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

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 χ ² 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). Conclusions: 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.