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.

Public Health Relevance

Hypertension, type-2 diabetes, and obesity have a variety of local and systemic manifestations, all of which are likely impacted by a combination of genetic and epigenetic pathways. This study will characterize epigenetic DNA methylation marks important to hypertension, type-2 diabetes, and obesity, and will assess the impact of variation in the expression of key cardiometabolic candidate genes in order to help define the most comprehensive integrative model of cardiometabolic syndrome (CMS). OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01HL130609-03
Application #
9545056
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Papanicolaou, George
Project Start
2016-09-01
Project End
2020-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Thiel de Bocanegra, Heike; Carter-Pokras, Olivia; Ingleby, J David et al. (2018) Addressing refugee health through evidence-based policies: a case study. Ann Epidemiol 28:411-419