CANDIDATE GENE RFLPS IN NONINSULIN DEPENDENT DIABETES

糖尿病目前被分类为I型或胰岛素- 依赖型糖尿病(IDDM)和II型或非胰岛素- 依赖型糖尿病(NIDDM)。在美国，那里 大约有500,000例IDDM和500万例NIDDM。 IDDM(人类白细胞抗原基因座)的遗传关联已被证明 6号染色体和胰岛素基因附近的高变区 11号染色体)，但除了一名罕见的胰岛素突变患者 基因，还没有发现类似的遗传关联 NIDDM尽管有很强的家族性。最近，它已经 大多数患者同时存在两种缺陷，这一点已经得到证实 NIDDM患者葡萄糖诱导的胰岛素释放和胰岛素受损 抵抗。 在拟议的研究中，计划利用这一事实 THE：限制性片段长度多态分析 (RFLP)已被证明在解剖 许多疾病的分子基础；具有良好特征的 患者人数是可用的；我们有探测器来检查 在非胰岛素方面可能出现异常的基因数量- 依赖型糖尿病。血液样本将从以下地点获取 NIDDM患者以及非糖尿病患者的特征是 根据它们的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 用多种限制性内切酶和DNA探针 生长因子-II、胰岛素受体、葡萄糖 运输蛋白和其他候选基因 可用。将对数据进行分析，以寻找正相关性 限制性内切酶与胰岛β细胞功能和胰岛素指数的关系 敏感度。在有正相关性的情况下，家族成员 将通过以下方式进行研究，以确认这种联系 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患者潜在的原发缺陷 可用于预测易感性的糖尿病 更重要的是，为了确定未来旨在 阐明了主要缺陷。

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.