VEGFA and KDR gene variants as potential markers of endurance performance and sports-related injuries: A systematic review

Karolina Jabłońska-Paszko; Katarzyna Krawczak-Wójcik; Ewelina Maculewicz

doi:10.2478/bhk-2026-0013

.blurhash-client-img { display: none !important; }

VEGFA and KDR gene variants as potential markers of endurance performance and sports-related injuries: A systematic review

Biomedical Human Kinetics

Volume 18 (2026): Issue 1 (January 2026)

By: Karolina Jabłońska-Paszko , Katarzyna Krawczak-Wójcik and Ewelina Maculewicz

Open Access

|May 2026

Abstract

Study aim

Genetic predisposition influences athletic performance and susceptibility to sports injuries. Single nucleotide polymorphisms (SNPs) in VEGFA and KDR (VEGFR2) genes affect oxygen delivery, vascular adaptation, and tissue regeneration, potentially impacting endurance and injury risk. However, research on these effects remains limited. This systematic review examines the association of VEGFA and KDR SNPs with endurance performance and anterior cruciate ligament (ACL) injury susceptibility in athletes.

Methods

A systematic literature search was conducted in PubMed, Scopus, Web of Science, and EBSCO databases. Eligible studies were case-control designs involving athletes and examining VEGFA or KDR SNPs in relation to endurance performance or ACL injuries. Selection was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seven studies met the criteria.

Results

The VEGFA rs2010963 polymorphism was linked to elite athlete status, with the C allele associated with higher VO₂max and power output (Wmax). The KDR rs1870377 A allele was more frequent in endurance athletes. Regarding injuries, the rs2010963 CC genotype correlated with a higher risk of ACL rupture, while the VEGFA A–A–G haplotype (rs699947, rs1570360, rs2010963) showed a protective effect. A VEGFA rs35569394 polymorphism increased ACL injury risk in I allele carriers.

Conclusion

These findings suggest VEGFA and KDR polymorphisms may modulate aerobic performance and ACL injury risk. Further research is needed to validate these associations and improve genetic profiling in sports science.

