Evolution of Cardiovascular Risk with Normal Aging

描述（由申请人提供）：心血管（C-V）在动脉和心脏结构/功能（CV指数）方面的衰老反映了内在衰老效应、遗传背景中的CV危险因素负担和从生命早期（包括子宫内）开始的环境变化之间复杂的相互作用。这种相互作用是由基因表达调控的，部分由表观遗传机制介导。在Bogalusa心脏研究中，这项更新应用侧重于以社区为基础的黑人白人队列进入中年并自童年以来的这些方面。本研究的具体目的是：1)继续表征儿童时期心脏代谢风险变量的轨迹和家族长寿特征

DESCRIPTION (provided by applicant): 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.