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The association between the COL12A1 gene and anterior cruciate ligament ruptures
  1. Michael Posthumus1,
  2. Alison V September1,
  3. Dion O'Cuinneagain2,
  4. Willem van der Merwe2,
  5. Martin P Schwellnus1,
  6. Malcolm Collins1,3
  1. 1UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
  2. 2Sports Science Orthopaedic Clinic, Cape Town, South Africa
  3. 3The South African Medical Research Council, Cape Town, South Africa
  1. Correspondence to Associate Professor M Collins, UCT/MRC Research Unit for Exercise Science and Sports Medicine, South African Medical Research Council and the University of Cape Town, PO Box 115, Newlands 7725, South Africa; malcolm.collins{at}


Background Anterior cruciate ligament (ACL) ruptures are among the most severe musculoskeletal soft tissue injuries. However, the exact mechanisms which cause these acute injuries are unknown. Recently, sequence variants within two genes, namely COL1A1 and COL5A1, which code for the α1 chains of types I and V collagen respectively, were shown to be associated with ACL ruptures. Type XII collagen, similarly to types I and V collagen, is a structural component of the ligament fibril and is encoded by a single gene, COL12A1.

Objective The aim of this study was to investigate whether sequence variants within COL12A1 are associated with ACL ruptures.

Methods One hundred and twenty-nine (38 female) participants with clinically and surgically diagnosed ACL ruptures, as well as 216 (83 female) physically active controls participants (CON) without any history of ACL injury were included in this case-control genetic association study. All participants were genotyped for the AluI and BsrI restriction fragment length polymorphisms (RFLPs) within COL12A1.

Results The AA genotype of the COL12A1 AluI RFLP was significantly over-represented in the female (OR=2.4, 95% CI 1.0 to 5.5, p=0.048), but not male (p=0.359) ACL participants. There were no genotype differences between the ACL and CON group for the BsrI RFLP.

Conclusion The COL12A1 AluI RFLP is associated with ACL ruptures among female participants in this study. The results suggest that females with an AA genotype are at increased risk of ACL ruptures. These initial genetic association studies should be explored further and, if repeated, incorporated into multifactorial models developed to identify predisposed individuals.

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  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Research Ethic Committee of the Faculty of Health Sciences, University of Cape Town.

  • Patient consent Obtained.