OKHSC COBRE: TCF7L2 PROMOTER VARIANTS IN OKLAHOMA AMERICAN INDIANS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 标题：俄克拉何马州印第安人中的TCF7L2启动子变种2型糖尿病是美国日益严重的公共卫生危机。在俄克拉何马州，拥有美国印第安人血统的人被诊断为糖尿病的风险是前者的三倍。在欧洲、中国和中东血统的人群中，TCF7L2和其他基因的变异与糖尿病风险的增加有关，但它们在美洲印第安人糖尿病风险中的作用尚不清楚。我们目前对美国印第安人糖尿病风险的了解主要是基于亚利桑那州的美国印第安人的信息。由于美国印第安人群体之间的遗传、文化和环境差异，俄克拉荷马州的美国印第安人可能存在亚利桑那州人群中没有发现的危险因素。相反，在俄克拉何马州人群中发现的因素可能会导致其他美洲印第安人群体以及整个美国人口患糖尿病的风险。此外，研究样本中超过一半的俄克拉荷马州印第安人至少有一个欧洲血统的祖先，这表明在欧洲人群中与糖尿病风险相关的TCF7L2变异也可能对俄克拉荷马州美国印第安人的糖尿病风险有显著影响。在这项为期一年的先导性研究中，我们正在使用基因测序来确定TCF7L2启动子区域的变异，这些变异可能导致俄克拉荷马州美国印第安人患2型糖尿病的风险。我们的研究使用了以前从96名2型糖尿病患者(192条染色体)中收集的DNA。作为另一项研究的一部分，我们正在评估这些相同个体的TCF7L2基因不同部分(外显子和内含子-外显子边界区域)的多态。测序后，我们将使用统计遗传学方法来推断单倍型，并评估变异之间的连锁不平衡。我们的目标是确定可以用作未来基因特异性关联分析的基础的变异，以及调查基因型与环境交互作用对糖尿病风险的贡献。这项调查的结果可能有助于我们了解糖尿病是如何发展的，从长远来看，可能有助于创建适合文化的糖尿病干预和治疗方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Title: "TCF7L2 promoter variants in Oklahoma American Indians" Type 2 diabetes is a growing public health crisis in the United States. In Oklahoma, having American Indian ancestry triples the risk of being diagnosed with diabetes. Variants in the TCF7L2 and other genes are associated with increased diabetes risk in populations with European, Chinese, and Middle Eastern ancestry, but their role in diabetes risk in American Indians is not well understood. Our current understanding of diabetes risk in American Indians is based largely on information from American Indians in Arizona. Because of genetic, cultural, and environmental differences between American Indian populations, American Indians in Oklahoma may have risk factors not identified in Arizona populations. Conversely, factors identified in Oklahoma groups may contribute to diabetes risk in other American Indian populations, and in the US population as a whole. In addition, more than half of the Oklahoma Indians in the study sample have at least one ancestor of European origin, suggesting that TCF7L2 variants that are associated with diabetes risk in European populations may also contribute significantly to diabetes risk in American Indians in Oklahoma. In this one year pilot study, we are using gene sequencing to identify variants in the TCF7L2 promoter region that potentially contribute to type 2 diabetes risk in American Indians in Oklahoma. Our study uses DNA that was previously collected from 96 individuals (192 chromosomes) with type 2 diabetes. As a part of another study, we are evaluating polymorphisms in a different part of the TCF7L2 gene (the exonic and intron-exon boundary regions) of these same individuals. After sequencing, we will use statistical genetic methods to infer haplotypes and to evaluate linkage disequilibrium between the variants. Our goal is to identify variants that can be used as the basis for future gene-specific association analyses, and for investigations of the contribution of genotype-by-environment interaction effects to diabetes risk. The results of this investigation may help us to understand how diabetes develops, and over the long term are potentially useful for creating culturally-appropriate diabetes interventions and treatments.