The COL5A1 gene and risk of Achilles tendon pathology in a British cohort

Background: Achilles tendon pathologies (ATPs) such asAchilles tendinopathy and Achilles tendon ruptures have been identified asdebilitating conditions resulting from either acute or repetitive overuseloading mechanisms. ATP is a multifactorial condition for which several geneticrisk factors have been identified. Notably, the COL5A1 rs12722genetic variant has been associated with risk of Achilles tendinopathy in SouthAfrican and Australian populations.1,2 Further, the COL5A1 rs71746744,rs16399 and rs1134170 variants were also associated with Achilles tendinopathywithin combined South African and Australian populations.3 The rs71746744within the 3’-UTR of the COL5A1 gene has been shown to be functional.4

Objective: The objective if this study was toinvestigate if the COL5A1 rs12722 and rs71746744 variants areassociated with ATP in a British (UK) cohort.

Methods: One hundred and thirty six (52 females and 84males) participants diagnosed with Achilles tendon pathology (ATP group) and131 (49 females and 82 males) asymptomatic healthy controls (CON group), wererecruited for this case-control genetic association study. ATP, which includesnon-insertional and insertional Achilles tendinopathy, as well as Achillestendon rupture were diagnosed using MRI scans and ultra-sound imaging. Thisstudy was approved by the Research Ethics committees of the University ofNorthampton and the University of Cape Town and all participants gave writteninformed consent. SNP genotyping was performed using a fluorescence-basedcustom-made TaqMan (rs71746744) and restriction fragment length polymorphismassays (rs12722) from DNA extracted from saliva samples. The significance ofall statistical testing was accepted at p < 0.05.

Results: No significant genotype frequency distributionswere detected in the UK cohort between the CON and ATP groups for the rs12722(p = 0.658) and rs71746744 (p = 0.319) variants. However, when only the maleparticipants were investigated, the TT genotype of the rs12722 (p = 0.015) andthe INS/INS (p = 0.031) of the rs71746744 variant was significantlyover-represented within the ATP groups.

Conclusion: This study showed that both COL5A1rs12722 and rs71746744 variants were significantly associated with risk of ATPwithin males. It is unknown why this association was not found in the femaleparticipants investigated.