title: Variants within the MMP3 gene are associated with Achilles tendinopathy: possible interaction with the COL5A1 gene.
abstract: OBJECTIVE
  Sequence variation within the COL5A1 and TNC genes are known to associate with Achilles tendinopathy. The primary aim of this case-control genetic association study was to investigate whether variants within the matrix metalloproteinase 3 (MMP3) gene also contributed to both Achilles tendinopathy and Achilles tendon rupture in a Caucasian population. A secondary aim was to establish whether variants within the MMP3 gene interacted with the COL5A1 rs12722 variant to raise risk of these pathologies.
  
  
  METHODS
  114 subjects with symptoms of Achilles tendon pathology and 98 healthy controls were genotyped for MMP3 variants rs679620, rs591058 and rs650108.
  
  
  RESULTS
  As single markers, significant associations were found between the GG genotype of rs679620 (OR = 2.5, 95% CI 1.2 to 4.90, p = 0.010), the CC genotype of rs591058 (OR = 2.3, 95% CI 1.1 to 4.50, p = 0.023) and the AA genotype of rs650108 (OR = 4.9, 95% CI 1.0 to 24.1, p = 0.043) and risk of Achilles tendinopathy. The ATG haplotype (rs679620, rs591058, and rs650108) was under-represented in the tendinopathy group when compared to the control group (41% vs 53%, p = 0.038). Finally, the G allele of rs679620 and the T allele of COL5A1 rs12722 significantly interacted to raise risk of AT (p = 0.006). No associations were found between any of the MMP3 markers and Achilles tendon rupture.
  
  
  CONCLUSIONS
  Variants within the MMP3 gene are associated with Achilles tendinopathy. Furthermore, the MMP3 gene variant rs679620 and the COL5A1 marker rs12722 interact to modify the risk of tendinopathy. These data further support a genetic contribution to a common sports related injury.
authors.affiliation: Division of Health and Life Sciences, University of Northampton, Park Campus, Boughton Green Road, Northampton NN2 7AL, UK. Stuart.Raleigh@northampton.ac.uk
authors.forename: S M
authors.initials: SM
authors.lastname: Raleigh
authors.forename: L
authors.initials: L
authors.lastname: van der Merwe
authors.forename: W J
authors.initials: WJ
authors.lastname: Ribbans
authors.forename: R K W
authors.initials: RK
authors.lastname: Smith
authors.forename: M P
authors.initials: MP
authors.lastname: Schwellnus
authors.forename: M
authors.initials: M
authors.lastname: Collins
mesh_terms: D000125:Achilles Tendon; D000328:Adult; D016022:Case-Control Studies; D024062:Collagen Type V / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D052256:Tendinopathy / Q000235:genetics*
chemical_list: C530725:COL5A1 protein, human; D024062:Collagen Type V; D019278:Matrix Metalloproteinase 3