Genes Associated with Muscle, Tendon and Ligament Injury Epidemiology in Women’s Amateur Football Players
1
Exercise and Sport Science, Faculty of Health Sciences, Universidad Francisco de Vitoria, 28223 Pozuelo, Spain
2
SPORTNOMICS S.L., 28922 Madrid, Spain
Appl. Sci. 2024, 14(5), 1980; https://doi.org/10.3390/app14051980
Submission received: 1 February 2024
/
Revised: 21 February 2024
/
Accepted: 26 February 2024
/
Published: 28 February 2024
(This article belongs to the Special Issue Sports Medicine: Latest Advances and Prospects)
Abstract
:Background: There is a lack of specific genetic studies regarding injuries in women’s football. However, different genetic factors have been associated with tendon/ligament injuries in women football players. The aim of the study was to examine the genotypic frequencies of genes associated with injury risk and epidemiology in women’s amateur football players and the aetiology of injuries. Methods: In total, 168 women’s amateur football players from football clubs in the Spanish second division league and Caucasian descent were enrolled in this prospective observational cross-sectional study. AMPD1 (rs17602729), ACE (rs4646994), ACTN3 (rs1815739), CKM (rs8111989) and MLCK (rs2849757 and rs2700352) polymorphisms were genotyped. The characteristics of 169 non-contact injuries during the 2022/2023 season were classified following the International Olympic Committee (IOC) Consensus Statement for reporting injuries as follows: musculoskeletal, tendon/ligament, injury setting; and severity. The disequilibria of polymorphisms were estimated using the Hardy–Weinberg Equilibrium (HWE). The characteristics of the injuries were recorded, and the genotype characteristics were analysed. The genotype frequencies of all polymorphisms were compared between non-injured and injured football players and injury aetiologies. Results: The AMPD1 genotype distribution differed between tendon/ligament injured and non-injured (p = 0.003) with a higher frequency in the TT genotype and T allele. The genotype distribution was different for the CKM and MLCK c.37885C>A polymorphisms in training and match injuries (p = 0.038 and p = 0.031, respectively). In the ACTN3 and AMPD1 polymorphisms, the distribution of the TT genotype in both genes showed a higher frequency in severe injuries (all p < 0.001). Conclusions: Tendon/ligament injury epidemiology in women’s amateur football players was associated especially with the TT genotype of the AMPD1 gene. The TT genotype of the AMPD1 and ACTN3 genes was also associated with severity, and the CKM and MLCK polymorphisms were associated with injury settings.
1. Introduction
Football is the most played sport in the world by children and adults with varying degrees of experience and skill [1]. Women players must repeatedly perform sudden accelerations and decelerations, rapid changes in direction, jumps and landings [2,3]. These high-intensity situations, together with frequent exposure to collisions and contact, leads to a marked increase in the risk of injury in this sport compared to individual sports [4,5], and football is one of the five sports in which players are most at risk of injury [2].
Women football players have unique morphological and body composition characteristics [6] with a smaller body size and lower body mass than men football players. However, they have a higher percentage of body fat, which contributes to a higher epidemiology of fracture injuries [7,8].
The risk of serious knee injuries (such as anterior cruciate ligament (ACL) rupture) is at least twice as high in women as in men, regardless of exposure or level of participation [9]; they also have a higher risk of concussions and [10,11] knee [12] and ankle injuries [13]. Training intensity, biomechanics and hormonal differences may also contribute to this epidemiology of injuries in women football players [14,15]. The injury rate among professional and amateur players may vary, showing in amateur players an incidence of 9.6/1000 h of exposure and in professional football players, that of 8.1/1000 h of exposure [16]. Exercise-based prevention programmes may reduce the risk of non-contact musculoskeletal injuries by 23% among football players [16,17].
In recent years, genetics, especially in single nucleotide polymorphism (SNP) studies, has provoked great interest in susceptibility to injury and in the characteristics of tissues that are more prone to injury, because these play such important roles [18,19,20]. Genetics play an important role in determining the structure and function of connective tissue such as muscles, tendons and ligaments. Several genetic polymorphisms can influence the elasticity, strength and resilience of these tissues, which in turn can increase susceptibility to injury [21]. Some of the genes associated with the increased risk of muscle, tendon and ligament injuries include those related to the composition of collagen and elastin, which are key structural proteins in these tissues, and genetic variants that affect the production or quality of collagen may increase vulnerability to tendon and ligament injuries, specially the COL5A1 gene [22]. There are some important reasons to consider, like genetic variability, tissue structure and composition, tissue functional properties, inflammatory responses and tissue repair and hereditary risk factors [21,23].
Several studies have shown the association of genetics, especially in muscle injuries, focusing on the alpha-actinin 3 (ACTN3) and angiotensin-converting enzyme isoform 1 (ACE1) genes [20,24,25,26]. However, recent studies focusing on genetic scores in genes related to sport injuries have shown that the gene associated with muscle metabolism, adenosine monophosphate deaminase 1 (AMPD1), is mostly responsible for muscle injuries in men’s professional football players [18] and men and women elite endurance athletes [27], discovering new associations in muscle injuries in football players in the creatine kinase muscle (CKM) gene [19], and the myosin light chain kinase (MLCK) gene (also known as MYLK) and muscle damage during sports practice in men and women endurance runners [28]. To date, there has been a lack of specific genetic studies regarding injuries in women’s football compared to other sports or even in men’s football. However, different genetic factors have been associated with knee injuries in women football players [29].
Therefore, the aim of the research was to study the genotypic frequencies of genes associated with injury risk and epidemiology in musculoskeletal and tendon/ligament injuries and the aetiology of injuries occurring in women’s amateur football players. The hypothesis was based on previous studies that genetics is associated with the epidemiology of injury in women football players and could have a significant effect on musculoskeletal and tendon/ligament injuries, especially in AMPD1 and ACTN3 polymorphisms.
