Influence of type I collagen polymorphisms and risk of anterior cruciate ligament rupture in athletes: a case-control study

Abstract

Background Anterior cruciate ligament (ACL) rupture is a common and severe knee injury in sports and occurs mostly due to noncontact injuries. There is an increasing amount of evidence associating ACL rupture to single nucleotide polymorphisms (SNPs), and SNPs in the collagen type I genes can change its expression and tissue mechanical features. This study aimed to investigate the association between SNPs in COL1A1 and COL1A2 with sports-related ACL tears. Methods A total of 338 athletes from multiple sports modalities were analyzed: 146 were diagnosed with ACL rupture or underwent an ACL reconstruction surgery and 192 have no musculoskeletal injuries. SNPs were genotyped using validated TaqMan assays. The association of the polymorphisms with ACL rupture was evaluated by a multivariable logistic regression model, using odds ratios (OR) and 95% confidence intervals (CI). Results The age, sport modality, and training location were associated with an increased risk of a non-contact ACL tear. COL1A2 SNPs (rs42524 CC and rs2621215 GG) were associated with an increased risk of non-contact ACL injury (6 and 4-fold, respectively). However, no significant differences were detected in the distribution of COL1A1 rs1107946 and COL1A2 rs412777 SNPs between cases and controls. There was a protective association with ACL rupture (OR = 0.25; 95% CI = 0.07–0.96) between COL1A1 rs1107946 (GT or TT) and the wildtype genotypes of the three COL1A2 (rs412777, rs42524, rs2621215). COL1A2 rs42524 and rs2621215 SNPs were associated with non-contact ACL risk. Conclusion The combined analysis of COL1A1-COL1A2 genotypes suggests a gene-gene interaction in ACL rupture susceptibility.

Genetic Determinants of the Anterior Cruciate Ligament Rupture in Sport: An Up-to-Date Systematic Review

“…The A allele of rs1800012 in the COL1A1 gene was more prevalent in the Norwegian than in the Finnish cohort (minor allele frequency: 0.18 vs. 0.14; p < 0.03) (Sivertsen et al, 2019). Perini et al (2022) observed that the COL1A1 SNP (rs1107946, GG or TT) was a protective association with ACLR (OR = 0.25) when the three COL1A2 SNPs (rs412777, rs42524, and rs2621215) were all wildtype. Perini et al (2022) reported that COL1A2 rs42524 (OR = 5.73 [1.22-26.95], and rs2621215 (4.29 [1.26-14.61]) SNPs contributed significantly to the ACL risk between 146 ACLR patients and 192 healthy subjects.…”

Polymorphisms in paired box 1 gene were associated with susceptibility of adolescent idiopathic scoliosis: A case–control study

“…To assure genotyping quality, in each reaction, two standardized negative and positive controls of each polymorphism genotype were used, as previously described. [ 19 ]…”

Are commercial genetic injury tests premature?

“…36 The association of a functional C > A polymorphism (rs1107946) at nucleotide −1997 within the COL1A1 promoter with acute musculoskeletal tissue injuries, as well as its interaction with rs1800012 on the COL1A2 gene, has therefore previously been investigated. 23,24,31,37,38 These other polymorphisms within the regulatory regions of COL1A1 could be more informative in population groups where the rs1800012 T allele is rare or absent. The rs1107946 C allele, which has a frequency of 65% in the Japanese population, has therefore been shown to associate with a higher risk of fatigue fracture and lower risk of muscle injury in female athletes.…”

“…The regulation of COL1A1 , like any other gene, is complex, and the association of other functional COL1A1 polymorphic transcription factor binding sites with musculoskeletal injuries should be considered 36 . The association of a functional C > A polymorphism (rs1107946) at nucleotide −1997 within the COL1A1 promoter with acute musculoskeletal tissue injuries, as well as its interaction with rs1800012 on the COL1A2 gene, has therefore previously been investigated 23,24,31,37,38 . These other polymorphisms within the regulatory regions of COL1A1 could be more informative in population groups where the rs1800012 T allele is rare or absent.…”