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Gene-Specific Responses to Exercise in Discordant Twins

不一致双胞胎对运动的基因特异性反应

基本信息

批准号：
7238877
负责人：
PAUL T WILLIAMS
金额：
$ 67.08万
依托单位：
UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-05-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7238877
关键词：
Accounting Address Affect Apolipoprotein A-I Apolipoprotein A-II Blood Body Weight Canada Candidate Disease Gene Characteristics Class Clinic Controlled Study DNA Data Diet Diet Records Dietary intake Disease regression Environment Enzymes Event Exercise Family Study Food Frequencies Genbank Genes Genetic Genetic Polymorphism Genetic Variation Genotype Haplotypes Health High Density Lipoprotein Cholesterol High Density Lipoproteins Individual Inherited Institution Intake Intra-abdominal Laboratories Linear Regressions Linkage Disequilibrium Mapping Lipids Lipoproteins Low-Density Lipoproteins Measurement Measures Metabolism Modeling Monozygotic Twinning Monozygotic twins Nucleotides Nutrient Performance Pharmacogenetics Phenotype Physical activity Pilot Projects Plasma Positioning Attribute Principal Investigator Proteins Questionnaires Race Recruitment Activity Regulation Reporting Research Running Sampling Selection Bias Source Testing Therapeutic Effect Training Triglycerides Twin Multiple Birth Twin Studies Variant Very Light Exercise Week Weight Woman abdominal fat cost day design experience gel electrophoresis gene environment interaction gene function genetic variant immunoaffinity chromatography knowledge base lipoprotein A-I men particle programs response sedentary size

项目摘要

DESCRIPTION (provided by applicant): As part of the National Runners' Health Study, we have identified 1,350 runners who have an identical (MZ) twin. Our recruitment experience shows that an additional 3,120 MZ twins can be located nationally through Runner's World race participation program. Twenty-eight percent of these MZ twin pairs are expected to be discordant for vigorous exercise (sedentary versus running over 10 miles per week) and otherwise eligible for study. We propose to obtain blood for genotyping, detailed lipoprotein subfraction measurements, clinic weights, and proximal (diet record) and long-term (food frequency questionnaire) nutrient intakes in 400 discordant MZ twin pairs to test whether genes affect the lipoprotein and weight response to vigorous exercise. The analyses assume that the sedentary twin represents (theoretically) the body weight and lipoprotein concentrations of the active twin if he or she were sedentary. We will compare the co-twin lipoprotein and weight differences across genotypes after adjusting for diet. Candidate genes will include SNPs that have been identified by others to affect lipoproteins, weight, propensity to exercise, or that mitigate the responses of lipoproteins to exercise. We will also compare the co-twin phenotype differences to SNPs and haplotypes that linkage disequilibrium maps suggest characterize most of the major genetic variation for genes affecting lipoprotein metabolism. The lipoproteins will include detailed measurements of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subclasses using gradient gel electrophoresis. The individual HDL subclasses will also be analyzed after separating the HDL by immunoaffinity chromatography into particles containing both apo A-I and apo A-II (HDL(A-I with A-II)) and those containing apo A-I and no apo A-II (HDL(A-I without A-II)). The design provides the advantages of both the cross-sectional association studies (large phenotypic effects) and the training studies (controlling for genotype) without the self-selection bias of cross-sectional association studies or the small phenotypic response of training studies. Our first pilot study of 35 pairs of MZ twins revealed a 5.2 mg/dL difference in HDL-cholesterol and a 12 pound weight difference between the active and sedentary twin. By comparison, a major recent training study produced only small average increases in HDL cholesterol (men:l.1 mg/dL; women:l.4 mg/dL) and small decreases in weight (men: 0.9 pounds; women: 0.4 pounds) after 20 weeks of training. The larger effect size of the discordant twin study will provide greater statistical power to detect gene-environment interactions than the training study. DNA samples will be shared with other institutions to cross-validate gene associations identified from training studies or other designs.

描述（由申请人提供）：作为国家跑步者健康研究的一部分，我们已经确定了1,350名拥有同卵（MZ）双胞胎的跑步者。我们的招募经验表明，另外3,120名MZ双胞胎可以通过Runner的世界比赛参与计划在全国范围内找到。这些MZ双胞胎中有28%的人预计不适合剧烈运动（久坐与每周跑步超过10英里），否则就有资格参加研究。我们建议获得血液基因分型，详细的脂蛋白亚组分测量，诊所重量，近端（饮食记录）和长期（食物频率问卷）的营养摄入量在400个不一致的MZ双胞胎对测试基因是否影响脂蛋白和体重反应剧烈运动。分析假设，久坐的双胞胎代表（理论上）的体重和脂蛋白浓度的活跃的双胞胎，如果他或她是久坐的。我们将在调整饮食后比较不同基因型的双胞胎脂蛋白和体重差异。候选基因将包括已被其他人鉴定为影响脂蛋白、体重、运动倾向或减轻脂蛋白对运动的反应的SNP。我们还将比较双胞胎表型差异与连锁不平衡图显示的影响脂蛋白代谢的基因的主要遗传变异特征的SNP和单倍型。脂蛋白将包括使用梯度凝胶电泳对高密度脂蛋白（HDL）和低密度脂蛋白（LDL）亚类的详细测量。在通过免疫亲和色谱法将HDL分离为含有载脂蛋白A-I和载脂蛋白A-II的颗粒（HDL（A-I + A-II））和含有载脂蛋白A-I但不含载脂蛋白A-II的颗粒（HDL（A-I + A-II））后，还将分析单个HDL亚类。该设计提供了横截面关联研究（大的表型效应）和训练研究（控制基因型）的优点，而没有横截面关联研究的自我选择偏倚或训练研究的小表型反应。我们对35对同卵双胞胎进行的第一项初步研究显示，活动和久坐双胞胎之间的HDL胆固醇差异为5.2 mg/dL，体重差异为12磅。相比之下，最近一项主要的训练研究在20周的训练后，HDL胆固醇平均水平仅略有增加（男性：1.1 mg/dL;女性：1.4 mg/dL），体重略有下降（男性：0.9磅;女性：0.4磅）。与训练研究相比，不一致双胞胎研究的较大效应量将提供更大的统计功效来检测基因-环境相互作用。DNA样本将与其他机构共享，以交叉验证从培训研究或其他设计中确定的基因关联。