2. Materials and Methods
2.1. Participants
This epidemiological cross-sectional descriptive study analysed 168 Spanish women’s amateur football players in the Spanish second division league during the 2022/2023 season. All of the women’s amateur football players were of Spanish Caucasian descent (Caucasian descent for the population of ≥3 generations). The characteristics of this cohort are presented in Table 1.
The following inclusion criteria were established: (a) women´s amateur football players >18 years; (b) women’s amateur football players with a contract with the first team of the football club; (c) players who had participated in training and matches throughout the season at the same football club; and (d) players who had performed regular exercise training of >1 h per session, ≥3 days per week during the previous 6 months. Exclusion criteria were (a) players with only contact injuries during the season; (b) disabling injuries for football training or matches in the 6 months prior to the start of the study; and (c) women’s professional football players.
Written informed consent was obtained from all subjects. The protocol of the study was approved by the Ethics Committee of the University Francisco de Vitoria (UFV 32/2020) and conducted in accordance with the Declaration of Helsinki for Human Research of 1964 (last modified in 2013). All of the women football players in the study were included with codification identifiers.
2.2. Deoxyribonucleic Acid (DNA) Sample and Genotyping
Samples were collected with SARSTED swabs by buccal smear and kept refrigerated until genotyping.
DNA extraction from the swabs was carried out through automatic extraction using QIACube equipment (QIAGEN, Venlo, The Netherlands), yielding a DNA concentration of 25–40 ng/mL, which was kept in a solution in a volume of 100 μL at −20 °C until genotyping.
ACE I/D (rs4646994), ACTN3 c.1729C>T (rs1815739), AMPD1 c.34C>T (rs17602729), CKM c.*800A>G (rs8111989) and MLCK c.49C>T (rs2700352) and c.37885C>A (rs28497577) polymorphisms were genotyped using Single Nucleotide Primer Extension (SNPE) with a SNaPshot Multiplex Kit (Thermo Fisher Scientific, Waltham, MA, USA), with an analysis of the reaction result conducted using capillary electrophoresis fragments, in an ABI3500 unit (Applied Biosystems, Foster City, CA, USA) with a bioinformatic analysis performed using GeneMapper 5.0 software (Applied Biosystems, Foster City, CA, USA).
2.3. Injury Recording
This research prospectively included the records of all the players during the 2022/2023 season with injuries, and their characteristics. For each injury, the medical staff provided the date of injury, onset (acute or repetitive/overuse), injury setting (training or match), player position (goalkeeper or field player), injury location, type of injury (the specific injury diagnosis was also recorded), injury severity based on layoff time (0 days (when a player could not participate fully on the day of an injury but was available for full participation the next day), slight (1–3 days), mild (4–7 days), moderate (8–28 days), or severe (>28 days)) [30] of all non-contact injuries reported by the clubs’ medical services. To be included in the analysis, the injury had to have been a consequence of exposure to football during training or competition. Injuries caused by a collision with another player or an object were excluded from the investigation as they are potentially not affected by the player’s genotype. The injury collection followed the international consensus statement on procedures for the epidemiological studies of injuries in football recommended by the Fédération Internationale de Football Association (FIFA) and the Union of European Football Associations (UEFA) [31,32]. The definition of the International Olympic Committee (IOC) consensus statement was used to classify injury severity reporting data on the day of the injury and the day of returning to play.
2.4. Statistical Analysis
The statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS), v.21.0 for Windows. (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. IBM Corp.: Armonk, NY, USA). The normality of each variable was initially tested using the Kolmogorov–Smirnov test. Descriptive statistics were calculated for each genotype. The genotype frequencies of all polymorphisms were compared between non-injured and injured football players and injury aetiologies, using a χ2 test. The disequilibria of SNPs were estimated using the Hardy–Weinberg Equilibrium (HWE). The characteristics of the injuries were recorded, and the genotype characteristics were analysed using the χ2 test. To determine what genotype was associated with an unexpected distribution, the standardised residuals were calculated based on the difference between the observed and the expected values. Briefly, within each injury variable, a genotype was considered to have a statistically different distribution from the expected value when its distribution was > or < the critical Z-score value (i.e., 1.96).
The significance level was set at p < 0.050.
3. Results
All the polymorphisms analysed met the HWE (all p > 0.05). The genotype frequencies for the six polymorphisms in the women’s amateur football players are shown in Table 2.
In total, 93 (55.4%) women’s amateur football players suffered a non-contact injury during the season, for a total of 169. The remaining 75 players (44.6%) had no injuries during the season. The characteristics of the injuries recorded and analysed during the season are presented in Table 3.
The genotypic distribution in the epidemiology of injured women’s amateur football players compared to the non-injured players showed no statistical differences in any polymorphism (all p > 0.050) (Table 4).
3.1. Musculoskeletal Injuries
3.2. Tendon/Ligament Injuries
In total, 43 (25.5%) women’s amateur football players suffered a total of 92 (54.3%) tendon/ligament injuries.
The AMPD1 genotype distribution differed between tendon/ligament injured and non-injured players (p = 0.003) with a significant higher frequency of the TT genotype in injured versus non-injured players (33.7% vs. 14.3%, respectively) and a lower frequency of the CC in injured versus non-injured players (4.3% vs. 53.2%) (Table 4).
3.3. Injury Settings
Of the 169 non-contact injuries analysed, 99 (58.6%) occurred in matches, while 70 (41.4%) occurred during training.
