THE VEGFA AND KDR GENES ARE ASSOCIATED WITH BILATERAL OR MULTIPLE CHRONIC ACHILLES TENDON INJURIES

Author(s): COLLINS, M., BRAZIER, C.D., MKUMBUZI, N.S., SEPTEMBER, A.V., LANGUETTE, M.J.N., Institution: UNIVERSITY OF CAPE TOWN, Country: SOUTH AFRICA, Abstract-ID: 709

INTRODUCTION:
Chronic Achilles tendinopathy (AT) is prevalent in athletes, specifically in sports with a large running component. It presents as swelling, impaired lower limb function and pain. Although the mechanisms are unclear, current theories implicate structural changes and neovascularisation in AT. Vascular endothelial growth factor (VEGF) and its receptor referred to as kinase domain receptor (KDR) are key regulators of neovascularisation and can be associated with pain. Polymorphisms within the VEGFA and KDR genes have previously been associated with musculoskeletal soft tissue injuries. The primary aim of this study was to identify whether VEGF and KDR polymorphisms were associated with (i) the severity of AT, (ii) AT ultrasound findings and (iii) self-reported measurements of Achilles tendon pain using multidimensional pain scales.
METHODS:
185 recreational athletes with clinically confirmed AT were recruited from Cape Town, South Africa. The injured and uninjured Achilles tendons were examined using conventional grayscale ultrasound. Tendinopathy pain was rated by completing the VISA-A, Short-form McGill Pain Questionnaire (sf- MPQ), and Short-form Brief Pain Inventory (sf-BPI) questionnaires. 194 asymptomatic healthy appropriately matched individuals with no history of tendon injuries were also recruited for this study. Participants were genotyped for VEGFA (rs699947, C/A; rs2010963, G/A) and KDR (rs2071559, G/C; rs1870377, T/A).
RESULTS:
The VEGFA rs699947 CC genotype was significantly associated with decreased risk of bilateral AT, while the A-G VEGFA inferred haplotype constructed from rs699947 and rs2010963 was associated with increased risk of bilateral AT. The KDR rs2071559 AA genotype was significantly associated with increased risk of a history of multiple (two or more) AT, while the G-T and A-A KDR inferred haplotypes constructed from rs2071559 and rs1870377 were associated with decreased risk and increased risk of multiple and/or bilateral AT, respectively. The C-G and A-A VEGFA rs699947 and KDR rs2071559 allele-allele interactions were significantly associated with decreased and increased risk of bilateral or multiple injuries respectively. There were no significant differences in the diameters or the relative number of abnormal ultrasound findings of the injured and uninjured Achilles tendons between the VEGFA and KDR genotype groups. Finally, there were also no significant differences in VISA-A, sf-MPQ and sf-BPI scores, as well the sub-scale scores between the genotype groups.
CONCLUSION:
The novel findings of this study implicate the VEGF and KDR genes, and by implication the potential biological role of the angiogenesis signalling pathway, with bilateral and/or multiple Achilles tendinopathy risk. The investigated variants within these genes however were not associated with tendon diameters, the relative number of abnormal ultrasound findings or self-reported Achilles tendon pain measured using multidimensional pain scales.