Epigenomics of Cardiometabolic Diseases in Mexican Americans

 描述(申请人提供)：心脏代谢综合征(CMS)是2型糖尿病(T2D)、高血压(HTN)和肥胖的共同影响，是当今世界面临的最大健康挑战之一。DNA甲基化是在胞嘧啶或腺嘌呤核苷酸上加一个甲基，随年龄和环境暴露而变化，是基因表达的关键表观遗传中介。CMS有多种局部和全身性表现，所有这些都可能受到遗传、基因组和表观遗传途径的影响。我们假设，基因特异性DNA甲基化标记的特征将为CMS的因素提供重要的见解。我们还假设，表征与Abcg1、CPT1A和TXNIP变体相关的DNA甲基化标记可能为调节这些关键的心脏代谢基因提供重要的见解，这些基因以前被确定在CMS中是重要的。因此，该项目的总体目标包括在圣安东尼奥家庭心脏研究(SAFHS)对600名墨西哥美国人的队列中进行的三个具体目标：1)确定基线Abcg1、CPT1A和TXNIP的定量甲基化数据与糖尿病、高血压和肥胖相关的流行表型的关联；2)确定基线Abcg1、CPT1A和TXNIP的定量甲基化数据与四次研究访问中进展为糖尿病、高血压和肥胖的相关性；以及3)整合单核苷酸多态(SNP)变异、甲基化标记和基因表达数据，以确定最全面的CMS因果模型。拟议研究和培训的预期结果是初步数据，以供设计由申请者领导的更大规模的研究，以评估CMS表观遗传学的种族/民族差异。总而言之，这项指导职业发展奖将通过提供获得表观基因组学、健康差距和统计遗传学专业知识的机会，促进候选人作为一名独立科学家的职业发展。(摘要结束)

 DESCRIPTION (provided by applicant): Cardiometabolic syndrome (CMS) is known as the collective impact of type 2 diabetes (T2D), hypertension (HTN), and obesity, and is one of the biggest health challenges facing the world today. DNA methylation, the addition of a methyl group to cytosine or adenine nucleotides, varies with aging and with environmental exposures, and is a critical epigenetic mediator of gene expression. CMS has a variety of local and systemic manifestations, all of which are likely impacted by a combination of genetic, genomic, and epigenetic pathways. We hypothesize that characterization of gene-specific DNA methylation marks will provide important insights into the factors contributing to CMS. We also hypothesize that characterizing DNA methylation marks correlated with ABCG1, CPT1A, and TXNIP variants may provide important insights into the regulation of these key cardiometabolic genes, previously determined to be important in CMS. Thus, the broad goals of this project include three specific aims to be carried out in the San Antonio Family Heart Study (SAFHS) cohort of 600 Mexican Americans: 1) To determine the association of quantitative methylation data from ABCG1, CPT1A, and TXNIP at baseline with prevalent diabetes-, hypertension-, and obesity-related phenotypes; 2) To determine the association of quantitative methylation data from ABCG1, CPT1A, and TXNIP at baseline with progression to diabetes, hypertension, and obesity over four study visits; and 3) To integrate single nucleotide polymorphism (SNP) variation, methylation marks, and gene expression data to define the most comprehensive causal model of CMS. The expected outcome of the proposed research and training is preliminary data to inform the design of a larger study led by the applicant to assess racial/ethnic variation in the epigenetics of CMS. In summary, this Mentored Career Development Award will foster the candidate's professional development as an independent scientist by providing an opportunity to gain expertise in epigenomics, health disparities, and statistical genetics. (End of Abstract)