The genotype distribution was different for the CKM c.*800A>G polymorphism (p = 0.038), showing that the GG genotype had a higher frequency in training injuries compared to those observed in matches (29.2% vs. 6.1%, respectively) (Table 5). The MLCK c.37885C>A polymorphism showed a higher frequency of the CA genotype in players injured in matches than those injured during training (32.4% vs. 8.3%) (p = 0.031) (Table 5).
3.4. Severity
In total, 29 (17.1%) injuries were severe, while 140 (82.9%) were non-severe.
In the ACTN3 c.1729C>T polymorphism, the genotype distribution differed between severely injured and non-severely injured players (p < 0.001), showing in the TT genotype a higher frequency in players with severe injuries than those with non-severe injuries (51.8% vs. 3.6%) (Table 5). Regarding the AMPD1 c.34C>T polymorphism, differences in genotype distribution were observed in the TT genotype, with a higher frequency in players with severe injuries than those with non-severe injuries (75.9% vs. 20.7%) (p < 0.001) (Table 5).
4. Discussion
Although the physiology and aetiology of injuries in the world of women’s football have been studied extensively, genetics remains a field that deserves more interest, and the author is presenting, for the first time, a study on the association between muscle injury-related genes and the epidemiology of injuries in women’s amateur football players during a whole season. The aim of this study was to examine the association between muscle injury-related genes, injury risk and injury aetiology in women’s amateur football players. The main finding is the correlation between genotype frequencies and different injury characteristics, with the C allele of the AMPD1 c.34C>T polymorphism, suggesting some kind of benefit related to injury prevention, especially for protection against tendon/ligament injuries and severity, as well as with the C allele of the ACTN3 c.1729C>T polymorphism.
The morphological characteristics of women football players may increase the risk of injuries such as stress fractures, and affect their overall strength and power on the pitch, as well as expose them to higher risks to certain types of injuries, as shown in previous studies on the Spanish League [15,33].
In recent years, the demands of training and matches have increased considerably in women’s football, even for amateurs [34]. The overall epidemiology of injuries is similar to that of men’s football, although the proportion of severe injuries is higher in women football players [2,35], totalling 17.2% in this study, showing a higher frequency of injuries than previously reported in men football players [36], which could be associated with significant costs [37]. The risk of severe knee injuries and ankle sprains is at least twice as high in women as in men football players, regardless of exposure or level of participation [38,39], which is consistent with the data presented in this study.
Genetics may influence the risk of muscle injury in women football players, with a focus on tendon and ligament injuries. A recent study found that variations in the COL5A1 rs13946 polymorphism were associated with increased risks of ACL tears and muscle injuries in women’s football players. These variations were associated with differences in ligament laxity between genders, making women football players more susceptible to these injuries [22].
In this regard, the AMPD1 c.34C>T polymorphism in this cohort of women’s amateur football players showed different injury aetiology characteristics from previous studies in men’s professional football players [18]. The CC genotype was more frequent in non-injured players (53.2%) compared to players with the TT genotype (14.3%), an aspect that could present the CC genotype as a protector genotype in tendon and ligament injuries. This is the first time that these results have been presented for women’s football, also showing an association with the severity of injuries in the TT genotype (75.9%), as has been presented in men’s professional football players [18].
Other studies have found that variations in the ACTN3 gene are associated with an increased risk of muscle injury. Specifically, individuals with the TT genotype in the ACTN3 c.1729C>T polymorphism could have an increased risk of muscle strains and tears, which are common injuries in women football players [25,40]. The results presented in this study show a lower severity of injuries in the CC genotype compared to the TT genotype, similar to the data found previously in men’s professional football players [18].
There was an association between match and training injuries in muscle damage genes, such as the CKM c.*800A>G polymorphism, in which, when comparing training and match injuries, it was shown that the GG genotype and G allele lead to higher risks of training injuries in women’s amateur football players. These data differ from those found in a recent study in which no association was found between this polymorphism and the risk of training and match injuries in men’s professional football players [19]. To date, the CKM gene has not been extensively studied in relation to muscle injury, but it has been shown that it can be used for athlete selection due to the effect that the GG genotype has on muscle damage in football players [18,41].
One study found that variations in the MLCK c.37885C>A polymorphism are associated with an increased risk of muscle strains in professional football players [18]. However, this study has shown that this polymorphism, specifically the CA genotype, is associated with match injuries, with the CC genotype being protective for these injury settings, similar to those found in a recent study on men football players in which the CA genotype had a higher risk of injury in matches versus training [18]. The exact mechanisms by which variations in the MLCK gene may influence injury risk are not yet fully understood, and further research is needed to confirm the results found. However, it is thought that these variations may affect the function of smooth muscle cells in the body, including those found in the muscles and connective tissues that are most vulnerable to injury in football [42].
This investigation shows, for the first time, that genetics may be a significant factor in the predisposition to increase the risk of epidemiology in the injuries of women’s amateur football players, especially tendon and ligament injuries, showing new candidate genes associated with the aetiology of these injuries: AMPD1 and ACTN3.
However, this study presents several limitations: (a) the amateur standard of football players recruited for this study may well have confounded these results, as the injuries may have been influenced by lower levels of strength/fitness and/or lower levels of scientific support in this population. Thus, the small effect of individual genetic polymorphisms on injury risk (which is multifactorial even in professional football players) is more likely to be elucidated in a higher standard of football players. (b) Given the small effect size of an individual genetic polymorphism and the multifactorial nature of injury aetiology, the sample size is too low to provide any meaningful information regarding a genetic association with injury. In the future, the author will collect more data by significantly increasing the sample size and conducting a follow-up. (c) Training methods and injury prevention programmes may condition injury risk and be a confounding factor for this study. Finally, (d) future studies could include epigenetic and environmental aspects in the analysis of factors associated with women’s football performance, such as menstrual cycle, to complement the genetic analyses and their applicability in women’s professional football players and to improve and strengthen the links between genetic variations and the knowledge of injuries in this cohort of women football players.