References

Ahmetov, I. I., Hakimullina, A. M., Popov, D. V., Lyubaeva, E. V., Missina, S. S., Vinogradova, O. L., Williams, A. G., & Rogozkin, V. A. (2009). Association of the VEGFR2 gene His472Gln polymorphism with endurance-related phenotypes. European Journal of Applied Physiology, 107(1), 95–103. doi: 10.1007/s00421-009-1105-7.
Open DOI Search in Google Scholar Back to article
Ahmetov, I. I., Khakimullina, A. M., Popov, D. V., Missina, S. S., Vinogradova, O. L., & Rogozkin, V. A. (2008). Polymorphism of the vascular endothelial growth factor gene (VEGF) and aerobic performance in athletes. Human Physiology, 34(4), 477. doi: 10.1134/S0362119708040129.
Open DOI Search in Google Scholar Back to article
Aziz, A., Uddin, M. S., Millat, S., & Islam, M. S. (2022). Vascular endothelial growth factor A (VEGFA) promoter rs2010963 polymorphism and cancer risk: An updated meta-analysis and trial sequential analysis. Meta Gene, 31, 101017. doi: 10.1016/j.mgene.2022.101017.
Open DOI Search in Google Scholar Back to article
Baker, J. (2011). Do genes predict potential? Genetic factors and athletic success. In Talent identification and development in sport. Routledge.
Search in Google Scholar Back to article
Balberova, O. V., Bykov, E. V., Sidorkina, E. G., Petrova, M. M., & Shnayder, N. A. (2022). Genetic biomarkers of cardiovascular and cerebrovascular reserves in athletes. Personalized Psychiatry and Neurology, 2(2), 2. doi: 10.52667/2712-9179-2022-2-2-3-27.
Open DOI Search in Google Scholar Back to article
Berardi, R., Brunelli, A., Pagliaretta, S., Paolucci, V., Conti, A., Goteri, G., Refai, M., Pompili, C., Marcantognini, G., Morgese, F., Ballatore, Z., Savini, A., De Lisa, M., Caramanti, M., Santoni, M., Zizzi, A., Piva, F., Mazzanti, P., Onofri, A., …, & Cascinu, S. (2015). Impact of VEGF, VEGFR, PDGFR, HIF and ERCC1 gene polymorphisms on thymic malignancies outcome after thymectomy. Oncotarget, 6(22), 19305–19315. doi: 10.18632/oncotarget.4191.
Open DOI Search in Google Scholar Back to article
Bloor, C. M. (2005). Angiogenesis during exercise and training. Angiogenesis, 8(3), 263–271. doi: 10.1007/s10456-005-9013-x.
Open DOI Search in Google Scholar Back to article
Bonsignore, M. R., Morici, G., Riccioni, R., Huertas, A., Petrucci, E., Veca, M., Mariani, G., Bonanno, A., Chimenti, L., Gioia, M., Palange, P., & Testa, U. (2010). Hemopoietic and angiogenetic progenitors in healthy athletes: Different responses to endurance and maximal exercise. Journal of Applied Physiology, 109(1), 60–67. doi: 10.1152/japplphysiol.01344.2009.
Open DOI Search in Google Scholar Back to article
Buroker, N. E. (2014). VEGFA rSNPs, transcriptional factor binding sites and human disease. The Journal of Physiological Sciences, 64(1), 73–76. doi: 10.1007/s12576-013-0293-4.
Open DOI Search in Google Scholar Back to article
Buroker, N. (2015). VEGFA SNPs (rs34357231 & rs35569394), transcriptional factor binding sites and human disease. British Journal of Medicine and Medical Research, 10(12), 1–11. doi: 10.9734/BJMMR/2015/19777.
Open DOI Search in Google Scholar Back to article
Chen, Y., Dawes, P. T., & Mattey, D. L. (2012). Polymorphism in the vascular endothelial growth factor A (VEGFA) gene is associated with serum VEGF-A level and disease activity in rheumatoid arthritis: Differential effect of cigarette smoking. Cytokine, 58(3), 390–397. doi: 10.1016/j.cyto.2012.02.018.
Open DOI Search in Google Scholar Back to article
Cięszczyk, P., Willard, K., Gronek, P., Zmijewski, P., Trybek, G., Gronek, J., Weber-Rajek, M., Stastny, P., Petr, M., Lulińska-Kuklik, E., Ficek, K., Kemeryte-Riaubiene, E., Maculewicz, E., & September, A. V. (2017). Are genes encoding proteoglycans really associated with the risk of anterior cruciate ligament rupture? Biology of Sport, 34(2), 97–103. doi: 10.5114/biolsport.2017.64582.
