OKHSC COBRE: GENETIC AND ENVIRONMENTAL CONTRIB TO DIABETES IN 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。 2型糖尿病的特征是胰岛素抵抗、胰岛素分泌受损和高血糖。俄克拉荷马州美国印第安人的年龄调整糖尿病患病率是白人的三倍，糖尿病相关死亡率是白人的1.8倍。遗传因素和环境因素都被认为是 是造成这种差距的根本原因。本项目调查了影响俄克拉荷马州美洲印第安人14种糖尿病相关表型的遗传因素、环境因素和基因与环境交互作用效应：空腹和2小时血糖浓度、空腹和2小时血清胰岛素浓度、 血清甘油三酯水平；高密度脂蛋白胆固醇浓度；收缩和舒张压；糖尿病发病年龄；体重指数；腰臀比；以及纤维蛋白原、PAI-1和C反应蛋白水平。表型数据将从184对受影响的成人同胞的医疗记录中收集。年龄，性别，血统， 饮食、活动和其他环境数据将来自医疗记录和调查问卷。将对SIB对及其一级亲属(用于根据州建立等位基因同一性)进行6000个单核苷酸多态(SNPs)的基因分型。其目的是使用基于方差分量的统计遗传学方法来定位导致表型变异的遗传因素，并调查遗传效应因环境而异的程度。具体目的是：1)使用数量遗传学方法估计相加的遗传和测量的环境协变量对14对美国印第安人兄弟姐妹中糖尿病相关表型变异的贡献；2)使用数量遗传学方法检查 3)使用全基因组多点连锁分析来检测与高信息量常染色体SNP标记所代表的染色体区域的表型连锁的证据。长期目标是确定遗传和环境因素在开发文化上适当的干预和治疗方面的潜在用途。相关性：俄克拉何马州美洲印第安人社区2型糖尿病的高患病率构成了一个主要的公共卫生问题 危机。确定糖尿病风险的遗传和环境因素对于制定有效的、文化上适当的干预和治疗策略是必要的。

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. Type 2 diabetes is characterized by insulin resistance, impaired insulin secretion, and hyperglycemia. Oklahoma American Indians have an age-adjusted diabetes prevalence three times that of whites, and a diabetes-related death rate 1.8 times that of whites. Both genetic and environmental factors are suggested to underlie this disparity. This project investigates the genetic factors, environmental factors, and genotype by environment interaction effects influencing 14 diabetes-related phenotypes in Oklahoma American Indians: fasting and 2-hour plasma glucose concentrations; fasting and 2-hour serum insulin concentrations; serum triglyceride level; HDL cholesterol concentration; systolic and diastolic blood pressure; age of diabetes onset; body mass index; waist-to-hip ratio; and levels of fibrinogen, PAI-1, and C-reactive protein. Phenotype data will be collected from medical records of 184 adult, affected sib pairs. Age, sex, ancestry, diet, activity, and other environmental data will be taken from medical records and questionnaires. Sib pairs and their first degree relatives (used to establish allelic identity by state) will be genotyped for 6000 single nucleotide polymorphisms (SNPs). The objective is to use variance components-based statistical genetics methods to localize genetic factors that contribute to phenotype variation, and to investigate the extent to which genetic effects vary by environment. The specific aims are to: 1) use quantitative genetics methods to estimate the contribution of additive genetic and measured environmental covariates to variation in 14 diabetes-related phenotypes in American Indian sib pairs; 2) use quantitative genetics methods to examine genotype-by-environment interaction effects influencing the phenotypes; and 3) use genome-wide multipoint linkage analyses to detect evidence of phenotype linkage to chromosomal regions represented by highly informative autosomal SNP markers. The long-term goal is to identify genetic and environmental factors of potential use in developing culturally appropriate interventions and treatments. Relevance: The high prevalence of type 2 diabetes in American Indian communities in Oklahoma constitutes a major public health crisis. The identification of genetic and environmental components of diabetes risk is necessary to the development of effective, culturally-appropriate intervention and treatment strategies.