5. Conclusions
This investigation is the first to demonstrate that injury risk and epidemiology in women’s amateur football players is associated with a combination of related genes in muscle injuries. Especially, the TT genotype and the T allele of the AMPD1 c.34C>T polymorphism appears to be the polymorphism that is best associated with tendon/ligament injuries and severity in this cohort of women football players. It has also been shown that the TT genotype of the ACTN3 c.1729C>T polymorphism is associated with injury severity, while the muscle damage-related genes, CKM and MLCK, are associated with injury setting.
The outcomes of this research suggest that the addition of genetic variants previously associated with muscle injury in men football players may serve as a predictor of both muscle and tendon/ligament injury in women football players for the medical and fitness staff. These outcomes also suggest the need to replicate the findings in genetic studies on the aetiology of these injuries in women’s professional/amateur football players.
Funding
This research was funded by the MAPFRE Foundation, Ignacio H. de Larramendi, grant number 6391.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Universidad Francisco de Vitoria (protocol code: 32/2020).
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study. Written informed consent was obtained from the subjects to publish this paper.
Data Availability Statement
The raw data supporting the conclusions of this article will be made available by the authors on request.
Acknowledgments
The author is grateful for the participation of the women football players in this research and wishes to thank the medical staff for their invaluable contribution to the study.
Conflicts of Interest
Author David Varillas-Delgado was employed by the company SPORTNOMICS S.L. Author declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
- Hulteen, R.M.; Smith, J.J.; Morgan, P.J.; Barnett, L.M.; Hallal, P.C.; Colyvas, K.; Lubans, D.R. Global participation in sport and leisure-time physical activities: A systematic review and meta-analysis. Prev. Med. 2017, 95, 14–25. [Google Scholar] [CrossRef] [PubMed]
- Robles-Palazón, F.J.; López-Valenciano, A.; De Ste Croix, M.; Oliver, J.L.; García-Gómez, A.; Sainz de Baranda, P.; Ayala, F. Epidemiology of injuries in male and female youth football players: A systematic review and meta-analysis. J. Sport Health Sci. 2022, 11, 681–695. [Google Scholar] [CrossRef] [PubMed]
- Krustrup, P.; Aagaard, P.; Nybo, L.; Petersen, J.; Mohr, M.; Bangsbo, J. Recreational football as a health promoting activity: A topical review. Scand. J. Med. Sci. Sports 2010, 20 (Suppl. S1), 1–13. [Google Scholar] [CrossRef]
- Hjelm, N.; Werner, S.; Renstrom, P. Injury profile in junior tennis players: A prospective two year study. Knee Surg. Sports Traumatol. Arthrosc. 2010, 18, 845–850. [Google Scholar] [CrossRef]
- Hewett, T.E.; Lindenfeld, T.N.; Riccobene, J.V.; Noyes, F.R. The effect of neuromuscular training on the incidence of knee injury in female athletes. A prospective study. Am. J. Sports Med. 1999, 27, 699–706. [Google Scholar] [CrossRef] [PubMed]
- Kapron, A.L.; Peters, C.L.; Aoki, S.K.; Beckmann, J.T.; Erickson, J.A.; Anderson, M.B.; Pelt, C.E. The prevalence of radiographic findings of structural hip deformities in female collegiate athletes. Am. J. Sports Med. 2015, 43, 1324–1330. [Google Scholar] [CrossRef]
- Nett, B.; Brosky, J.A., Jr.; Velarde, L.; Pariser, D.P.; Boyce, D.A. Selected Musculoskeletal and Performance Characteristics of Members of a Women’s Professional Football Team: Application of a Pre-participation Examination. N. Am. J. Sports Phys. Ther. 2010, 5, 1–15. [Google Scholar]
- Lévesque, J.; Rivaz, H.; Rizk, A.; Frenette, S.; Boily, M.; Fortin, M. Lumbar Multifidus Muscle Characteristics, Body Composition, and Injury in University Rugby Players. J. Athl. Train. 2020, 55, 1116–1123. [Google Scholar] [CrossRef]
- Montalvo, A.M.; Schneider, D.K.; Silva, P.L.; Yut, L.; Webster, K.E.; Riley, M.A.; Kiefer, A.W.; Doherty-Restrepo, J.L.; Myer, G.D. ‘What’s my risk of sustaining an ACL injury while playing football (soccer)?’ A systematic review with meta-analysis. Br. J. Sports Med. 2019, 53, 1333–1340. [Google Scholar] [CrossRef]
- Dick, R.W. Is there a gender difference in concussion incidence and outcomes? Br. J. Sports Med. 2009, 43 (Suppl. S1), i46–i50. [Google Scholar] [CrossRef]
- Prien, A.; Grafe, A.; Rössler, R.; Junge, A.; Verhagen, E. Epidemiology of Head Injuries Focusing on Concussions in Team Contact Sports: A Systematic Review. Sports Med. 2018, 48, 953–969. [Google Scholar] [CrossRef]
