Association of COL5A1 gene polymorphisms and musculoskeletal soft tissue injuries: a meta-analysis based on 21 observational studies

Abstract

Objective Inconsistent findings existed on the correlation of collagen type V α1 (COL5A1) gene polymorphisms and musculoskeletal soft tissue injuries (MSTIs). The purpose of this study was to collect and combine the current evidences by a meta-analysis approach. Methods Six online databases were searched up to August, 2021. The methodological quality of each individual study was evaluated based upon Newcastle–Ottawa Scale (NOS). The strength of the effect size was presented by odds ratio (OR) with 95% confidence interval (95%CI) in five genetic models. The data were analyzed using Review Manager 5.3. Results Twenty-one studies were eligible to this meta-analysis. The study quality was deemed fair to excellent according to NOS. In the overall analyses, the merged data suggested that rs12722, rs71746744, and rs3196378 polymorphisms were correlated to an increased susceptibility to MSTIs. But the association was not established in rs13946 or rs11103544 polymorphism. For rs12722 polymorphism, stratified analyses by injury type and ethnicity identified the association mainly existed in ligament injury and among Caucasian population. For rs13946 polymorphism, subgroup analysis suggested the association existed in tendon and ligament injuries. Conclusion This study supports that rs12722 is associated with an elevated susceptibility to ligament injury, especially in the Caucasian population. Rs13946 polymorphism appears to increase the risk to tendon and ligament injuries. Rs71746744 and rs3196378 polymorphisms have a tendency to confer an elevated risk to MSTIs. However, no relevance is found between rs11103544 polymorphism and MSTIs.

Genetic Variants within NOGGIN, COL1A1, COL5A1, and IGF2 are Associated with Musculoskeletal Injuries in Elite Male Australian Football League Players: A Preliminary Study

“…The COL5A1 gene encodes for the collagen type V α1 chain of protein and forms part of the extracellular matrix of skeletal muscles and can affect passive muscle stiffness as well as joint flexibility [ 56 , 57 ]. The rs12722 polymorphism has also been associated with a higher susceptibility to ligament injuries [ 58 ]. We also found significant associations between the rs12722 TT genotype, contact bone injuries, and moderate severity contact bone injuries.…”

Sex Differences in the Association between Risk of Anterior Cruciate Ligament Rupture and COL5A1 Polymorphisms in Elite Footballers

“…We observed a significant change between sexes in the association between the C-allele and risk of ACL (p = 0.027) (Figure 1A), suggesting a female-specific risk with the presence of the C-allele. As the association between ACL injury and rs13946 has been previously reported [28], we assessed the consistency of our results with those discussed in a recent metaanalysis by Guo et al [28]. In the reported meta-analysis, the frequencies of the alleles conditioned by ACL injury were available for all studies, together with information about whether the studies were on males, females or both.…”

“…The distribution of alleles in the injured groups was similar to that for rs13946; however, the minor allele frequency was higher in the non-injured group, and the association was not significant after correction for the type of model. We performed a similar analysis on rs12722 in COL5A1, which has also been extensively investigated with respect to ACL injury [28]. We observed six, nine and two female footballers with T/T, C/T and C/C alleles and no injuries, respectively, whereas we found three, one and three injuries for T/T, C/T and C/C.…”

“…We observed a significant association between the C/C homozygous genotype for rs13946 and ACL injury in all 46 footballers. We meta-analyzed this result with those from both sexes as described by Guo et al [28]. We reassessed the recessive model on five studies considered in the reported meta-analysis [28] and combined the results with ours for both males and females.…”

“…We meta-analyzed the risk of ACL for men and women using our data and those reported in the meta-analysis by Guo et al [28] from eight different studies. As reported, the studies had significant heterogeneity.…”