Health Science Reviews

By Maxene Rich

Anterior cruciate ligament (ACL) ruptures are considered one of the most critical musculoskeletal soft tissue injuries in the world. They severely impair knee function, require costly surgery, involve long recovery, and increase the risk of re-injury. Due to this, genetic susceptibility to injury has been explored to enable early detection and prevention.

The COL1A1 and COL5A1 genes have been associated with ACL ruptures in many previous studies as they encode collagen types I and V, respectively. Without the proper formation of collagen fibres, ligaments cannot form properly leading to the ligament being more fragile and easily susceptible to rupture. However, the COL12A1, which codes for type XII collagen, had yet to be explored.

Posthumus et al. (2009) conducted a case-control study to explore whether COL12A1 variants are associated with ACL rupture. The study included 129 surgically diagnosed ACL-injured individuals (38 females, 91 males) and 216 healthy, active controls (83 females, 133 males), all of Caucasian descent.

Blood samples were collected in both the case and control groups. DNA from each participant was then extracted, and two single nucleotide polymorphisms (SNPs) located within exons 29 (rs240736, T1738I) and 65 (rs970547, S3058G) of COL12A1 were selected for investigation. Primer pairs (BsrI RFLP for SNP rs240736 and AluI RFLP for SNP rs970547) were designed to amplify the DNA fragments containing each of the two selected SNPs, and genotyping was performed on every case and control sample.

Significance was measured using Hardy-Weinberg equilibrium where a p-value is considered statistically significant when it is less than or equal 0.05. When the female and male participants were analysed together, there were no significant differences in genotype or allele frequencies between the cases and controls. However, when analysing females separately, the AA genotype of the AluI RFLP (rs970547) was significantly more frequent in the case group and was associated with a 2.4-fold increased risk of ACL rupture (p = 0.048). This association was not observed in males. No significant association was found for the BsrI RFLP in either sex.

Reference:

Posthumus, M., September, A.V., O’Cuinneagain, D., van der Merwe, W., Schwellnus, M.P. and Collins, M. (2009). The association between the COL12A1 gene and anterior cruciate ligament ruptures. British Journal of Sports Medicine, 44(16), pp.1160–1165. doi:https://doi.org/10.1136/bjsm.2009.060756.