- Boling, M.; Padua, D.; Marshall, S.; Guskiewicz, K.; Pyne, S.; Beutler, A. Gender differences in the incidence and prevalence of patellofemoral pain syndrome. Scand. J. Med. Sci. Sports 2010, 20, 725–730. [Google Scholar] [CrossRef] [PubMed]
- Murphy, D.F.; Connolly, D.A.; Beynnon, B.D. Risk factors for lower extremity injury: A review of the literature. Br. J. Sports Med. 2003, 37, 13–29. [Google Scholar] [CrossRef] [PubMed]
- Crossley, K.M.; Patterson, B.E.; Culvenor, A.G.; Bruder, A.M.; Mosler, A.B.; Mentiplay, B.F. Making football safer for women: A systematic review and meta-analysis of injury prevention programmes in 11 773 female football (soccer) players. Br. J. Sports Med. 2020, 54, 1089–1098. [Google Scholar] [CrossRef]
- Martín-San Agustín, R.; Medina-Mirapeix, F.; Esteban-Catalán, A.; Escriche-Escuder, A.; Sánchez-Barbadora, M.; Benítez-Martínez, J.C. Epidemiology of Injuries in First Division Spanish Women’s Soccer Players. Int. J. Environ. Res. Public Health 2021, 18, 3009. [Google Scholar] [CrossRef]
- Lemes, I.R.; Pinto, R.Z.; Lage, V.N.; Roch, B.A.B.; Verhagen, E.; Bolling, C.; Aquino, C.F.; Fonseca, S.T.; Souza, T.R. Do exercise-based prevention programmes reduce non-contact musculoskeletal injuries in football (soccer)? A systematic review and meta-analysis with 13 355 athletes and more than 1 million exposure hours. Br. J. Sports Med. 2021, 55, 1170–1178. [Google Scholar] [CrossRef] [PubMed]
- Kilic, O.; Kemler, E.; Gouttebarge, V. The “sequence of prevention” for musculoskeletal injuries among adult recreational footballers: A systematic review of the scientific literature. Phys. Ther. Sport. 2018, 32, 308–322. [Google Scholar] [CrossRef]
- Maestro, A.; Del Coso, J.; Aguilar-Navarro, M.; Gutiérrez-Hellín, J.; Morencos, E.; Revuelta, G.; Ruiz Casares, E.; Perucho, T.; Varillas-Delgado, D. Genetic profile in genes associated with muscle injuries and injury etiology in professional soccer players. Front. Genet. 2022, 13, 1035899. [Google Scholar] [CrossRef]
- Varillas-Delgado, D.; Morencos, E.; Gutierrez-Hellín, J.; Aguilar-Navarro, M.; Maestro, A.; Perucho, T.; Coso, J.D. Association of the CKM rs8111989 Polymorphism with Injury Epidemiology in Football Players. Int. J. Sports Med. 2023, 44, 145–152. [Google Scholar] [CrossRef]
- Clos, E.; Pruna, R.; Lundblad, M.; Artells, R.; Maffulli, N. ACTN3’s R577X Single Nucleotide Polymorphism Allele Distribution Differs Significantly in Professional Football Players according to Their Field Position. Med. Princ. Pract. 2021, 30, 92–97. [Google Scholar] [CrossRef]
- Maffulli, N.; Margiotti, K.; Longo, U.G.; Loppini, M.; Fazio, V.M.; Denaro, V. The genetics of sports injuries and athletic performance. Muscles Ligaments Tendons J. 2013, 3, 173–189. [Google Scholar] [CrossRef] [PubMed]
- Rodas, G.; Cáceres, A.; Ferrer, E.; Balagué-Dobón, L.; Osaba, L.; Lucia, A.; González, J.R. Sex Differences in the Association between Risk of Anterior Cruciate Ligament Rupture and COL5A1 Polymorphisms in Elite Footballers. Genes 2022, 14, 33. [Google Scholar] [CrossRef] [PubMed]
- Onori, M.E.; Pasqualetti, M.; Moretti, G.; Canu, G.; De Paolis, G.; Baroni, S.; Minucci, A.; Galvani, C.; Urbani, A. Genetics and Sport Injuries: New Perspectives for Athletic Excellence in an Italian Court of Rugby Union Players. Genes 2022, 13, 95. [Google Scholar] [CrossRef]
- Massidda, M.; Voisin, S.; Culigioni, C.; Piras, F.; Cugia, P.; Yan, X.; Eynon, N.; Calò, C.M. ACTN3 R577X Polymorphism Is Associated With the Incidence and Severity of Injuries in Professional Football Players. Clin. J. Sport Med. 2019, 29, 57–61. [Google Scholar] [CrossRef] [PubMed]
- Rodas, G.; Moreno-Pérez, V.; Del Coso, J.; Florit, D.; Osaba, L.; Lucia, A. Alpha-Actinin-3 Deficiency Might Affect Recovery from Non-Contact Muscle Injuries: Preliminary Findings in a Top-Level Soccer Team. Genes 2021, 12, 769. [Google Scholar] [CrossRef] [PubMed]
- Pruna, R.; Artells, R.; Ribas, J.; Montoro, B.; Cos, F.; Muñoz, C.; Rodas, G.; Maffulli, N. Single nucleotide polymorphisms associated with non-contact soft tissue injuries in elite professional soccer players: Influence on degree of injury and recovery time. BMC Musculoskelet. Disord. 2013, 14, 221. [Google Scholar] [CrossRef] [PubMed]
- Varillas-Delgado, D.; Gutierrez-Hellín, J.; Maestro, A. Genetic Profile in Genes Associated with Sports Injuries in Elite Endurance Athletes. Int. J. Sports Med. 2023, 44, 64–71. [Google Scholar] [CrossRef] [PubMed]
- Clarkson, P.M.; Hoffman, E.P.; Zambraski, E.; Gordish-Dressman, H.; Kearns, A.; Hubal, M.; Harmon, B.; Devaney, J.M. ACTN3 and MLCK genotype associations with exertional muscle damage. J. Appl. Physiol. (1985) 2005, 99, 564–569. [Google Scholar] [CrossRef]
