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
Zhang, Tao; Zhang, Huijie; Li, Ying et al. (2017) Long-term Impact of Temporal Sequence from Childhood Obesity to Hyperinsulinemia on Adult Metabolic Syndrome and Diabetes: The Bogalusa Heart Study. Sci Rep 7:43422
Zhang, Huijie; Zhang, Tao; Li, Shengxu et al. (2017) Long-Term Excessive Body Weight and Adult Left Ventricular Hypertrophy Are Linked Through Later-Life Body Size and Blood Pressure: The Bogalusa Heart Study. Circ Res 120:1614-1621
Xi, Bo; Zhang, Tao; Li, Shengxu et al. (2017) Can Pediatric Hypertension Criteria Be Simplified? A Prediction Analysis of Subclinical Cardiovascular Outcomes From the Bogalusa Heart Study. Hypertension 69:691-696
Shen, Wei; Zhang, Tao; Li, Shengxu et al. (2017) Race and Sex Differences of Long-Term Blood Pressure Profiles From Childhood and Adult Hypertension: The Bogalusa Heart Study. Hypertension 70:66-74
Harville, E W; Chen, W; Bazzano, L et al. (2017) Indicators of fetal growth and adult liver enzymes: the Bogalusa Heart Study and the Cardiovascular Risk in Young Finns Study. J Dev Orig Health Dis 8:226-235
Wallace, Maeve; Bazzano, Lydia; Chen, Wei et al. (2017) Maternal childhood cardiometabolic risk factors and pregnancy complications. Ann Epidemiol 27:429-434
Steenstrup, Troels; Kark, Jeremy D; Verhulst, Simon et al. (2017) Telomeres and the natural lifespan limit in humans. Aging (Albany NY) 9:1130-1142
Wang, Fu; Hua, Yingxiao; Whelton, Paul K et al. (2017) Relationship Between Birth Weight and the Double Product in Childhood, Adolescence, and Adulthood (from the Bogalusa Heart Study). Am J Cardiol 120:1016-1019
Aslibekyan, S; Do, A N; Xu, H et al. (2017) CPT1A methylation is associated with plasma adiponectin. Nutr Metab Cardiovasc Dis 27:225-233
Evans, Daniel S; Avery, Christy L; Nalls, Mike A et al. (2016) Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans. Hum Mol Genet 25:4350-4368

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