Project 4 - Cardiovascular domain

项目4-心血管领域

基本信息

批准号：
9070465
负责人：
Hao Mei
金额：
$ 29.87万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至 2017-06-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9070465
关键词：
3&apos Flanking Region Accounting Age Aging Alcohol consumption Biological Aging Biological Markers Blood Flow Velocity Blood Vessels Candidate Disease Gene Cardiovascular Diseases Cardiovascular system Cause of Death Childhood Chromosomes Clinical Complement Data Elderly Event Exons Exposure to Genes Genetic Genetic Determinism Genetic Predisposition to Disease Genomic Segment Genomics Genotype Grouping Haplotypes Heart Heritability Impairment Indium Individual Instruction Length Leukocytes Life Link Literature Louisiana Measures Mentors Methods Natural regeneration Nonagenarian Obesity Participant Phenotype Physiologic pulse Population Growth Public Health Publishing Pulse Pressure RNA Splicing Regenerative Medicine Research Sampling Sampling Studies Scanning Signal Transduction Site Stem cells Structure Testing Time Tobacco smoke Variant Vascular remodeling age related arterial stiffness cohort early childhood follow-up genetic association genetic variant genome-wide linkage healthy aging human old age (65+)indexing intimal medial thickening lifestyle factors mortality non-genetic population based prevent rare variant telomere

项目摘要

Vascular aging (VA) is the progressive vascular remodeling and alteration of vascular structure that accompanies biological aging. VA results in an increase in artery stiffness, accompanied by impairment of endothelial regeneration and shortening of leukocyte telomere length (LTL). The progress of VA in early age strongly predicts the occurrence of CVD, the leading cause of death in old age. This progress is determined in part by genetic factors, with effects modifiable by exposure to various non-genetic factors. The overall objective of this proposal is to identify genetic components with modest-to-large longitudinal effects on the progress of VA from childhood, and to investigate the association of genetic components with circulating endothelial progenitor cells (EPCs) and leukocyte telomere length (LTL) that represent endothelial regeneration and biological aging respectively. Our specific aims are to: (1) Identify genomic linkage regions and candidate genes underlying VA. The hypotheses are that one or more chromosome regions exert modest-to-large, heritable genetic effects on VA phenotypes from early childhood, and that some candidate genes exert modest-to-large effects but lack detectable heritability. (2) Determine common and rare effect variants at the genomic linkage regions and candidate genes identified in Specific Aim 1 that are associated with VA, endothelial regeneration and biological aging. The hypotheses are that genetic determinants underlying VA phenotypes are related to circulating EPCs and LTL, and rare functional variants in five important candidate genes are associated with longitudinal VA phenotypes in the upper and lower 5% of BHS participants. (3) Validate significant findings from Specific Aim 2 in a replication sample. The hypothesis is that the findings of common and rare effect variants will be repeated in a random populationbased sample and are associated with healthy aging. It is expected that identification of effect variants underlying VA will be important for defining genetic predisposition to vascular aging or healthy aging later in life.

血管老化（VA）是进行性血管重塑和血管结构的改变伴随着生物衰老。 VA导致动脉刚度的增加，伴随着损害白细胞端粒长度（LTL）的内皮再生和缩短。 VA早期的进展强烈预测CVD的发生，CVD是老年死亡的主要原因。确定了这个进度部分由遗传因素，通过暴露于各种非遗传因素来改变的效果。总体该提案的目的是确定对纵向纵向影响的遗传成分对 VA从童年的进步，并研究遗传成分与循环的关联内皮祖细胞（EPC）和白细胞端粒长度（LTL），代表内皮再生和生物衰老。我们的具体目的是：（1）确定基因组链接区域和候选基因VA。假设是一个或多个染色体区域施加从小就对VA表型对VA表型的谦虚，可遗传的遗传作用，而某些候选人基因发挥适中的影响，但缺乏可检测到的遗传力。（2）确定常见和罕见效果在特定目标1中鉴定的基因组联系区域和候选基因的变体与相关的特定目标1 随着VA，内皮再生和生物衰老。假设是遗传决定因素潜在的VA表型与循环EPC和LTL有关，五个功能变体重要的候选基因与上和下5％的纵向VA表型有关 BHS参与者。（3）在复制样本中验证特定目标2的显着发现。这假设是，将在基于人群的随机种群中重复常见和稀有效应变体的发现样本，与健康衰老有关。预计效果变体的识别基础VA对于确定对血管衰老或健康衰老的遗传易感性很重要生活。