The cardiovascular (C-V) aging in terms of arterial and cardiac structure/function (CV indices) reflects complex interplay between the intrinsic aging effect, burden of CV risk factors in a genetic background and environmental changes beginning in early life, including in utero. This interplay is governed by gene expression mediated in part by epigenetic mechanisms. This renewal application focuses on these aspects in a community-based, black white cohort entering midlife and followed since childhood in the Bogalusa Heart Study.
The Specific Aims of the proposed research are: 1) to continue characterizing the trajectories of cardio-metabolic risk variables since childhood and the familial longevity trait in relation to the arterial and cardiac structure/function (C-V indices);2) to test the hypothesis tht birth weight affects longitudinal changes of DNA methylation (genome-wide and in candidate genes) during adulthood by race;3) to test the hypothesis that there is a temporal relationship between DNA methylation patterns (global and gene-specific) and C-V risk variables measured over 12-20 years;and 4) to determine effect of global and gene-specific DNA methylation in conjunction with candidate gene variants and birth weight on subclinical C-V indices. The proposed study cohort consists of 800 white and 550 black unrelated adults, aged 29-52 years, who have C-V risk factor variables measured serially 6-15 times from childhood, birth weight, adulthood C-V indices, genotype data (38 candidate genes) and stored blood samples (baseline and follow-up, 12-20 years apart). The C-V indices include left ventricular mass and geometric remodeling, carotid artery wall thickness and compliance;candidate genes include those related to C-V risk, fetal growth and one-carbon metabolism. DNA methylation will be measured for the whole genome and 38 genes using Illumina HumanMethylation450 BeadChip. Multivariable regression analyses will be used to examine the birth weight-methylation, gene-methylation and methylation-outcome associations. Findings from this research will further the understanding of the predisposing factors that influence C-V aging in a biracial population reaching mid-life, which have implications for preventive strategies.

Public Health Relevance

Heart attack determined by genetic and environmental factors represents a major public health burden worldwide;however, the aspect of the gene-environment interaction is largely unknown. Findings from this study will provide a potential explanation for the joint impact of genes, DNA modifications and fetal growth on cardiovascular disease risk and have implications in prevention strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG016592-12A1
Application #
8436938
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Rossi, Winifred K
Project Start
2012-09-30
Project End
2016-08-31
Budget Start
2012-09-30
Budget End
2013-08-31
Support Year
12
Fiscal Year
2012
Total Cost
$935,739
Indirect Cost
$287,859
Name
Tulane University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Das, Mithun; Sha, Jin; Hidalgo, Bertha et al. (2016) Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. PLoS One 11:e0145789
Mzayek, Fawaz; Cruickshank, J Kennedy; Amoah, Doris et al. (2016) Birth weight was longitudinally associated with cardiometabolic risk markers in mid-adulthood. Ann Epidemiol 26:643-7
Chen, Wei; Li, Shengxu; Fernandez, Camilo et al. (2016) Temporal Relationship Between Elevated Blood Pressure and Arterial Stiffening Among Middle-Aged Black and White Adults: The Bogalusa Heart Study. Am J Epidemiol 183:599-608
Bazzano, L A; Hu, T; Bertisch, S M et al. (2016) Childhood obesity patterns and relation to middle-age sleep apnoea risk: the Bogalusa Heart Study. Pediatr Obes :
Jacobs, M B; Harville, E W; Kelly, T N et al. (2016) Maternal apolipoprotein E genotype as a potential risk factor for poor birth outcomes: The Bogalusa Heart Study. J Perinatol 36:432-8
Zhang, Tao; Zhang, Huijie; Li, Shengxu et al. (2016) Impact of Adiposity on Incident Hypertension Is Modified by Insulin Resistance in Adults: Longitudinal Observation From the Bogalusa Heart Study. Hypertension 67:56-62
Harville, Emily W; Jacobs, Marni B; Qi, Lu et al. (2016) Multigenerational Cardiometabolic Risk as a Predictor of Birth Outcomes: The Bogalusa Heart Study. J Pediatr :
Zhang, Tao; Zhang, Huijie; Li, Ying et al. (2016) Temporal Relationship Between Childhood Body Mass Index and Insulin and Its Impact on Adult Hypertension: The Bogalusa Heart Study. Hypertension 68:818-23
O'Neil, C E; Nicklas, T A; Liu, Y et al. (2015) Candy consumption in childhood is not predictive of weight, adiposity measures or cardiovascular risk factors in young adults: the Bogalusa Heart Study. J Hum Nutr Diet 28 Suppl 2:59-69
Chen, Wei; Yun, Miaoying; Fernandez, Camilo et al. (2015) Secondhand smoke exposure is associated with increased carotid artery intima-media thickness: the Bogalusa Heart Study. Atherosclerosis 240:374-9

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