Human angiotensin‐converting enzyme I/D and α‐actinin 3 R577X genotypes and muscle functional and contractile properties

Abstract

The angiotensin-converting enzyme (ACE) I/D and α-actinin 3 (ACTN3) R/X polymorphisms have been suggested to influence variations in skeletal muscle function. This study investigated the association between ACE I/D and ACTN3 R/X polymorphisms and muscle strength and contractile properties in young UK Caucasian men. Measurements of the knee extensor muscles were taken from 79 recreationally active but non-strength-trained males on two occasions. Isometric knee extensor strength was measured using a conventional strength-testing chair. Maximal twitches were electrically evoked by percutaneous stimulation to assess time-topeak tension, half-relaxation time and peak rate of force development. The torque-velocity relationship was measured at four angular velocities (0, 30, 90 and 240 deg s −1 ) using isokinetic dynamometry, and the relative torque at high velocity was calculated (torque at 240 deg sas a percentage of that at 30 deg s −1 ). The ACE I/D and ACTN3 R/X polymorphisms were genotyped from whole blood by polymerase chain reaction. Serum ACE activity was assayed from serum using automated spectrophotometry. Physical characteristics were independent of either genotype. Absolute and relative high-velocity torque were not influenced by ACE or ACTN3 genotypes. Isometric strength and the time course of a maximal twitch were independent of ACE and ACTN3 genotypes. Serum ACE activity was significantly dependent on ACE genotype (P < 0.001), but was not associated with any measure of functional or contractile properties. Knee extensor functional and contractile properties, including high-velocity strength, were not influenced by ACE and ACTN3 polymorphisms in a cohort of UK Caucasian males. Any influence of these individual polymorphisms on human skeletal muscle does not appear to be of sufficient magnitude to influence function in free-living UK Caucasian men. Genetic factors are thought to determine 20-80% of the variation in a number of traits important to athletic performance (MacArthur & North, 2007), for example the relative proportion of fast-and slowtwitch skeletal muscle fibres (Simoneau & Bouchard, 1995; ∼45% due to inherited factors). The annual publication of the human gene map for performance and health-related fitness phenotypes (Rankinen et al. 2006) lists more than 150 genes or genetic regions associated with athletic performance and physical fitness traits. The angiotensin-converting enzyme (ACE) I/D polymorphism (Williams et al. 2005) and α-actinin 3 (ACTN3) R577X polymorphism (Mills et al. 2001) have recently been identified as potential influences contributing to variations in skeletal muscle composition, function and performance.The ACE gene has been the most extensively studied gene in the area of human performance phenotypes. A functional polymorphism of the ACE gene is defined as the presence (insertion, I allele) or absence (deletion, D allele) of a 287-amino-acid base pair Alu repeat sequence within intron 16 of the ACE gene on chromosome 17 (Rigat et al. 1990). The polymorphism results in th...

Does the ACE I/D polymorphism, alone or in combination with the ACTN3 R577X polymorphism, influence muscle power phenotypes in young, non-athletic adults?

“…Thus, with the present design for phenotype assessment, the hypothesis that ACE I/D and ACTN3 R557X genotypes might exert a combined influence on leg muscle phenotypes was not corroborated. Though controversy exists (McCauley et al 2009(McCauley et al , 2010Moran et al 2006), the ACE D allele has been associated with power-related phenotypes in non-athletic populations (Giaccaglia et al 2008;Hopkinson et al 2004;Yamin et al 2007); this allele has also been associated with elite "sprint" athletic performance (Myerson et al 1999;Woods et al 2001), though more recent data do not corroborate such association Scott et al 2005Scott et al , 2010. However, the association between leg 'explosive' muscle power and the ACE I/D polymorphism had not been studied to date.…”

“…ACE) or circulating levels of the muscle growth factor angiotensin II. With regard to this, although serum ACE activity was suggested to be significantly dependent on ACE genotypes in young Caucasian adults (with the highest enzymatic levels been found in the DD genotype), it does not seem to influence their muscle functional or contractile properties (McCauley et al 2009). Further research is also necessary to assess the combined influence of other candidate genes with a potential effect on muscle phenotypes, e.g.…”

“…isokinetic tests involving single-joint movements (e.g. knee-extension) at relatively low angular velocities (<240° s _1 ) (McCauley et al 2009(McCauley et al , 2010. Indeed, during actual, natural high muscle power actions (e.g.…”

“…sprinting and jumping events), especially in women (Yang et al 2003). More discrepancy exists on the putative role of the ACTN3 R577X polymorphism on muscle power phenotypes in non-athletic populations, with some authors reporting an unfavourable effect of the XX genotype (Vincent et al 2007), at least in women (Walsh et al 2008), and others reporting no effect (McCauley et al 2009). Additional controversy stems from the fact that in older adults (mean age ~ 65 years), the XX genotype was associated with higher knee extensor concentric peak power compared with RR and RX genotypes (Delmonico et al 2007), while others found no genotype:phenotype association (San Juan et al 2006).…”

ACE I/D and ACTN3 R/X polymorphisms as potential factors in modulating exercise-related phenotypes in older women in response to a muscle power training stimuli

“…It seems that the DD genotype may be associated with a greater proportion of fast-twitch fibers (Zhang et al 2003) which could explain the possible influence of the ACE D-allele upon strength/ power, particularly at high velocity tasks (Costa et al 2009). However this evidence remains equivocal (Folland et al 2000;Woods et al 2001;Pescatello et al 2006;McCauley et al 2009;. Moreover, to our knowledge, no studies have examined the influence of ACE DD genotype on high-speed power traininginduced changes in older Caucasian women.…”