Epigenomics of Cardiometabolic Diseases in Mexican Americans

 描述（由申请人提供）：心脏代谢综合征（CMS）被认为是2型糖尿病（T2 D）、高血压（HTN）和肥胖的综合影响，是当今世界面临的最大健康挑战之一。DNA甲基化，甲基基团添加到胞嘧啶或腺嘌呤核苷酸，随着年龄和环境暴露而变化，并且是基因表达的关键表观遗传介质。CMS具有多种局部和全身表现，所有这些都可能受到遗传、基因组和表观遗传途径的组合的影响。我们假设，基因特异性DNA甲基化标记的表征将提供重要的见解的因素，有助于CMS。我们还假设，表征与ABCG 1，CPT 1A和TXNIP变体相关的DNA甲基化标记可能为这些关键心脏代谢基因的调控提供重要的见解，这些基因先前被确定为在CMS中很重要。因此，该项目的广泛目标包括在600名墨西哥裔美国人的圣安东尼奥家庭心脏研究（SAFHS）队列中进行的三个具体目标：1）确定基线时来自ABCG 1、CPT 1A和TXNIP的定量甲基化数据与流行的糖尿病、高血压和肥胖相关表型的关联; 2）确定在基线时来自ABCG 1、CPT 1A和TXNIP的定量甲基化数据与在四次研究访问中进展为糖尿病、高血压和肥胖的相关性;整合单核苷酸多态性（SNP）变异、甲基化标记和基因表达数据，以定义CMS最全面的因果模型。拟议的研究和培训的预期成果是初步数据，以告知由申请人领导的更大研究的设计，以评估CMS表观遗传学中的种族/民族变异。总之，这个指导职业发展奖将通过提供获得表观基因组学，健康差异和统计遗传学专业知识的机会，促进候选人作为独立科学家的专业发展。(End摘要）

 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)