Open DOI Search in Google Scholar Back to article
Di Stefano, A. L., Labussiere, M., Lombardi, G., Eoli, M., Bianchessi, D., Pasqualetti, F., Farina, P., Cuzzubbo, S., Gallego-Perez-Larraya, J., Boisselier, B., Ducray, F., Cheneau, C., Moglia, A., Finocchiaro, G., Marie, Y., Rahimian, A., Hoang-Xuan, K., Delattre, J. Y., Mokhtari, K., & Sanson, M. (2015). VEGFA SNP rs2010963 is associated with vascular toxicity in recurrent glioblastomas and longer response to bevacizumab. Journal of Neuro-Oncology, 121(3), 499–504. doi: 10.1007/s11060-014-1677-x.
Open DOI Search in Google Scholar Back to article
Eider, J., Leońska-Duniec, A., Maciejewska-Skrendo, A., Sawczuk, M., Ficek, K., Sawczyn, S., & Cieszczyk, P. (2013). The VEGFR2 gene His472Gln polymorphism in Polish endurance athletes. International Sportmed Journal, 14, 29–35.
Search in Google Scholar Back to article
El Azzouzi, M., El Ahanidi, H., Hafidi Alaoui, C., Chaoui, I., Benbacer, L., Tetou, M., Hassan, I., Bensaid, M., Oukabli, M., Ameur, A., Al Bouzidi, A., Attaleb, M., & El Mzibri, M. (2023). The evaluation of vascular endothelial growth factor A (VEGFA) and VEGFR2 receptor as prognostic biomarkers in bladder cancer. Diagnostics, 13, 1471. doi: 10.3390/diagnostics13081471.
Open DOI Search in Google Scholar Back to article
Facemire, C. S., Nixon, A. B., Griffiths, R., Hurwitz, H., & Coffman, T. M. (2009). Vascular endothelial growth factor receptor 2 (VEGFR2) controls blood pressure by regulating nitric oxide synthase expression. Hypertension, 54(3), 652–658. doi: 10.1161/HYPERTENSIONAHA.109.129973.
Open DOI Search in Google Scholar Back to article
Feldmann, D. C., Rahim, M., Suijkerbuijk, M. A. M., Laguette, M. J. N., Cieszczyk, P., Ficek, K., Huminska-Lisowska, K., Häger, C. K., Stattin, E., Nilsson, K. G., Alvarez-Rumero, J., Eynon, N., Feller, J., Tirosh, O., Posthumus, M., Chimusa, E. R., Collins, M., & September, A. V. (2022). Investigation of multiple populations highlight VEGFA polymorphisms to modulate anterior cruciate ligament injury. Journal of Orthopaedic Research, 40(7), 1604–1612. doi: 10.1002/jor.25192.
Open DOI Search in Google Scholar Back to article
Ferreira, C. P., Silvino, V. O., Trevisano, R. G., de Moura, R. C., Almeida, S. S., & Pereira dos Santos, M. A. (2024). Influence of genetic polymorphism on sports talent performance versus non-athletes: A systematic review and meta-analysis. BMC Sports Science, Medicine and Rehabilitation, 16(1), 223. doi: 10.1186/s13102-024-01001-5.
Open DOI Search in Google Scholar Back to article
Hussain, N., Mumtaz, M., Adil, M., Nadeem, A. A., Sarwar, A., Aziz, T., Alharbi, M., Alshammari, A., Alasmari, A. F., & Alharbi, M. E. (2023). Investigation of VEGF (rs 699947) polymorphism in the progression of Rheumatoid Arthritis (RA) and in-silico nanoparticle drug delivery of potential phytochemicals to cure RA. Acta Biochimica Polonica, 70(3), 3. doi: 10.18388/abp.2020_6654.
Open DOI Search in Google Scholar Back to article
Juginović, A., Kekić, A., Aranza, I., Biloš, V., & Armanda, M. (2025). Next-generation approaches in sports medicine: The role of genetics, omics, and digital health in optimizing athlete performance and longevity – a narrative review. Life, 15(7), 1023. doi: 10.3390/life15071023.
Open DOI Search in Google Scholar Back to article
Karamysheva, A. F. (2008). Mechanisms of angiogenesis. Biochemistry (Moscow), 73(7), 751–762. doi: 10.1134/S0006297908070031.
Open DOI Search in Google Scholar Back to article
Kim, D. H., Xu, W., Kamel-Reid, S., Liu, X., Jung, C. W., Kim, S., & Lipton, J. H. (2010). Clinical relevance of vascular endothelial growth factor (VEGFA) and VEGF receptor (VEGFR2) gene polymorphism on the treatment outcome following imatinib therapy. Annals of Oncology, 21(6), 1179–1188. doi: 10.1093/annonc/mdp452.
