OKHSC COBRE: TCF7L2 PROMOTER VARIANTS IN OKLAHOMA AMERICAN INDIANS

OKHSC COBRE：俄克拉荷马州美洲印第安人中的 TCF7L2 启动子变体

• 批准号: 8167971
• 负责人: Diane M Warren
• 金额: $ 7.31万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167971
• 关键词: American Indians; Arizona; Chinese People; Chromosomes; Computer Retrieval of Information on Scientific Projects Database; DNA; Diabetes Mellitus; Diagnosis; Environment; European; Exons; Funding; Future; Genes; Genetic; Genetic Polymorphism; Genotype; Goals; Grant; Haplotypes; Individual; Institution; Intervention; Introns; Investigation; Linkage Disequilibrium; Methods; Non-Insulin-Dependent Diabetes Mellitus; Oklahoma; Pilot Projects; Population; Promoter Regions; Public Health; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling Studies; Source; TCF7L2 gene; United States; United States National Institutes of Health; Variant; base; diabetes risk; promoter

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 标题：“俄克拉荷马州美洲印第安人的TCF 7 L2启动子变体”2型糖尿病是美国日益严重的公共卫生危机。 在俄克拉荷马州，有美洲印第安人血统的人被诊断为糖尿病的风险增加了三倍。 TCF 7 L2和其他基因的变异与欧洲、中国和中东血统人群的糖尿病风险增加有关，但它们在美洲印第安人糖尿病风险中的作用尚不清楚。 我们目前对美洲印第安人糖尿病风险的了解主要基于亚利桑那州美洲印第安人的信息。 由于美洲印第安人群体之间的遗传、文化和环境差异，俄克拉荷马州的美洲印第安人可能具有亚利桑那州人群中未发现的风险因素。 相反，在俄克拉荷马州人群中发现的因素可能会导致其他美洲印第安人人群和整个美国人群的糖尿病风险。 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，这表明与欧洲人群糖尿病风险相关的TCF 7 L2变异也可能对俄克拉荷马州美洲印第安人的糖尿病风险有显著影响。 在这项为期一年的试点研究中，我们正在使用基因测序来识别TCF 7 L2启动子区域的变体，这些变体可能导致俄克拉荷马州美洲印第安人患2型糖尿病的风险。 我们的研究使用了先前从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TCF 7 L2基因不同部分（外显子和内含子-外显子边界区）的多态性。 测序后，我们将使用统计遗传学方法来推断单倍型，并评估变异体之间的连锁不平衡。 我们的目标是确定可以作为未来基因特异性关联分析的基础的变异，以及研究基因型与环境相互作用对糖尿病风险的影响。这项研究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，这对创造适合文化的糖尿病干预和治疗方法可能是有用的。