The VEGFA and KDR genes are associated with bilateral and multiple chronic Achilles tendon injuries.

OBJECTIVES

Pain is the primary symptom of Achilles tendinopathy, with neovascularisation implicated in symptom development despite unclear mechanisms. Neovascularisation and pain are regulated by vascular endothelial growth factor A (VEGFA) and its receptor, KDR. Since VEGFA polymorphisms have previously been associated with Achilles tendinopathy, this study aimed to determine whether VEGFA (rs699947 C>A, rs2010963 G>C) and/or KDR (rs2071559 C>T, rs1870377 A>T) polymorphisms are associated with exercise-related pain at injury onset, multiple and/or bilateral injuries, as well as self-reported pain using multidimensional pain scales.

DESIGN

Case-control and cross-sectional genetic association study.

METHODS

One hundred and eighty-nine controls without any history of tendon injuries and 181 participants with Achilles tendinopathy were recruited, of which 71 and 91 reported multiple-bilateral and single-unilateral injuries respectively, and genotyped for KDR and VEGFA. Pain was assessed using the VISA-A, short-form McGill Pain and short-form Brief Pain Inventory questionnaires.

RESULTS

The KDR C-T and T-A (rs2071559, rs1870377) inferred haplotypes were associated with decreased (cases: 32.8%, controls: 44.3%, p = 0.009) and increased (cases: 22.1%, controls: 12.1%, p = 0.007) risk of multiple-bilateral tendinopathy, respectively. The C-C-T and A-T-A VEGFA (rs699947) and KDR (rs2071559, rs1870377) allele combinations were also associated with decreased (cases: 13.1%, controls: 20.9%, p = 0.018) and increased (cases: 14.0%, controls: 6.2%, p = 0.001) risk of multiple-bilateral tendinopathy, respectively. There were no significant differences in pain scores between the genotype groups.

CONCLUSIONS

KDR and VEGF genetic variants are associated with susceptibility to bilateral and/or multiple Achilles tendinopathy, supporting the potential role for angiogenesis signalling pathways in injury risk.