Open DOI Search in Google Scholar Back to article
Kissane, R. W. P., & Egginton, S. (2019). Exercise-mediated angiogenesis. Current Opinion in Physiology, 10, 193–201. doi: 10.1016/j.cophys.2019.06.005.
Open DOI Search in Google Scholar Back to article
Komar, A. A. (2007). Silent SNPs: Impact on gene function and phenotype. Pharmacogenomics, 8(8), 1075–1080. doi: 10.2217/14622416.8.8.1075.
Open DOI Search in Google Scholar Back to article
Lin, M., Whitmire, S., Chen, J., Farrel, A., Shi, X., & Guo, J. (2017). Effects of short indels on protein structure and function in human genomes. Scientific Reports, 7(1), 9313. doi: 10.1038/s41598-017-09287-x.
Open DOI Search in Google Scholar Back to article
Liu, X., Zhu, B., Li, Y., Liu, X., Guo, S., Wang, C., Li, S., & Wang, D. (2021). The role of vascular endothelial growth factor in tendon healing. Frontiers in Physiology, 12, 766080. doi: 10.3389/fphys.2021.766080.
Open DOI Search in Google Scholar Back to article
Lulińska-Kuklik, E., Leźnicka, K., Humińska-Lisowska, K., Moska, W., Michałowska-Sawczyn, M., Ossowski, Z., Maculewicz, E., Cięszczyk, P., Kaczmarczyk, M., Ratkowski, W., Ficek, K., Zmijewski, P., & Leońska-Duniec, A. (2018). The VEGFA gene and anterior cruciate ligament rupture risk in the Caucasian population. Biology of Sport, 36(1), 3–8. doi: 10.5114/biolsport.2018.78902.
Open DOI Search in Google Scholar Back to article
Ma, W., Xin, K., Chen, K., Tang, H., Chen, H., Zhi, L., & Liu, H. (2018). Relationship of common variants in VEGFA gene with osteonecrosis of the femoral head: A Han Chinese population based association study. Scientific Reports, 8(1), 16221. doi: 10.1038/s41598-018-34352-4.
Open DOI Search in Google Scholar Back to article
Melincovici, C. S., Bo, A. B., Mihu, C., Istrate, M., Moldovan, I. M., Roman, A. L., & Mihu, C. M. (2018). Vascular endothelial growth factor (VEGF) – key factor in normal and pathological angiogenesis. Romanian Journal of Morphology & Embryology, 59(2), 455–467.
Search in Google Scholar Back to article
Metzger, C. S., Koutsimpelas, D., & Brieger, J. (2015). Transcriptional regulation of the VEGF gene in dependence of individual genomic variations. Cytokine, 76(2), 519–526. doi: 10.1016/j.cyto.2015.07.015.
Open DOI Search in Google Scholar Back to article
Molloy, T., Wang, Y., & Murrell, G. A. C. (2003). The roles of growth factors in tendon and ligament healing. Sports Medicine, 33(5), 381–394. doi: 10.2165/00007256-200333050-00004.
Open DOI Search in Google Scholar Back to article
Paradowska-Gorycka, A., Pawlik, A., Romanowska-Prochnicka, K., Haladyj, E., Malinowski, D., Stypinska, B., Manczak, M., & Olesinska, M. (2016). Relationship between VEGF gene polymorphisms and serum VEGF protein levels in patients with rheumatoid arthritis. Plos One, 11(8), e0160769. doi: 10.1371/journal.pone.0160769.
Open DOI Search in Google Scholar Back to article
Patel, S., & Varley, I. (2019). Exploring the regulation of genetic testing in sport. Entertainment and Sports Law Journal, 17(1), 5. doi: 10.16997/eslj.223.
Open DOI Search in Google Scholar Back to article
Pickering, C., Kiely, J., Grgic, J., Lucia, A., & Del Coso, J. (2019). Can genetic testing identify talent for sport? Genes, 10(12), 12. doi: 10.3390/genes10120972.
Open DOI Search in Google Scholar Back to article
Rahim, M., Gibbon, A., Hobbs, H., van der Merwe, W., Posthumus, M., Collins, M., & September, A. (2014). The association of genes involved in the angiogenesis-associated signaling pathway with risk of anterior cruciate ligament rupture. Journal of Orthopaedic Research, 32(12), 1612–1618. doi: 10.1002/jor.22705.
