Evolution of Cardiovascular Risk with Normal Aging

正常衰老过程中心血管风险的演变

• 批准号: 8436938
• 负责人: GERALD Sanders BERENSON
• 金额: $ 93.57万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8436938
• 关键词: Adolescent; Adult; Affect; Age; Aging; Aorta; Autopsy; Birth Weight; Black race; Blood specimen; Candidate Disease Gene; Carbon; Cardiac; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Carotid Arteries; Child; Childhood; Clinical; Cohort Studies; Communities; Complex; DNA; DNA Methylation; DNA Modification Process; Data; Dimensions; Elderly; Environmental Risk Factor; Epigenetic Process; Evolution; Fetal Growth; Future; Gender; Gene Expression; Genes; Genetic; Genetic Variation; Genome; Genotype; Growth; Heart; Joints; Left Ventricular Mass; Life; Longevity; Measures; Mediating; Metabolic; Metabolism; Methods; Methylation; Morbidity - disease rate; Myocardial Infarction; Natural History; Outcome; Pattern; Physiologic pulse; Population; Population Study; Predisposing Factor; Prevention; Prevention strategy; Public Health; Race; Regression Analysis; Research; Resources; Risk; Risk Factors; Structure; Testing; Thick; Time; age effect; aged; base; cardiovascular disorder risk; cardiovascular risk factor; cohort; cost effective; developmental plasticity; environmental change; femoral artery; follow-up; gene environment interaction; genome-wide; imprint; in utero; indexing; infancy; intima media; longitudinal database; middle age; mortality; normal aging; trait

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. 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.

描述（由申请人提供）：动脉和心脏结构/功能（CV 指数）方面的心血管（C-V）衰老反映了内在衰老效应、遗传背景中的 CV 危险因素负担以及生命早期（包括子宫内）开始的环境变化之间复杂的相互作用。这种相互作用受基因表达的控制，部分由表观遗传机制介导。该更新应用程序重点关注进入中年的基于社区的黑人白人队列的这些方面，并在 Bogalusa 心脏研究中自童年起进行跟踪。拟议研究的具体目标是：1）继续描述自童年以来心脏代谢风险变量的轨迹以及家庭长寿特征 与动脉和心脏结构/功能（C-V 指数）的关系； 2) 检验出生体重影响成年期 DNA 甲基化（全基因组和候选基因）纵向变化（按种族）的假设； 3) 检验 DNA 甲基化模式（全局和基因特异性）与 12-20 年间测量的 C-V 风险变量之间存在时间关系的假设； 4) 确定整体和基因特异性 DNA 甲基化以及候选基因变异和出生体重对亚临床 C-V 指数的影响。拟议的研究队列由 800 名白人和 550 名黑人无关成年人组成，年龄为 29-52 岁，他们的 C-V 危险因素变量从童年起连续测量 6-15 次、出生体重、成年 C-V 指数、基因型数据（38 个候选基因）和储存的血液样本（基线和随访，间隔 12-20 年）。 C-V指数包括左心室质量和几何重构、颈动脉壁厚度和顺应性；候选基因包括与 C-V 风险、胎儿生长和一碳代谢相关的基因。将使用 Illumina HumanMmethylation450 BeadChip 测量整个基因组和 38 个基因的 DNA 甲基化。多变量回归分析将用于检查出生体重-甲基化、基因-甲基化和甲基化-结果关联。这项研究的结果将进一步了解影响步入中年的混血人群 C-V 老化的诱发因素， 对预防策略有影响。 公共卫生相关性：由遗传和环境因素决定的心脏病发作是全球主要的公共卫生负担；然而，基因与环境相互作用的方面很大程度上是未知的。这项研究的结果将为基因、DNA 修饰和胎儿生长对心血管疾病风险的联合影响提供潜在的解释，并对预防策略产生影响。