Angiotensin-converting enzyme genotype affects the response of human skeletal muscle to functional overload

The response to strength training varies widely between individuals and is considerably influenced by genetic variables, which until now, have remaine d unidentified. The deletion (D), rather than the insertion (I), variant of the human angiotensin-converting enzyme (ACE) genotype is an important fac tor in the hypertrophic response of cardiac muscle to exercise and could al so be involved in skeletal muscle hypertrophy - an important factor in the response to functional overload. Subjects were 33 healthy male volunteers w ith no experience of strength training. We examined the effect of ACE genot ype upon changes in strength of quadriceps muscles in response to 9 weeks o f specific strength training (isometric or dynamic). There was a significan t interaction between ACE genotype and isometric training with greater stre ngth 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 consisten t genotype and training interaction (ID > DD > II) was observed across all of the strength measures, and both types of training. ACE genotype is the f irst genetic factor to be identified in the response of skeletal muscle to strength training. The association of the ACE I/D polymorphism with the res ponses of cardiac and skeletal muscle to functional overload indicates that they may share a common mechanism. These findings suggest a novel mechanis m, involving the renin-angiotensin system, in the response of skeletal musc le to functional overload and may have implications for the management of c onditions such as muscle wasting disorders, prolonged bed rest, ageing and rehabilitation, where muscle weakness may limit function.