The COL5A1 gene is associated with increased risk of carpal tunnel syndrome

Abstract

The direct causes of idiopathic carpal tunnel syndrome (CTS), a common upper limb entrapment neuropathy, remain unknown. It is however generally accepted that an increase in pressure within the carpal tunnel structure, which contains nine flexor tendons, causes compression of the median nerve. The involvement of these tendons in the aetiology of CTS cannot be excluded. Variants within the collagen, type V, alpha 1 (COL5A1) gene, which encodes for the α1 chain of type V collagen, an important regulator of fibril assembly in tendons, have previously been associated with Achilles tendinopathy. The aim of this study was to determine whether these COL5A1 variants are also associated with CTS. One hundred and three self-reported coloured participants, with a history of carpal tunnel release surgery (CTS) and 150 matched control (CON) participants without any reported history of CTS symptoms were genotyped for the COL5A1 rs13946 (C/T), rs14774622 (C/T)/rs55748801 (G/A) (W/M where W = CG), rs12722 (C/T) and rs71746744 (-/AGGG) variants. The TT genotype of COL5A1 rs13946 was significantly over-represented (p = 0.007) in the CON (69.3 %) compared to that in the CTS (50.6 %) group. When the combined rs14774622/rs55748801 and rs12722 genotypes were analysed, the WW + CC (41.7 %, p = 0.008) and WW + CT (40.3 %, p = 0.009) genotypes were significantly over- and under-represented in the CON group, respectively, when compared to the CTS group (24.5 % WW + CC, 59.2 % WW + CT). Furthermore, the T-W-C (51.2 %, p < 0.001) and C-W-C (15.9 %, p = 0.005) inferred haplotypes were significantly over- and under-represented in the CON compared to the CTS (34.9 % T-W-C, 26.8 % C-W-C). In conclusion, this is the first study to report that variants within the functional COL5A1 3'-untranslated region are associated with the CTS. Further studies are required to replicate these findings.

Interactions BetweenCOL5A1Gene and Risk of the Anterior Cruciate Ligament Rupture

“…The Bst UI RFLP (rs12722) is a common C to T single nucleotide polymorphism (SNP) within the COL5A1 3′ untranslated region which may alter COL5A1 messenger RNA (mRNA) stability ( Laguette et al, 2011 ). Previous studies identified the Bst UI restriction fragment length polymorphism (RFLP) to be associated with chronic Achilles tendinopathy ( Mokone et al, 2006 ; September et al, 2009 ), anterior cruciate ligament ruptures ( O’Connell et al, 2015 ; Posthumus et al, 2009 ; Petr et al, 2014 ), carpal tunnel syndrome ( Burger et al, 2015 ) and properties of the knee ligament ( Kubo et al, 2013 ). In addition, this SNP was also associated with joint flexibility ( Brown et al, 2011 ), joint range of motion (ROM) ( Collins et al, 2009 ) and endurance running performance ( Brown et al, 2011 ; Collins and Posthumus, 2011 ).…”

Mutations in COMP cause familial carpal tunnel syndrome

“…A few nonsyndromic CTS pedigrees with autosomal-dominant inheritance have been reported, but no causal genes or loci were identified 16,17,[20][21][22][23][24][25] . Variants in some genes, including BGN, ACAN, COL5A1, and IL6R, have been associated with the risk of sporadic CTS [26][27][28] . Since environmental factors, such as repetitive hand use, contribute to CTS by preferentially affecting the dominant hand, the high percentage of bilateral CTS (about 60%) 29,30 and twin studies (estimated 46% heritability) 31 suggests that genetic factors significantly influence CTS susceptibility.…”

Biological variation in musculoskeletal injuries: current knowledge, future research and practical implications

“…These variants define two major functional forms of the 3′-UTR, which we have previously termed the C-allelic and T-allelic forms (figure 2B) 42 46. Although not all five of the variants have been genotyped in the studies, considering all the published investigations to date, the C-allelic form appears nevertheless to be under-represented in chronic Achilles tendinopathy,27 42 lateral epicondylitis13 and carpal tunnel syndrome 19. The associated 3′-UTR region does not exactly overlap between all these injuries19 and could reflect the complexity of the biological role the COL5A1 3′-UTR could play in the tissue-specific regulation of type V collagen production.…”

“…As reviewed above, versions of the T-allelic form are associated with several musculoskeletal soft tissue injuries (table 1). 13 19 27 31 42…”