Molecular Profiling of Diabetes and its Complications

在目前的项目中，正在使用经典流行病学和遗传流行病学的技术来确定2型糖尿病的决定因素、其危险因素及其并发症。 遗传因素的影响在其他项目中进行了评估（DK 069028 -24，糖尿病和肥胖的遗传流行病学和DK 069094 -06，糖尿病并发症的遗传流行病学）;本研究的重点是遗传因素下游的分子过程，如基因转录，蛋白质表达和细胞代谢。 正在凤凰城城市2型糖尿病高危人群中进行纵向研究。 收集适合于RNA提取和蛋白质水平和代谢组学的大规模研究的样品。 收集关于家庭成员的资料，以便纳入以家庭为基础的分析。 最近对骨骼肌组织中全基因组转录的分析表明，少数转录物具有明显的双峰频率分布;其中绝大多数是由转录物编码区域附近的遗传多态性的影响引起的。 与德克萨斯生物医学研究所的研究人员合作，还在外周血样本中测量了大规模的全基因组转录谱。 初步分析显示，大量的转录本与年龄和性别相关，这些数据正在与其他队列的数据进行比较，以进行协作荟萃分析。 目前正在分析外周血样本中的转录与糖尿病、肥胖和相关因素的关系，评估遗传性也是如此。 招募更多的个人和家庭以及纵向跟踪也在进行中。

In the current project, the techniques of classic epidemiology and of genetic epidemiology are being used to identify determinants of type 2 diabetes, its risk factors and its complications. The effects of genetic factors are assessed in other projects (DK069028-24, Genetic Epidemiology of Diabetes and Obesity and DK069094-06, Genetic Epidemiology of Diabetic Complications); the present study focuses on molecular processes that are downstream of genetic factors, such as gene transcription, protein expression and cellular metabolism. Longitudinal studies are being conducted in individuals at high risk for type 2 diabetes in urban Phoenix. Samples are collected that suitable for RNA extraction and for large scale studies of protein levels and metabolomics. Information on family membership is collected for inclusion in family-based analyses. Recent analyses of genome-wide transcription in skeletal muscle tissue have shown that a small number of transcripts have a clearly bimodal frequency distribution; the vast majority of these are accounted for by the effect of a genetic polymorphism in close proximity the region encoding for the transcript. Large scale genome-wide transcription profiles are also being measured in peripheral blood samples in collaboration with investigators from Texas Biomedical Research Institute. Initial analyses have shown a large number of transcripts associated with age and sex, and these data are being compared with those from other cohorts in a collaborative meta-analysis. Analyses of the relationship of transcription in peripheral blood samples with diabetes, obesity and related factors are currently in process, as is the assessment of heritability. Recruitment of additional individuals and families and longitudinal follow-up are also ongoing.