Open DOI Search in Google Scholar Back to article
Rahim, M., Hobbs, H., Van Der Merwe, W., Posthumus, M., Collins, M., & September, A. V. (2018). Investigation of angiogenesis genes with anterior cruciate ligament rupture risk in a South African population. Journal of Sports Sciences, 36(5), 551–557. doi: 10.1080/02640414.2017.1322710.
Open DOI Search in Google Scholar Back to article
Rahim, M., Lacerda, M., Collins, M., Posthumus, M., & September, A. V. (2022). Risk modelling further implicates the angiogenesis pathway in anterior cruciate ligament ruptures. European Journal of Sport Science, 22(4), 650–657. doi: 10.1080/17461391.2021.1884750.
Open DOI Search in Google Scholar Back to article
Rivron, N. C., Vrij, E. J., Rouwkema, J., Le Gac, S., Van Den Berg, A., Truckenmüller, R. K., & Van Blitterswijk, C. A. (2012). Tissue deformation spatially modulates VEGF signaling and angiogenesis. Proceedings of the National Academy of Sciences, 109(18), 6886–6891. doi: 10.1073/pnas.1201626109.
Open DOI Search in Google Scholar Back to article
Roth, S. M. (2012). Critical overview of applications of genetic testing in sport talent identification. Recent Patents on DNA & Gene Sequences, 6(3), 247–255. doi: 10.2174/187221512802717402.
Open DOI Search in Google Scholar Back to article
Shastry, B. S. (2009). SNPs: Impact on gene function and phenotype. In A. A. Komar (Ed.), Single nucleotide polymorphisms: Methods and protocols (pp. 3–22). Humana Press. doi: 10.1007/978-1-60327-411-1_1.
Open DOI Search in Google Scholar Back to article
Shibuya, M. (2011). Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: A crucial target for anti- and pro-angiogenic therapies. Genes & Cancer, 2(12), 1097–1105. doi: 10.1177/1947601911423031.
Open DOI Search in Google Scholar Back to article
Shukla, M., Gupta, R., Pandey, V., Rochette, J., Dhandapany, P. S., Tiwari, P. K., & Amrathlal, R. S. (2020). VEGFA promoter polymorphisms rs699947 and rs35569394 are associated with the risk of anterior cruciate ligament ruptures among Indian athletes: A cross-sectional study. Orthopaedic Journal of Sports Medicine, 8(12), 2325967120964472. doi: 10.1177/2325967120964472.
Open DOI Search in Google Scholar Back to article
Stevens, A., Soden, J., Brenchley, P. E., Ralph, S., & Ray, D. W. (2003). Haplotype analysis of the polymorphic human vascular endothelial growth factor gene promoter1. Cancer Research, 63(4), 812–816.
Search in Google Scholar Back to article
Takahashi, H., & Shibuya, M. (2005). The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clinical Science, 109(3), 227–241. doi: 10.1042/CS20040370.
Open DOI Search in Google Scholar Back to article
Ysabel, T., Spiteri, T., Hart, N. H., & Anderton, R. S. (2018). The potential role of genetic markers in talent identification and athlete assessment in elite sport. Sports, 6(3), 3. doi: 10.3390/sports6030088.
Open DOI Search in Google Scholar Back to article

Articles in this issue

DOI: https://doi.org/10.2478/bhk-2026-0013 | Journal eISSN: 2080-2234

Journal RSS Feed

Language: English

Page range: 125 - 137

Submitted on: Nov 3, 2025

Accepted on: Mar 30, 2026

Published on: May 6, 2026

Published by: University of Physical Education in Warsaw

In partnership with: Paradigm Publishing Services

Publication frequency: 1 issue per year

Keywords:

Vascular Endothelial Growth Factor Receptor 2,

Related subjects:

Basic medical science,

Basic medical science, other,

Clinical medicine,

Public health,

Sports and recreation,

Sports and recreation, other,

Physical education

© 2026 Karolina Jabłońska-Paszko, Katarzyna Krawczak-Wójcik, Ewelina Maculewicz, published by University of Physical Education in Warsaw
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Volume 18 (2026): Issue 1 (January 2026)