- Bisciotti, G.N.; Chamari, K.; Cena, E.; Bisciotti, A.; Corsini, A.; Volpi, P. Anterior cruciate ligament injury risk factors in football. J. Sports Med. Phys. Fitness 2019, 59, 1724–1738. [Google Scholar] [CrossRef]
- Jones, S.; Almousa, S.; Gibb, A.; Allamby, N.; Mullen, R.; Andersen, T.E.; Williams, M. Injury Incidence, Prevalence and Severity in High-Level Male Youth Football: A Systematic Review. Sports Med. 2019, 49, 1879–1899. [Google Scholar] [CrossRef]
- Hägglund, M.; Waldén, M.; Bahr, R.; Ekstrand, J. Methods for epidemiological study of injuries to professional football players: Developing the UEFA model. Br. J. Sports Med. 2005, 39, 340–346. [Google Scholar] [CrossRef] [PubMed]
- Bahr, R.; Clarsen, B.; Derman, W.; Dvorak, J.; Emery, C.A.; Finch, C.F.; Hägglund, M.; Junge, A.; Kemp, S.; Khan, K.M.; et al. International Olympic Committee consensus statement: Methods for recording and reporting of epidemiological data on injury and illness in sport 2020 (including STROBE Extension for Sport Injury and Illness Surveillance (STROBE-SIIS)). Br. J. Sports Med. 2020, 54, 372–389. [Google Scholar] [CrossRef] [PubMed]
- Maestro, A.; Varillas-Delgado, D.; Morencos, E.; Gutiérrez-Hellín, J.; Aguilar-Navarro, M.; Revuelta, G.; Del Coso, J. Injury Incidence Increases after COVID-19 Infection: A Case Study with a Male Professional Football Team. Int. J. Environ. Res. Public Health 2022, 19, 10267. [Google Scholar] [CrossRef] [PubMed]
- Choi, J.H.; Joo, C.H. Match activity profile of professional female soccer players during a season. J. Exerc. Rehabil. 2022, 18, 324–329. [Google Scholar] [CrossRef] [PubMed]
- Larruskain, J.; Lekue, J.A.; Diaz, N.; Odriozola, A.; Gil, S.M. A comparison of injuries in elite male and female football players: A five-season prospective study. Scand. J. Med. Sci. Sports 2018, 28, 237–245. [Google Scholar] [CrossRef]
- López-Valenciano, A.; Ruiz-Pérez, I.; Garcia-Gómez, A.; Vera-Garcia, F.J.; De Ste Croix, M.; Myer, G.D.; Ayala, F. Epidemiology of injuries in professional football: A systematic review and meta-analysis. Br. J. Sports Med. 2020, 54, 711–718. [Google Scholar] [CrossRef] [PubMed]
- Grygorowicz, M.; Wiernicka, M. Systematic Review of Cost-Effectiveness of Injury Prevention Interventions in Soccer-Evidence Why Health Agencies Should Address It. Int. J. Environ. Res. Public Health 2021, 18, 11901. [Google Scholar] [CrossRef]
- Sutton, K.M.; Bullock, J.M. Anterior cruciate ligament rupture: Differences between males and females. J. Am. Acad. Orthop. Surg. 2013, 21, 41–50. [Google Scholar] [CrossRef]
- Larwa, J.; Stoy, C.; Chafetz, R.S.; Boniello, M.; Franklin, C. Stiff Landings, Core Stability, and Dynamic Knee Valgus: A Systematic Review on Documented Anterior Cruciate Ligament Ruptures in Male and Female Athletes. Int. J. Environ. Res. Public Health 2021, 18, 3826. [Google Scholar] [CrossRef]
- Del Coso, J.; Rodas, G.; Buil, M.; Sánchez-Sánchez, J.; López, P.; González-Ródenas, J.; Gasulla-Anglés, P.; López-Samanes, Á.; Hernández-Sánchez, S.; Iztueta, A.; et al. Association of the ACTN3 rs1815739 Polymorphism with Physical Performance and Injury Incidence in Professional Women Football Players. Genes 2022, 13, 1635. [Google Scholar] [CrossRef]
- Varillas-Delgado, D.; Morencos, E.; Gutiérrez-Hellín, J.; Aguilar-Navarro, M.; Muñoz, A.; Mendoza Láiz, N.; Perucho, T.; Maestro, A.; Tellería-Orriols, J.J. Genetic profiles to identify talents in elite endurance athletes and professional football players. PLoS ONE 2022, 17, e0274880. [Google Scholar] [CrossRef] [PubMed]
- Hong, F.; Haldeman, B.D.; Jackson, D.; Carter, M.; Baker, J.E.; Cremo, C.R. Biochemistry of smooth muscle myosin light chain kinase. Arch. Biochem. Biophys. 2011, 510, 135–146. [Google Scholar] [CrossRef] [PubMed]
Table 1.
Women’s amateur football players’ demographic characteristics.
| Total | Injured | Non-Injured | p Value | ||
|---|---|---|---|---|---|
| Age, mean (SD) | 23.26 (3.37) | 23.63 (3.31) | 22.43 (4.13) | 0.459 | |
| Weight, mean (SD) | 60.78 (6.08) | 60.15 (5.88) | 61.62 (6.55) | 0.853 | |
| Height, mean (SD) | 163.91 (5.18) | 164.15 (4.99) | 163.10 (5.46) | 0.673 | |
| BMI, mean (SD) | 22.63 (5.03) | 22.15 (4.88) | 23.32 (5.31) | 0.771 | |
| Position | Goalkeeper, n (%) | 16 (9.5) | 7 (7.5) | 9 (12.0) | 0.239 |
| Defenders, n (%) | 49 (29.2) | 28 (30.1) | 21 (28.0) | ||
| Midfields, n (%) | 67 (39.9) | 34 (36.5) | 33 (44.0) | ||
| Forwards, n (%) | 36 (21.4) | 24 (25.9) | 12 (16.0) |
SD: standard deviation.
