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HERITAGE FAMILY STUDY, PHASE 4

传统家庭研究，第 4 阶段

基本信息

批准号：
7574400
负责人：
Tuomo Rankinen
金额：
$ 68.63万
依托单位：
LSU PENNINGTON BIOMEDICAL RESEARCH CTR
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-09-01 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7574400
关键词：
Adult Alleles Antithymoglobulin Area Biological Assay Biology Biomedical Research Candidate Disease Gene Code Collaborations Complex Computer Simulation DNA Sequence Data Data Analyses Databases Death Rate Electrophoretic Mobility Shift Assay Elements Exercise Family Family Study Functional RNA Gene Mutation Genes Genetic Heterogeneity Genetic Variation Genomics Goals Haplotypes Heart Rate Heterogeneity Human In Vitro Individual Differences International Intervention Introns Kinesin Life Style Link Lod Score Low Prevalence Luciferases Maps Measurement Messenger RNA Microsatellite Repeats Molecular Monitor Morbidity - disease rate Mutation Noise Nuclear Family Phase Phenotype Physical activity Process Promoter Regions Property Proteins Public Health Quantitative Trait Loci Research Research Design Research Personnel Resources Risk Factors Scanning Screening procedure Signal Transduction Single Nucleotide Polymorphism Subgroup Terminator Codon Testing Training Training Programs Trees Universities Untranslated Regions Variant Washington authority base cardiovascular risk factor cohort connectin design experience fitness gene discovery genetic linkage analysis genome-wide linkage hemodynamics novel optimism positional cloning premature programs promoter protein structure response success tool trait working group

项目摘要

Regular physical activity is associated with a favorable cardiovascular risk factor profile, a lower prevalence of morbidities and reduced premature death rates. However, individual differences are observed in the magnitude of benefits derived from a physically active lifestyle. This phenomenon was investigated in the previous phases of the HERITAGE Family Study in which 742 Blacks and Whites from 214 nuclear families, all adults, completed a standardized and fully monitored 20-week exercise training program. There were large inter-individual differences in responsiveness but this heterogeneity was not randomly distributed, as there was significant familial resemblance in the magnitude of the risk factor responses to the exercise program. These differences in response have been associatedwith a number of candidate genes. Moreover, extensive analyses of the data have made it possible to identify several quantitative trait loci (QTLs) for the responses in important risk factors. In this renewal period (Phase 4; 2005 to 2010), our main goal is to conclude the positional cloning efforts of four QTLs for the response of cardiorespiratory fitness and hemodynamic phenotypes to regular exercise, to resolve them in terms of candidate genes and allelic variants, and to functionally confirm them. Investigators from the Pennington Biomedical Research Center and from Washington University are submitting a single revised application to continue the close collaboration established over the last 12 years in pursuing the proposed positional cloning goals. The hypothesis to be tested in Phase 4 of the HERITAGE Family Study is that human cardiorespiratory fitness and hemodvnamic changes in response to regular exercise are regulated by a minimum of four QTLs. Two of these QTLs have yielded strong candidate genes: titin (TTN; QTL1), and kinesin 5B (KIF5B; QTL2). We propose to finalize the positional cloning efforts of two other QTLs for cardiorespiratory fitness as well as exercise heart rate phenotypes, i.e., QTLS and QTL4 (Specific Aim1). Furthermore, we will continue the ongoing in vitro studies to characterize the functional properties of the alleles of the SNPs that have been associated with the response to regular exercise (Specific Aim 2). This research will generate unique data concerning the biology of adaptation and the molecular basis of human heterogeneity in the responsiveness to regular exercise. Studies designed to understand why some people are fundamentally more likely to benefit from a physically active lifestyle than others are very important as such a lifestyle is recommended by all national and international public health authorities.

规律的身体活动与良好的心血管危险因素相关，患病率较低