Evolution of Cardiovascular Risk with Normal Aging

正常衰老过程中心血管风险的演变

基本信息

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
项目类别：
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

项目摘要

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）：在动脉和心脏结构/功能（CV指数）方面，心血管（C-V）老化反映了内在的老化效应，在早期生活（包括UTERO）开始的遗传背景和环境变化中CV风险因素的负担，CV风险因素的负担。该相互作用由表观遗传机制部分介导的基因表达控制。这种更新的应用集中在一个基于社区的黑白队列中的中年生活中，并在Bogalusa Heart研究中随之而来。拟议的研究的具体目的是：1）继续表征自童年以来心脏代谢风险变量的轨迹和家族寿命特征与动脉和心脏结构/功能（C-V指数）有关； 2）测试假设的出生体重会影响成年期间DNA甲基化（全基因组和候选基因）的纵向变化； 3）检验以下假设：DNA甲基化模式（全球和基因特异性）与在12 - 20年内测得的C-V风险变量之间存在时间关系； 4）确定全球和基因特异性DNA甲基化与候选基因变体以及出生权重对亚临床C-V指数的影响。拟议的研究队列由800名白色和550名黑人无关的成年人组成，年龄在29-52岁之间，他们的C-V风险因素变量从儿童期，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（基线和后续生物和后续时间）（分别为12-20年），串行6-15次。 C-V指数包括左心室质量和几何重塑，颈动脉壁的厚度和依从性；候选基因包括与C-V风险，胎儿生长和单碳代谢有关的基因。将使用Illumina Human -Methylation 450 Beadchip测量整个基因组的DNA甲基化和38个基因。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。这项研究的发现将进一步了解影响混血中的C-V衰老的诱发因素，该血统群体达到中年，这对预防策略有影响。公共卫生相关性：由遗传和环境因素决定的心脏病发作代表了全球的主要公共卫生负担；但是，基因环境相互作用的方面在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共同影响提供潜在的解释，并对预防策略产生影响。