Variants within the MMP3 and COL5A1 genes associate with soft tissue injury history in elite male rugby athletes

Abstract Objectives To investigate associations between genetic variants within COLGALT1, COL1A1, COL3A1, COL5A1, KDR, MIR608, MMP3, NID1, TIMP2 and VEGFA and injury history in elite male rugby athletes. Design A case-control genetic association study was conducted on 184 elite male rugby athletes. Methods Participants were genotyped for 13 genetic polymorphisms previously associated with soft tissue injury using standard PCR assays. Injury data were collected via a self-reported injury-history questionnaire. Single-locus association and Total Genotype Score (TGS) analyses were conducted using χ² tests. In addition, multifactor dimensionality reduction and inferred haplotype analysis were used to identify genetic interactions. Results The TT genotype of MMP3 rs679620 was underrepresented in the non-injured ligament group compared to the ligament sprain and ligament rupture groups (10%, 32%, 25%; P < 0.04, respectively). The T allele of MMP3 rs679620 was overrepresented in the non-injured tendon group compared to the tendinopathy group (50%, 38%; P < 0.02). The proportion of C allele carriers of COL5A1 rs12722 was higher in the tendon rupture group than the non-injured tendon group (96%, 75%; P < 0.02). Furthermore, the T-C inferred haplotype frequency of COL5A1 rs12722 and COL5A1 rs3196378 was higher in the tendon rupture, ligament sprain and total injured athlete groups compared to their respective non-injured groups (P < 0.02). Conclusion This study is the first to identify associations between MMP3 rs679620 and COL5A1 rs12722 and soft-tissue injury history in elite male rugby athletes. These findings support the growing evidence that soft-tissue injury could be influenced by an athlete's genetic predisposition. Practical implications •Elite rugby athletes carrying the TT genotype of MMP3 rs679620 have an increased risk of ligament injury. •Elite rugby athletes carrying the T-C inferred haplotype of COL5A1 rs12722 and COL5A1 rs3196378 have an increased risk of soft tissue injury. •In the future, these findings may help to develop injury prevention protocols in those with high-risk genetic profiles.