title: Carpal tunnel syndrome: The role of collagen gene variants.
abstract: BACKGROUND
  The direct causes of idiopathic carpal tunnel syndrome (CTS) are still unknown. It is suggested that pathology of the tendons and other connective tissue structures within the carpal tunnel may play a role in its aetiology. Variants in genes encoding connective tissue proteins, such as type V collagen, have previously been associated with CTS. Since variants within other collagen genes, such as type I, XI and XII collagen, have previously been associated with modulating the risk of musculoskeletal soft tissue injuries, the aim of this study was to determine whether variants within COL1A1, COL11A1, COL11A2 and COL12A1 were associated with CTS.
  
  
  METHODS
  Self-reported Coloured South African participants, with a history of carpal tunnel release surgery (CTS, n=103) and matched control (CON, n=150) participants without any reported history of CTS symptoms were genotyped for COL1A1 rs1800012 (G/T), COL11A1 rs3753841 (T/C), COL11A1 rs1676486 (C/T), COL11A2 rs1799907 (T/A) and COL12A1 rs970547 (A/G).
  
  
  RESULTS
  The TT genotype of COL11A1 rs3753841 was significantly over-represented in the CTS group (21.4%) compared to CON group (7.9%, p=0.004). Furthermore, a trend for the T minor allele to be over-represented in the CTS group (p=0.055) with a significant association when only female participants (p=0.036) were investigated was observed. Constructed inferred pseudo-haplotypes including a previously investigated COL5A1 variant, rs71746744 (-/AGGG), suggest gene-gene interactions between COL5A1 and COL11A1 modulate the risk of CTS.
  
  
  CONCLUSIONS
  These findings provide further information of the role of the genetic risk factors and the possible role of variations in collagen fibril composition in the aetiology of CTS. Genetic factors could potential be included in models developed to identify indivisuals at risk of CTS. Strategies that target modifiable risk factors to mitigate the effect of non-modifiable risk factors, such as the genetic risk, could be also developed to reduce incidence and morbidity of CTS.
authors.affiliation: Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, South Africa.
authors.forename: Suhail
authors.initials: S
authors.lastname: Dada
authors.affiliation: Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, South Africa.
authors.forename: Marilize C
authors.initials: MC
authors.lastname: Burger
authors.affiliation: Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, South Africa.
authors.forename: Franka
authors.initials: F
authors.lastname: Massij
authors.affiliation: Life Occupational Health, Life Healthcare, Cape Town, South Africa.
authors.forename: Hanli
authors.initials: H
authors.lastname: de Wet
authors.affiliation: Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, South Africa. Electronic address: malcolm.collins@uct.ac.za.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Collins
mesh_terms: D000328:Adult; D002349:Carpal Tunnel Syndrome / Q000235:genetics*; D016022:Case-Control Studies; D003094:Collagen / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D003094:Collagen
keywords: CTS; Collagen; Entrapment neuropathy; Genetics; Injury; Median nerve; Wrist