Matrix metalloproteinase genes on chromosome 11q22 and the risk of anterior cruciate ligament (ACL) rupture

• Published in: Scandinavian journal of medicine & science in sports 2012-08, Vol.22 (4), p.523-533
• Main Authors: Posthumus, M., Collins, M., van der Merwe, L., O'Cuinneagain, D., van der Merwe, W., Ribbans, W. J., Schwellnus, M. P., Raleigh, S. M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anterior Cruciate Ligament Injuries; Case-Control Studies; Chromosomes, Human, Pair 11 - genetics; Female; Genes; genetic; Genetic Predisposition to Disease; Humans; Injuries; injury; Knee; Knee Injuries - genetics; Ligaments; Male; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 10 - genetics; Matrix Metalloproteinase 12 - genetics; Matrix Metalloproteinase 3 - genetics; Matrix Metalloproteinases - genetics; Polymorphism; Polymorphism, Single Nucleotide; predisposition; Risk factors; Rupture - genetics; ruptures; tear; Young Adult
• ISSN: 0905-7188; 1600-0838
• DOI: 10.1111/j.1600-0838.2010.01270.x

As matrix metalloproteinases (MMPs) are critical to ligament homeostasis and integrity, the aim of this study was to investigate whether four functional polymorphisms within four MMP genes, which cluster on chromosome 11q22 associate with risk of ACL ruptures. Three hundred and forty‐five [129 with ACL ruptures (ACL group) and 216 asymptomatic controls (CON group)] unrelated Caucasians were recruited for this case‐control study. Fifty‐four participants reported non‐contact mechanisms of ACL rupture (NON subgroup). All participants were genotyped for the MMP10 C/T rs486055, MMP1 1G/2G rs1799750, MMP3 G/A rs679620 and MMP12 A/G rs2276109 variants. After adjusting 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 subgroup (14%), when compared with the CON group (26%). No other variants were significantly different between groups. Adjusted for the same confounders, the two 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 and the ACL groups, and the CON group and the NON subgroup, respectively. This is the first report that indicates an association between the chromosomal region 11q22 and the risk of ACL rupture.