A fundamental response to endurance exercise training is an increase in V̇o2max. However, when large groups of young and middle-aged subjects are exposed to similar training programs, the increase in V̇o2max can be quite variable. In some subjects, V̇o2max might increase only 5–10%, whereas in others, training at the same frequency and intensity duration might lead to a 30–40% increase in V̇o2max. Studies conducted in twins and siblings over many years suggest much of this variability in response to training (i.e., trainability) is genetically determined. A number of investigators using a number of approaches are attempting to unravel the “genetics” of trainability using several approaches. In this “News Briefs” section, we highlight three recent papers that address the possibility that differences in the genes that code for the angiotensin-converting enzyme (ACE) might explain differences in trainability.
Angiotensin is a powerful vasoconstricting hormone that acts at various sites in the cardiovascular system. Each individual contains two genes for ACE. There is an I (insertion) form of the ACE gene and a D (deletion) form of the gene. Individuals with the II genotype have lower ACE activities, and individuals with the DD genotype have much higher levels. Individuals who have ID typically have intermediate levels. Approximately 25% of individuals are II, 50% are ID, and 25% are DD. Because this enzyme plays a key role in generating angiotensin from its precursors, there has been great interest in its role in various pathological and physiological adaptations in the cardiovascular system. In addition, some of the drugs most commonly used to treat cardiovascular disease (ACE inhibitors) target this enzyme. There has been some evidence regarding, and much discussion about, ACE genotype and V̇o2max.
Hagberg, J.M., R.E. Ferrell, S.D. McCole, K.R. Wilund, and G.E. Moore. V̇o2max is associated with ACE genotype in postmenopausal women.J. Appl. Physiol.85:1842–1846, 1998. In this paper, Hagberg and colleagues sought to determine whether the ACE genotype of a group of postmenopausal women predicted V̇o2max in a cross-sectional study. The authors evaluated the impact of the ACE II versus ID versus DD genotype on V̇o2max and cardiac output in postmenopausal women with different habitual physical activity levels. Within each genotype, age, body composition, and habitual physical activity level were similar. ACE II genotype carriers had V̇o2max values that were 15–20% higher (6.3 mL·kg-1·min-1) than those of women with the ACE DD genotype. Values for individuals with the ACE ID genotype were intermediate between the groups. The difference in V̇o2max among ACE genotype groups was the result of differences in maximal a-vO2 difference and ACE genotype accounted for ˜ 17% of the variation in maximal a-vO2 difference. Maximal cardiac output index did not differ. The authors conclude that the ACE genotype accounts for a significant portion of the individual differences in V̇o2max among postmenopausal women and that the difference was the result of differences in maximal a-vO2 difference.
Rankinen, T., B. Wolfarth, J.A. Simoneau, D. Maier-Lenz, R. Rauramaa, M.A. Rivera, M.R. Boulay, Y.C. Chagnon, L. Perusse, J. Keul, and C. Bouchard. No association between the angiotensin-converting enzyme ID polymorphism and elite endurance athlete status.J. Appl. Physiol.88:1571–1575, 2000. In contrast to the cross-sectional study by Hagberg and colleagues, Rankinen and colleagues conducted two studies on the impact of ACE polymorphisms on V̇o2max. In this study on elite athletes, they evaluated the frequency of ACE polymorphism in 192 male endurance athletes with a maximal oxygen uptake of >75 mL·kg-1 and in 189 sedentary male controls. Their main conclusion was that there was no “excess” of the type I allele among the athletes in comparison with controls. They also looked at the athletes who had the highest V̇o2max values (≥83 mL·kg-1·min-1) and found no evidence for increased frequency of the I allele. The authors then discuss in detail the limitations of their study and other studies on this topic.
Rankinen, T., L. Perusse, J. Gagnon, Y.C. Chagnon, A.S. Leon, J.S. Skinner, J.H. Wilmore, D.C. Rao, and C. Bouchard. Angiotensin-converting enzyme ID polymorphism and fitness phenotype in the HERITAGE family study.J. Appl. Physiol.88:1029–1035, 2000. In this training study, 724 previously sedentary humans were exposed to a standardized endurance exercise training program for 20 wk. A large number of families from several racial groups participated. These authors found that white “offspring” with the ACE DD genotype had the largest increases in V̇o2max in response to the training. Baseline V̇o2max averaged 2.6–2.7 L·min-1 in the three genotypes. The ACE II and ID genotypes showed an average increase in V̇o2max of ˜ 400–420 mL·min. Those with the DD genotype showed an increase of ˜ 480 mL·min. Again, the role of the ACE genotype and the response training is thoroughly discussed.
Genes coding for ACE have received much attention recently as possible “genetic markers” of V̇o2max and “trainability.” Despite all of the discussion, it is unclear whether these genes might contribute to high V̇o2max values or increased trainability via a direct physiologic mechanism or whether they are merely associated with some other genes that might be key determinants of V̇o2max and/or trainability. Although initial studies seemed to suggest that individuals with the ACE II or ID genotype might have higher V̇o2max values and be more “trainable,” more recent studies have cast serious doubt on this proposition. The three papers cited here offer excellent discussions of problems associated with trying to understand the genetic determinants of human with performance. All highlight the basic proposition that issues related to experimental design and subject selection will be absolutely essential in designing valid experiments that address issues related to genes and human performance. This general topic is likely to receive even more attention with the completion of the human genome project and the resultant increase in “candidate” genes that might be associated with athletic performance of the response to training.