Matrix Metalloproteinase Polymorphisms as Genetic Risk Factors for Anterior Cruciate Ligament Injuries in Football Players: A Case–Control Study

Background/Objectives: Injuries to the anterior cruciate ligament (ACL) frequently occur in physically active populations and often lead to long-term complications, such as osteoarthritis and recurrent injury. The ACL's structural integrity depends on extracellular matrix (ECM) remodeling, regulated by matrix metalloproteinases (MMPs). This study examined the association between three polymorphisms-MMP1 rs1799750, MMP10 rs486055, and MMP12 rs2276109-and ACL injury outcomes, including injury frequency, strain, partial rupture, and complete rupture. Methods: A total of 296 physically active, unrelated Caucasian males participated in this case-control study, including 160 with ACL injuries (classified as ACLF-ACL injury frequency, ACLS-strain, ACLRP-partial rupture, ACLRC-complete rupture, and ACL-general ACL injury) and 136 healthy controls (CON) with no previous ACL injuries. All injuries resulted from non-contact mechanisms. Results: The MMP1 rs1799750 polymorphism showed a protective effect against ACL injury compared to controls (OR = 0.42, 95% CI: 0.21-0.85, Padj = 0.014). Within the injury group, MMP10 rs486055 was significantly associated with partial ruptures, especially in heterozygous carriers (OR = 3.47, 95% CI: 1.64-7.33, p = 0.001). The MMP12 rs2276109 variant, under a dominant model, was linked to higher injury frequency (OR = 3.80, 95% CI: 1.69-8.54, p = 0.0009) but showed no association with injury severity. Conclusions: The MMP1 rs1799750 polymorphism showed a protective effect against ACL injury, MMP10 rs486055 was associated with an increased risk of partial rupture, and MMP12 rs2276109 was linked to higher injury frequency. These findings highlight the complex genetic and biomechanical interactions underlying ACL injuries. The MMP1 rs1799750 polymorphism showed a protective effect (58% reduction in the odds compared to controls) against ACL injury, MMP10 rs486055 was associated with an increased risk (3.47 times higher odds) of partial rupture, and MMP12 rs2276109 was linked to 3.8 times higher odds of an injury. Identifying genetic risk factors may support personalized injury prevention and rehabilitation strategies, offering new opportunities to reduce long-term complications in athletes and active individuals.