Influence of the ACTN3 R577X genotype on the injury epidemiology of marathon runners

Abstract

A common single nucleotide polymorphism in the ACTN3 gene might result in the complete deficiency of α-actinin-3 (i.e., XX genotype). It has been found that ACTN3 XX individuals have several traits related to lessened muscle performance. This study aimed to determine the influence, if any, of ACTN3 genotypes on injury incidence of marathoners during the year preceding to participating in a competitive marathon race. Using a cross-sectional experimental design, the type and conditions of sports injuries were documented for one year in a group of 139 marathoners. Injuries were recorded following a consensus statement on injuries in Athletics. Afterward, ACTN3 genotyping was performed, and injury epidemiology was compared among RR, RX, and XX genotypes. The distribution of the RR/RX/XX genotypes was 28.8/42.8/23.5%, respectively. A total of 67 injuries were recorded. The frequency of marathoners that reported any injury during the previous year was not different across the genotypes (55.0/38.8/40.6%, P = 0.241). Although the overall injury incidence was not different among genotypes (2.78/1.65/1.94 injuries/1000 h of running, P = 0.084), the likelihood of suffering an injury was higher in RR than in RX (OR = 1.93: 95%CI = 0.87-4.30), and higher than in XX (OR = 1.79: 0.70-4.58). There was no difference in the conditions, severity, body location, time of year, or leading cause of injury among genotypes. However, XX presented a higher frequency of sudden-onset injuries (P = 0.024), and the OR for muscle-type injuries was 2.0 (0.51-7.79) times higher compared to RR runners. Although XX marathoners did not have a higher overall incidence of injury, the OR in these runners for muscle-type injuries was superior to RR and RX runners. The likelihood of suffering a muscle injury, especially with a sudden-onset, was twice in XX than in RR endurance runners.

Effect of ACTN3 Genotype on Sports Performance, Exercise-Induced Muscle Damage, and Injury Epidemiology

“…On the contrary, a study with first-division soccer players displayed that those players with the XX genotype had a threefold higher likelihood of suffering muscle injuries [ 59 ]. Since these two initial investigations with distinct outcomes, the evidence pointing to XX athletes being more prone to suffering sports-related muscle injuries when compared to RR counterparts has evolved, confirming, in most cases, the negative role of the ACTN3 XX genotype on non-contact muscle injuries in cohorts of elite performance players [ 60 ] and amateur marathon runners [ 15 ]. In these investigations, besides the injury incidence, XX athletes had a higher frequency of sudden-onset injuries [ 15 ] and the injuries reported needed more days for full recovery [ 59 ].…”

“…Since these two initial investigations with distinct outcomes, the evidence pointing to XX athletes being more prone to suffering sports-related muscle injuries when compared to RR counterparts has evolved, confirming, in most cases, the negative role of the ACTN3 XX genotype on non-contact muscle injuries in cohorts of elite performance players [ 60 ] and amateur marathon runners [ 15 ]. In these investigations, besides the injury incidence, XX athletes had a higher frequency of sudden-onset injuries [ 15 ] and the injuries reported needed more days for full recovery [ 59 ]. Although the mechanism to explain the likely higher incidence of sports-related muscle injury in XX athletes is yet to be found, it may be speculated that the lack of α-actinin-3 reduces the capacity of the skeletal muscle to endure the exercise contractions that lead to muscle injury.…”

“…Moreover, it has been proposed that the ACTN3 genotype controls the sarcomeric composition and muscle function in a dose-dependent fashion, indicating that RR individuals are the ones with a higher amount of α-actinine-3 within the muscle, even when compared to RX individuals [ 14 ]. Although α-actinin-3 deficiency is compensated for by a higher expression of α-actinin-2, the fast type II fibers, scientific evidence has shown that the ACTN3 XX genotype is underrepresented in elite power-oriented athletes [ 9 ], while it may be related to several phenotypes associated to a higher predisposition to sport-related injury [ 15 ]. Thus, the ACTN3 XX and the subsequent deficiency of α-actinin-3 may be indicative of a negative effect of this genetic variation on the function of fast-twitch muscle fibers.…”

Effect of ACTN3 R577X Genotype on Injury Epidemiology in Elite Endurance Runners

“…Recent investigations have found that XX athletes might also be more prone to suffer sports-related muscle injuries when compared to RR counterparts [ 12 , 13 , 14 ], although this is not always the case [ 15 ]. There is greater consensus on the higher predisposition of XX individuals to ankle sprains [ 16 , 17 , 18 ] and high levels of muscle damage during endurance competitions [ 19 , 20 ].…”

“…All this information suggests an a priori predisposition of XX athletes to sports-related injuries, but a lack of replication is present for most current findings that associate genetics with a predisposition to sports injury, as recently suggested [ 21 ]. For this reason, we aimed to determine the influence of the ACTN3 R577X polymorphism on the injury epidemiology of elite endurance athletes, following the methodology of a previous investigation carried out on amateur endurance runners [ 12 ]. We obtained information to characterize the influence of this polymorphism on injury epidemiology, such as incidence, conditions, severity, mode of onset, body location, and cause that led to each injury in elite runners with different ACTN3 genotypes.…”