Table 2.
Genotype frequencies in women´s amateur football players.
| Gene | Polymorphism | dbSNP | Genotype | Women Football Players, n (%) | |
|---|---|---|---|---|---|
| ACE | Angiotensin-converting enzyme | I/D | rs4646994 | DD | 86 (51.2) |
| ID | 57 (33.9) | ||||
| II | 25 (14.9) | ||||
| ACTN3 | alpha-actinin-3 | c.1729C>T | rs1815739 | CC | 47 (27.9) |
| CT | 96 (57.2) | ||||
| TT | 25 (14.9) | ||||
| AMPD1 | Adenosine monophosphate deaminase 1 | c.34C>T | rs17602729 | CC | 125 (74.4) |
| CT | 29 (17.2) | ||||
| TT | 14 (8.4) | ||||
| CKM | Muscle-specific creatine kinase | c.*800A>G | rs8111989 | GG | 22 (13.1) |
| GA | 75 (44.6) | ||||
| AA | 71 (42.3) | ||||
| MLCK | Myosin light-chain kinase | c.49C>T | rs2700352 | CC | 111 (66.1) |
| CT | 50 (29.7) | ||||
| TT | 7 (4.2) | ||||
| Myosin light-chain kinase | c.37885C>A | rs28497577 | AA | 7 (4.2) | |
| CA | 18 (10.7) | ||||
| CC | 143 (85.1) |
Table 3.
Injury characteristics in women´s amateur football players during the 2022/2023 season.
| Frequency, n (%) | ||
|---|---|---|
| Onset | Acute | 160 (94.7) |
| Repetitive/overuse | 9 (5.3) | |
| Injury setting | Match | 99 (58.6) |
| Training | 70 (41.4) | |
| Tissue affected | Bone | 3 (1.8) |
| Joints and ligaments | 92 (54.4) | |
| Muscles and tendons | 73 (43.2) | |
| Skin | 0 (0.0) | |
| Nervous system | 1 (0.6) | |
| Other | 0 (0.0) | |
| Severity | Slight | 70 (41.4) |
| Mild | 26 (15.4) | |
| Moderate | 44 (26.0) | |
| Severe | 29 (17.2) | |
| Type | Fracture | 0 (0.0) |
| Other bone injuries | 3 (1.8) | |
| Luxation/subluxation | 9 (5.3) | |
| Ligamentous distension | 55 (32.5) | |
| Ligamentous tear | 15 (8.9) | |
| Meniscus injury | 3 (1.8) | |
| Chondral injury | 1 (0.6) | |
| Synovitis | 0 (0.0) | |
| Fasciitis | 0 (0.0) | |
| Muscle tear | 47 (27.8) | |
| Muscle contracture | 23 (13.6) | |
| Tendon strain | 3 (1.8) | |
| Tendon rupture | 0 (0.0) | |
| Bursitis | 0 (0.0) | |
| Tendinitis | 10 (5.9) | |
| Hematoma contusion | 0 (0.0) | |
| Abrasion | 0 (0.0) | |
| Incised wound | 0 (0.0) | |
| Concussion | 0 (0.0) | |
| Dental injuries | 0 (0.0) | |
| Nerve injury | 0 (0.0) | |
| Other injuries | 0 (0.0) | |
| Recurrency | No | 143 (84.6) |
| Yes | 26 (15.4) |
Table 4.
Genotype distribution in women’s amateur football players for total injuries, musculoskeletal and tendon/ligament injuries.
Table 4.
Genotype distribution in women’s amateur football players for total injuries, musculoskeletal and tendon/ligament injuries.
| Injured | Musculoskeletal Injuries | Tendon/Ligament Injuries | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Polymorphism | Genotype | No, n (%) | Yes, n (%) | p Value | df | No, n (%) | Yes, n (%) | p Value | df | No, n (%) | Yes, n (%) | p Value | df | |
| ACE | I/D | DD | 40 (53.3) | 46 (49.5) | 0.275 | 4 | 38 (38.4) | 35 (50.0) | 0.682 | 35 (45.4) | 35 (38.0) | 0.756 | 10 | |
| ID | 30 (40.0) | 27 (29.0) | 42 (42.4) | 26 (37.1) | 8 | 31 (40.3) | 38 (41.3) | |||||||
| II | 5 (6.7) | 20 (21.5) | 19 (19.2) | 9 (12.9) | 11 (14.3) | 19 (20.7) | ||||||||
| ACTN3 | c.1729C>T | CC | 20 (26.7) | 27 (29.0) | 0.966 | 35 (35.4) | 22 (31.4) | 0.364 | 27 (35.1) | 23 (25.0) | 0.700 | 8 | ||
| CT | 43 (57.3) | 53 (57.0) | 11 | 53 (53.5) | 44 (62.8) | 3 | 41 (53.2) | 58 (63.1) | ||||||
| TT | 12 (16.0) | 13 (14.0) | 11 (11.1) | 4 (5.8) | 9 (11.8) | 11 (11.9) | ||||||||
| AMPD1 | c.34C>T | CC | 61 (81.3) | 64 (68.8) | 0.219 | 54 (54.5) | 26 (37.1) | 0.317 | 41 (53.2) ↑ | 4 (4.3) ↓ | 0.003 | 3 | ||
| CT | 14 (18.7) | 15 (16.1) | 2 | 28 (28.3) | 31 (44.3) | 12 | 25 (32.5) | 57 (62.0) | ||||||
| TT | 0 (0.0) | 14 (15.1) | 17 (17.2) | 13 (18.6) | 11 (14.3) ↓ | 31 (33.7) ↑ | ||||||||
| CKM | c.*800A>G | GG | 10 (13.3) | 12 (12.9) | 0.895 | 17 (17.2) | 9 (12.9) | 0.425 | 13 (16.9) | 11 (12.0) | 0.234 | 10 | ||
