联（ 6号染色体和胰岛素基因附近的高变区 11号染色体），但除了一个罕见的病人与突变的胰岛素 基因，没有发现类似的遗传关联， NIDDM尽管它有很强的家族性。 近来这个字 在大多数患者中，两种缺陷共存已得到证实 NIDDM患者，葡萄糖诱导的胰岛素释放受损， 阻力 在拟议的研究中，计划利用这一事实， 限制性片段长度多态性分析 （RFLP）已被证明是强大的解剖 许多疾病的分子基础; 患者人群是可用的;我们有探针来检查 非胰岛素异常的候选基因数量 依赖性糖尿病 血液样本将从 NIDDM患者以及非糖尿病患者， 基于它们的β细胞分泌能力和它们的 胰岛素敏感性 从白细胞中分离的DNA将被切割 用各种限制性内切酶和DNA探针 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， available. 将分析数据的正相关性 RFLPs与β细胞功能和胰岛素指数之间 灵敏度 在具有正相关性的病例中， 将进行研究，以确认通过 连锁不平衡 因此，这些研究表明， 检测非胰岛素依赖型糖尿病的潜在原发性缺陷 可能有助于预测易感性的糖尿病 更重要的是确定未来的研究， 阐明主要缺陷。