Angiotensin‐Converting Enzyme Genotype Affects the Response of Human Skeletal Muscle to Functional Overload

Abstract

The response to strength training varies widely between individuals and is considerably influenced by genetic variables, which until now, have remained unidentified. The deletion (D), rather than the insertion (I), variant of the human angiotensin‐converting enzyme (ACE) genotype is an important factor in the hypertrophic response of cardiac muscle to exercise and could also be involved in skeletal muscle hypertrophy – an important factor in the response to functional overload. Subjects were 33 healthy male volunteers with no experience of strength training. We examined the effect of ACE genotype upon changes in strength of quadriceps muscles in response to 9 weeks of specific strength training (isometric or dynamic). There was a significant interaction between ACE genotype and isometric training with greater strength gains shown by subjects with the D allele (mean ± S.E.M.: II, 9.0 ± 1.7%; ID, 17.6 ± 2.2%; DD, 14.9 ± 1.3%, ANOVA, P 0.05). A consistent genotype and training interaction (ID DD II) was observed across all of the strength measures, and both types of training. ACE genotype is the first genetic factor to be identified in the response of skeletal muscle to strength training. The association of the ACE I/D polymorphism with the responses of cardiac and skeletal muscle to functional overload indicates that they may share a common mechanism. These findings suggest a novel mechanism, involving the renin‐angiotensin system, in the response of skeletal muscle to functional overload and may have implications for the management of conditions such as muscle wasting disorders, prolonged bed rest, ageing and rehabilitation, where muscle weakness may limit function.

Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men

“…In keeping with this hypothesis, modulation by genetic variants of the skeletal response induced by strenuous exercise has previously been reported 16,17 . By expressing exon 18 alleles in the context of their haplotype in vitro, we found the T variant to be associated with a significantly decreased response to canonical Wnt3a signaling.…”

“…Nevertheless, there is some evidence that genetic variation may influence the response of muscles and the skeleton to intense physical training. 16,17 Recently, mutations in the lipoprotein receptor-related protein 5 (LRP5) gene have been demonstrated to result in different single gene disorders with either a high or low BMD phenotype 18 . Thus in the autosomal recessive disorder, osteoporosis-pseudoglioma syndrome (OPPG), very low bone mass and blindness have been linked to loss-of-function mutations in the LRP5 gene.…”

Association of Genetic Factors With Selected Measures of Physical Performance

“…The subjects with the ID and DD genotypes improved their quadriceps muscle strength 97% and 66% more than did the subjects with the II genotype, respectively. 11 Folland and colleagues 11 speculated that the ACE genotype that regulates hypertrophic responses in other tissues has a similar effect in skeletal muscle. The D allele has been associated with higher systemic 28 and cardiac tissue 29 ACE activities.…”

“…31,32 The interaction of ACE in the same fashion in skeletal muscle may represent a possible mechanism for the greater strength gains associated with the D allele. 11 However, hypertrophy may not be the only measure of strength gain, as there have been reports of inconsistencies in the relationship between muscle size and strength. 33 Studies also have shown a greater frequency of the D allele among athletes who compete in shorter-distance events.…”

“…26 Furthermore, Reneland and Lithell 27 found considerable ACE activity in skeletal muscle. These studies prompted Folland and colleagues 11 to investigate the influence of the D allele on the response of human quadriceps muscles to specific strength training programs in young men who were healthy; they hypothesized that if the D allele were associated with skeletal muscle hypertrophy, then subjects with the D allele would respond with a greater strength increase than would those without this allele. The subjects of the study participated 3 times per week for 9 weeks in strength training protocols that involved isometric knee extension training with 1 leg and dynamic knee extension training with the other leg.…”