Heritage Study--Genetics, Exercise and Risk Factors

Cardiovascular Diseases, Diabetes Mellitus, Diabetes Mellitus, Non-insulin Dependent, Heart Diseases

To document the role of the genotype in the cardiovascular and metabolic responses to aerobic exercise-training and the contribution of inherited factors in the changes brought about by regular exercise for several cardiovascular disease and diabetes risk factors. A consortium of laboratories from five institutions in the United States and Canada are carrying out this study.

BACKGROUND: This research should increase our understanding of human variation, the genetics of adaptation to exercise-training and of the concomitant changes in cardiovascular disease and diabetes risk factors. DESIGN NARRATIVE: A total of 742 sedentary subjects were recruited, initially tested, exercise-trained in the laboratory with the same program for 20 weeks, and re-tested. The subjects came from families of Caucasian descent with both parents and three biological adult offspring and families of African-American ancestry. Oxygen uptake, expiratory volume and respiratory exchange ratio, blood pressure, heart rate, blood lactate, glucose, glycerol and free-fatty acids, stroke volume and cardiac output were measured during exercise before and after training and maximal oxygen uptake was determined. Plasma lipids, lipoproteins and apoproteins, glucose tolerance and insulin response to an intravenous glucose load, plasma sex steroids and glucocorticoids, resting systolic and diastolic blood pressures, and body fat and regional fat distribution were also assessed. Dietary habits, level of habitual physical activity and other lifestyle components were assessed by questionnaires. Genetic analyses included the determination of the heritability level for each phenotype and its response to regular exercise, testing for the presence of paternal or maternal effects, sex-limited effects, major gene effects and segregation patterns. Multivariate genetic analyses and complex segregation analyses were used to develop hypotheses concerning the genetic basis of the response to exercise-training. The study was renewed in September 1997 to perform analyses of the data collected under Phase I. A series of nongenetic studies were undertaken on the dataset. Physiological, behavioral, and social determinants of maximal and submaximal indicators of cardiorespiratory endurance in the sedentary state and in the response to training were investigated taking into account the contributions of age, gender, and race. Similar analyses were conducted on the cardiovascular disease and non-insulin dependent diabetes mellitus (NIDDM) risk factors monitored in the study. Genetic analyses determined the heritability levels and tested for paternal or maternal effects, major gene effects, and segregation patterns which were used to develop hypotheses concerning genetic bases of the response to endurance exercise. A panel of candidate genes were typed and used for association and linkage studies. Differential display analysis of skeletal muscle transcripts were used to identify new candidate genes for the response to endurance exercise. Finally, a genome wide search was undertaken to isolate candidate genomic regions and positional candidate genes for the response of cardiorespiratory endurance and cardiovascular and NIDDM risk factor phenotypes. The study was renewed in 2001 for four years to continue analyses of the data.

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