Objectives: A COL5A1 gene variant was shown to be associated with chronic Achilles tendinopathies (TEN) in a South African (SA) population. The aim of this case-control genetic association study was to (i) investigate the BstUI and DpnII restriction fragment length polymorphisms (RFLP) in a second population from Australia and (ii) to identify a predisposing haplotype for TEN in both populations.
Methods: Eighty-five Australian and 93 SA TEN, as well as, 210 Australian and 132 SA control Caucasian subjects were genotyped for the BstUI (rs12722) and DpnII (rs13946) RFLPs, as well as, markers rs10858286, rs3196378, rs11103544, rs4504708 and rs3128575.
Results: The BstUI RFLP (P<0.001), as well as markers rs3196378 (P=0.003) and rs11103544 (P=0.003), were associated with TEN in the Australian cohort. Individuals with a BstUI RFLP CC genotype had a significant decreased risk of developing TEN versus any other genotypes (OR=0.42, 95% CI 0.20-0.86, P=0.017). The TTCT and TTCC haplotypes (rs13946, rs12722, rs3196378 and rs11103544) were inferred to be under- (P=0.038) and over-represented (P<0.001) compared to all other haplotypes, respectively, in the tendinopathy group when the combined Australian and SA cohorts were analysed.
Conclusion: The (i) BstUI RFLP is associated with chronic Achilles tendinopathy in a second population and (ii) a region within COL5A1 3’-UTR may predispose individuals to an increased risk of developing TEN.