GENETIC EPIDEMIOLOGY OF NIDDM IN A HISPANIC COMMUNITY

西班牙裔社区 NIDDM 的遗传流行病学

• 批准号: 2870322
• 负责人: Christopher E. ASTON
• 金额: $ 0.96万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-17 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2870322
• 关键词: Hispanic Americans; alleles; blood chemistry; diabetes mellitus genetics; disease /disorder onset; disease /disorder proneness /risk; epidemiology; family genetics; genetic markers; genetic polymorphism; genotype; glucose tolerance test; human genetic material tag; human subject; linkage mapping; noninsulin dependent diabetes mellitus; phenotype; polymerase chain reaction; questionnaires; statistics /biometry

The study proposed will identify genes involved in predisposing to non- insulin dependent diabetes mellitus (NIDDM). The target population is Hispanic, a minority group known to have a higher prevalence of diabetes (10-15 %) than in most Caucasians (2-4%). We will use two approaches to detecting linkage between the NIDDM phenotype and a number of candidate marker loci. In combination, these two methods promise a high probability of success under a number of possible hypothesized models for the NIDDM phenotype. First, we will ascertain 200 affected-sib-pairs and use the sib-pair identity-by-descent method of analysis. The main strength of this method is that it is non-parametric, that is, no model for the mode of inheritance of the NIDDM phenotype is required, thus avoiding problems of delayed age-of-onset and lack of penetrance. Furthermore, the sib-pair analysis has the potential to identify multiple loci that may determine the NIDDM phenotype. Second, we will ascertain 25 large (20-25 member), multiplex families and use classical linkage analysis to detect linkage separately within each family. The main strength of this method is that by restriction to a single family at a time for analysis, we should avoid heterogeneity in the NIDDM phenotype, if such heterogeneity exists. We will use epidemiological and clinical data on, for example, age-at-onset, presence of hyperinsulinemia or insulin resistance in the families of our probands to classify subsets of NIDDM which can be formally tested for heterogeneity. We will examine a large number of genes which can be considered candidate genes for NIDDM because of their biochemical role in glucose homeostasis and genes which have been previously reported to be associated with NIDDM. More important to the proposed study is the fact that for each of the candidate genes, we will use as markers short tandem repeat, microsatellite, polymorphisms which are highly informative, average heterozygosity equal to or less than 0.7, and are easily typed by DNA amplification using the polymerase chain reaction (PCR) to maximize the amount of genetic information extracted from our sample of relatives. We will take advantage of a long-term study of the Hispanic population of the San Luis Valley of Southern Colorado in which the epidemiologic characteristics of NIDDM have been well documented, and where the elevated prevalence of NIDDM has allowed us to identify a large cohort of affected sib-pairs and large, multigenerational families.

提出的研究将确定涉及倾向于非 - 的基因 胰岛素依赖性糖尿病（NIDDM）。目标人群是 西班牙裔，少数群体已知糖尿病患病率更高 （10-15％）比大多数高加索人（2-4％）。我们将使用两种方法 检测NIDDM表型与许多候选人之间的联系 标记基因座。结合使用，这两种方法有望很高 在许多可能的假设模型下成功的概率 对于NIDDM表型。首先，我们将确定200个受影响的SIB对 并使用分析的SIB对身份分析方法。主 这种方法的强度是它是非参数的，也就是说，没有模型 对于NIDDM表型的遗传方式，因此需要 避免发病年龄延迟和缺乏外渗的问题。 此外，SIB-PAIR分析有可能识别 可以决定NIDDM表型的多个基因座。第二，我们会的 确定25个大型（20-25个成员），多路复用家庭并使用经典 链接分析以分别检测每个家庭中的联系。这 这种方法的主要优势是，通过限制一个家庭 在一个分析时，我们应该避免NIDDM中的异质性 如果存在这种异质性，则表型。我们将使用流行病学和 例如，临床数据，例如年龄，存在 我们的概率家族中的高胰岛素血症或胰岛素抵抗 为NIDDM的子集进行分类，可以正式测试 异质性。我们将检查大量的基因 由于其生化作用而被认为是NIDDM的候选基因 在葡萄糖稳态和基因中，以前已报道 与NIDDM相关联。对于拟议的研究而言，更重要的是 事实，对于每个候选基因，我们都将用作标记短 串联重复，微卫星，多态性高度 信息丰富的平均杂合性等于或小于0.7，是 使用聚合酶链反应很容易通过DNA扩增键入 （PCR）最大化从我们的遗传信息量 亲戚样本。我们将利用长期研究 科罗拉多州圣路易斯谷的西班牙裔人口 NIDDM的流行病学特征已经有充分的文献记载， NIDDM的升高率使我们能够识别 大量受影响的SIB对和大型多代 家庭。