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

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.