Role of COL5A1 gene polymorphism (rs12722) in lower limb musculoskeletal injuries among adults - a systematic review and meta analysis

Objective: Musculoskeletal injuries mainly occur in tendons and ligaments and their aetiology is tightly connected with genetic and environmental influences. This review and meta-analysis aimed to identify and evaluate the potential association of the COL5A1 rs12722 polymorphism with lower limb musculoskeletal injuries in adults (18-60 years). 

Methods: A literature search was conducted in three databases (SCOPUS, Web of Science and PubMed) and after screening, nine studies published in the last fifteen years were selected. The data were extracted and interpreted by the main injury types focusing on the effects of genotype distribution (CC, CT, TT) of the rs12722 polymorphism. Meta-analysis was carried out using different modes of inheritance and injury sub-groups. 

Results: Many individual studies indicated no significant difference between cases and controls (p>0.05), but in pooled data, there was a significant association of COL5A1 rs12722 polymorphism with lower limb musculoskeletal risk of injury (p=0.009). The meta-analysis showed a significant effect for the total sample for the recessive model of inheritance (OR =1.28 (CI 1.03-1.57, p=0.021) and ACLI (OR=1.31 (CI 1.03-1.67, p=0.026). 

Conclusions: The systematic review and meta-analyses confirm that T allele carriers (TT, CT) were more susceptible to injury, while the C allele is protective, decreasing the risk of injury.