| GA | 35 (46.7) | 40 (43.0) | 9 | 28 (28.3) | 31 (44.3) | 8 | 30 (39.0) | 23 (25.0) | ||||||
| AA | 30 (40.0) | 41 (44.1) | 54 (54.5) | 30 (42.8) | 34 (44.1) | 58 (63.0) | ||||||||
| MLCK | c.49C>T | CC | 50 (66.7) | 61 (65.6) | 0.597 | 75 (75.7) | 57 (81.4) | 0.686 | 66 (85.7) | 61 (66.3) | 0.135 | 2 | ||
| CT | 25 (33.3) | 25 (26.9) | 2 | 21 (21.3) | 13 (18.6) | 2 | 11 (14.3) | 27 (29.4) | ||||||
| TT | 0 (0.0) | 7 (7.5) | 3 (3.0) | 0 (0.0) | 0 (0.0) | 4 (4.3) | ||||||||
| c.37885C>A | AA | 7 (9.3) | 0 (0.0) | 0.127 | 0 (0.0) | 3 (4.3) | 0.617 | 0 (0.0) | 2 (2.1) | 0.279 | 2 | |||
| CA | 5 (6.7) | 13 (14.0) | 2 | 24 (24.3) | 13 (18.6) | 2 | 14 (18.2) | 25 (27.2) | ||||||
| CC | 63 (84.0) | 80 (86.0) | 75 (75.7) | 54 (77.1) | 63 (81.8) | 65 (70.7) | ||||||||
↑ indicates that the frequency was above the expected value, calculated from the standardised residuals of a chi-square test; ↓ indicates that the frequency was below the expected value, calculated from the standardised residuals of a chi-square test; df, degrees of freedom.
Table 5.
Genotype distribution in women´s amateur football players regarding injury setting and severity.
Table 5.
Genotype distribution in women´s amateur football players regarding injury setting and severity.
| Injury Setting | Severity | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Polymorphism | Genotype | Training, n (%) | Match, n (%) | p Value | df | No, n (%) | Yes, n (%) | p Value | df | |
| ACE | I/D | DD | 23 (32.8) | 47 (47.5) | 0.427 | 55 (39.3) | 14 (48.3) | 0.683 | ||
| ID | 32 (45.7) | 37 (37.4) | 14 | 61 (43.6) | 9 (31.0) | 5 | ||||
| II | 15 (21.5) | 15 (15.1) | 24 (17.1) | 6 (20.7) | ||||||
| ACTN3 | c.1729C>T | CC | 23 (32.8) | 29 (29.3) | 0.937 | 50 (35.7) | 3 (10.3) | <0.001 | ||
| CT | 38 (54.3) | 58 (58.6) | 8 | 85 (60.7) | 11 (37.9) | 4 | ||||
| TT | 9 (12.9) | 12 (12.1) | 5 (3.6) ↓ | 15 (51.8) ↑ | ||||||
| AMPD1 | c.34C>T | CC | 38 (54.3) | 46 (46.5) | 0.465 | 61 (43.6) ↑ | 1 (3.4) ↓ | <0.001 | ||
| CT | 18 (25.7) | 38 (38.4) | 13 | 50 (35.7) | 6 (20.7) | 2 | ||||
| TT | 14 (20.0) | 15 (15.1) | 29 (20.7) ↓ | 22 (75.9) ↑ | ||||||
| CKM | c.*800A>G | GG | 20 (29.2) ↑ | 6 (6.1) ↓ | 0.038 | 20 (14.6) | 5 (17.3) | 0.199 | ||
| GA | 23 (33.3) | 32 (32.3) | 5 | 38 (27.1) | 13 (44.8) | 4 | ||||
| AA | 27 (37.5) | 61 (61.6) | 82 (58.3) | 11 (37.9) | ||||||
| MLCK | c.49C>T | CC | 52 (74.3) | 75 (75.8) | 0.843 | 114 (81.4) | 17 (58.6) | 0.238 | ||
| CT | 15 (21.4) | 20 (20.2) | 2 | 23 (16.4) | 12 (41.4) | 2 | ||||
| TT | 3 (4.3) | 4 (4.0) | 3 (2.1) | 0 (0.0) | ||||||
| c.37885C>A | AA | 1 (1.4) | 2 (2.0) | 0.024 | 2 (1.4) | 2 (6.7) | 0.301 | |||
| CA | 5 (7.1) ↓ | 30 (30.3) ↑ | 2 | 33 (23.6) | 9 (31.0) | 2 | ||||
| CC | 64 (91.5) | 67 (67.7) | 105 (75.0) | 18 (62.3) | ||||||
↑ indicates that the frequency was above the expected value, calculated from the standardised residuals of a chi-square test; ↓ indicates that the frequency was below the expected value, calculated from the standardised residuals of a chi-square test; df, degrees of freedom.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
MDPI and ACS Style
Varillas-Delgado, D. Genes Associated with Muscle, Tendon and Ligament Injury Epidemiology in Women’s Amateur Football Players. Appl. Sci. 2024, 14, 1980. https://doi.org/10.3390/app14051980
AMA Style
Varillas-Delgado D. Genes Associated with Muscle, Tendon and Ligament Injury Epidemiology in Women’s Amateur Football Players. Applied Sciences. 2024; 14(5):1980. https://doi.org/10.3390/app14051980
Chicago/Turabian StyleVarillas-Delgado, David. 2024. "Genes Associated with Muscle, Tendon and Ligament Injury Epidemiology in Women’s Amateur Football Players" Applied Sciences 14, no. 5: 1980. https://doi.org/10.3390/app14051980
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
