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An inherited form of AMPD deficiency has been attributed to a non-sense mutation (C to T transition in nucleotide 34) in exon 2 of AMPD1 gene. AMPD deficiency causes AMP accumulation, which can lead to the production of adenosine by AMP 5'-nucleotidase. It is known that adenosine accumulation exerts a vasodilatory response, which could have physiological consequences during exercise. PURPOSE To examine associations of the C34T polymorphism of the AMPD1 gene with cardiorespiratory and performance phenotypes during cycling exercise at absolute and relative power outputs progressing to exhaustion before and after endurance training for 20 weeks in the HERITAGE Family Study cohort (n = 779). Since no Blacks were mutant homozygotes (TT), only Caucasians were considered for analysis (400 normal homozygotes, CC; 97 heterozygotes, CT; and 6 TT). RESULTS Sedentary State. Cycling at the absolute workload of 50 W resulted in higher rate of perceived exertion in TT (p < 0.0001). At the relative intensity of 60% of VO2 max, stroke volume was lower in TT (p < 0.05). Maximal values for power output, SBP, HR, VCO2, and RER were lower in TT (p < 0.05). Response to Training. The cardiorespiratory training response at 50 W and at 60% of VO2 max was similar across C34T-AMPD1 genotypes. However, max ventilation, max VO2, and max VCO2 during exercise increased less in TT (p < 0.01). CONCLUSION The results indicate that subjects with the TT genotype at the C34T AMPD1 gene have diminished exercise capacity and cardiovascular and ventilatory responses to exercise. Endurance training improves submaximal exercise cardiorespiratory and performance phenotypes in carriers of the C34T mutation as much as in non-carriers, but the training response of ventilatory phenotypes during maximal exercise is more limited in TT. Supported by multiple grants from NIH
Excess body fat or body mass relative to height aggregates in families. It is commonly recognized that this familial aggregation of human obesity is accounted for in part by a significant genetic component. Thus the genetic heritability of the obesity phenotypes accounts for ∼25–40% of the age- and gender-adjusted phenotypic variances. There is also growing evidence that single-gene effects can be detected under appropriate conditions. The focus of research has now shifted to candidate genes and DNA markers of various obesity phenotypes. To date, linkage results have been published from the Pima Indian Study, the San Antonio Family Heart or Diabetes Studies, the Paris Cohort of Obese Siblings, the University of Pennsylvania Family Obesity Study and the Quebec Family Study. The only genomic scan (with ∼600 markers) reported to date is that from the Pima Indian sibling study. In that study, the strongest evidence for linkage with body fat was with markers on chromosome 11q, 6p and 3p. Evidence for linkage with markers on 7q was obtained in all family studies with the only apparent exception being the Pima Indians. Our own results from the Quebec Family Study suggest that there are linkages between body fat, as assessed from hydrodensitometry, and markers on 1p32–p22. Other linkages have been reported in the past but they are generally based on smaller sample size and weaker evidence.
The extent of the growth changes in maximal work output during 10 s (MWO10), 30 s (MWO30), and 90 s (MWO90) of maximal repetitive knee flexions and extensions assessed on a modified Hydra-Gym machine was investigated in 84 boys and 83 girls, 9–19 yr of age. Body weight, fat mass and fat free mass by underwater weighing, and thigh volume and cross-sectional area were also determined. No difference was observed in the absolute MWO10, MWO30, and MWO90 between girls and boys at 9 and 11 yr of age. However, significant differences appeared between genders from 13 yr of age onward, anaerobic performances of the knee extensor muscles of girls representing about 75% or even less of those of boys. The analysis of variance revealed that maximal work output during the three knee extension tests was significantly greater in males as well as in females from 9 to 18 yr, regardless how performance was related to morphological characteristics. Performance in absolute values or expressed per unit of body weight, fat free mass, and thigh cross-sectional area for the MWO10, MWO30, and MWO90 tests were almost always significantly lower in both genders when performances of the 9-yr-old group were compared with those of the 13-yr-old group or older groups. Improvement in maximal work output during the 10-s, 30-s, or 90-s knee extension tests with age occurred mainly between 9 and 15 yr in both genders. The results of the present study show that there are gender differences in predominantly anaerobic performances during growth and reveal that increase in muscle mass does not appear to be the only factor responsible for the age- related increment in the anaerobic working capacity of the knee extensor muscles.
No abstract is provided for this article.
Regular exercise and a physically active lifestyle have favorable effects on health. Several issues related to this theme are addressed in this report. A comment on the requirements of personalized exercise medicine and in-depth biological profiling along with the opportunities that they offer is presented. This is followed by a brief overview of the evidence for the contributions of genetic differences to the ability to benefit from regular exercise. Subsequently, studies showing that mutations in TP53 influence exercise capacity in mice and humans are succinctly described. The evidence for effects of exercise on endothelial function in health and disease also is covered. Finally, changes in cardiac and skeletal muscle in response to exercise and their implications for patients with cardiac disease are summarized. Innovative research strategies are needed to define the molecular mechanisms involved in adaptation to exercise and to translate them into useful clinical and public health applications.
This chapter deals with the genetics of body fat content, regional fat distribution, and nutrient partitioning phenotypes. The comparison of monozygotic (MZ) twins reared apart with MZ twins reared together represents an interesting design to assess the role of heredity with some control over some of the confounding influences of shared environment. During the last 60 years or so, a large number of authors have reported that obese parents have a higher risk of having obese children than lean parents. Nutrient partitioning can be defined in terms of the pattern of deposition of the ingested energy in the form of fat (lipid) or lean (protein) tissue. Cells and tissues of the body are exposed to the same profile of blood substrates and humoral factors. Upper body obesity is more prevalent in males than in females, and it increases in frequency with age in males and after menopause in females.
