title: The association between the COL12A1 gene and anterior cruciate ligament ruptures.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: UCT/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.
authors.forename: Michael
authors.initials: M
authors.lastname: Posthumus
authors.forename: Alison V
authors.initials: AV
authors.lastname: September
authors.forename: Dion
authors.initials: D
authors.lastname: O'Cuinneagain
authors.forename: Willem
authors.initials: W
authors.lastname: van der Merwe
authors.forename: Martin P
authors.initials: MP
authors.lastname: Schwellnus
authors.forename: Malcolm
authors.initials: M
authors.lastname: Collins
mesh_terms: D000328:Adult; D000070598:Anterior Cruciate Ligament Injuries; D024082:Collagen Type XII / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics*; D012421:Rupture / Q000235:genetics; D012727:Sex Characteristics
chemical_list: C547160:COL12A1 protein, human; D024082:Collagen Type XII