Background Anterior cruciate ligament (ACL) rupture is a complex disorder for which several risk factors, including genetic factors, have been established.

Objective As matrix metalloproteinases (MMPs) are critical to ligament homeostasis and integrity, the primary aim of this study was to investigate if four selected polymorphisms within four MMP genes, which cluster on chromosome 11q22, associate with risk of ACL ruptures.

Methods 343 (138 individuals with ACL ruptures (ACL group) and 215 asymptomatic controls (CON group)) unrelated Caucasians were recruited for this case-control genetic association study. The ACL group included 54 participants with a non-contact mechanism of ACL rupture (NON- subgroup). All participants were genotyped using fluorescence-based assays, for the four selected functional polymorphisms; namely the MMP10 C/T rs486055, MMP1 1G/2G rs1799750, MMP3 G/A rs679620 and MMP12 A/G rs2276109 variants.

Results When adjusted for sex, age and weight, the AG and GG genotypes of the MMP12 rs2276109 variant were significantly (p=0.030) under-represented among the NON-subgroups (14%), when compared to the CON group (26%). No other variants were significantly different between groups. In addition, when adjusted for the same confounders, the four variant haplotypes T-1G-A-A (CON 14%, ACL 9%, p=0.033) and C-2G-G-G (CON 14%, NON 5%, p=0.021) were significantly different between the CON group and the ACL group, as well as the CON and NON sub-group, respectively.

Conclusion This study reports for the first time that the chromosomal region 11q22 is associated with risk of ACL rupture. The genetic risk profile reported in this study, together with genetic risk factors previously associated, and those yet to be identified, should in the future be included in multifactorial models designed to reduce the incidence of ACL rupture within ‘at-risk’ populations. Further research is required to replicate these findings in an independent population.