Studying the relationship of polymorphic variants of the TNF-α, IL-10, IL-6 cytokine genes with the response to methotrexate therapy in juvenile idiopathic arthritis
https://doi.org/10.25557/2073-7998.2023.08.13-19
Abstract
Juvenile idiopathic arthritis (JIA) is ineffective in childhood and adolescence and responds to therapy largely due to genetic differences. The aim of the work was to search for associations of methotrexate therapy in JIA patients with the presence of polymorphic allelic variants of the immune response mediator genes TNF-α rs1800629, IL10 rs1800872 and IL6 rs1800795. The article presents an analysis of the distribution of IL10/IL6 diplotypes and TNF-α/IL10/IL6 triplotypes. The experiments involved 239 patients who received basic therapy with the use of methotrexate. For the purpose of genotyping, the real-time PCR method was used. In the subgroup of RF patients with anegative form of JIA, an association of the polymorphic variant IL10 -592C>A with no effect on methotrexate therapy was found. Ithasbeen established that the presence of one IL10 *A allele increases the likelihood of a lack of response to therapy, while the presence of the *CC genotype increases the chances of a response. A diplotype (IL10*АA/IL6*GC) and a triplotype (TNF-α*GG/IL10*AA/IL6*GC) were identified, which are significantly more common in the general group of patients diagnosed with JIA among patients with no response to methotrexate. It is assumed that the results obtained in further studies can be used as pharmacogenetic predictors of the effectiveness of therapy in patients with JIA.
Keywords
Supporting agencies: The work was carried out as part of the Priority 2030 program.
About the Authors
S. R. Kazantseva
Bashkir State Medical University
Russian Federation
Russian Federation
3, Lenin st., Ufa, 450008
L. Sh. Nazarova
Bashkir State Medical University
Russian Federation
Russian Federation
3, Lenin st., Ufa, 450008
K. V. Danilko
Bashkir State Medical University
Russian Federation
Russian Federation
3, Lenin st., Ufa, 450008
V. A. Malievsky
Bashkir State Medical University
Russian Federation
Russian Federation
3, Lenin st., Ufa, 450008
E. M. Galimova
ФГБОУ ВО Башкирский государственный педагогический университет им. М. Акмуллы
Russian Federation
Russian Federation
3, Lenin st., Ufa, 450008
T. V. Viktorova
Bashkir State Medical University
Russian Federation
Russian Federation
3, Lenin st., Ufa, 450008
References
1. Petty R.E., Southwood T.R., Manners .P, Baum J., Glass D.N, Goldenberg J. et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004; (31):390–392.https://www.jrheum.org/content/31/2/390
2. Yunosheskiy artrit: klinicheskiye rekomendatsii RF (Rossiya) 2013-2017. Soyuz pediatrov Rossii, MZ RF. Moskva [Juvenile arthritis: clinical guidelines of the Russian Federation (Russia) 2013-2017. Union of Pediatricians of Russia, Ministry of Health of the Russian Federation]. Moscow. 2017: 92. (In Russ.)
3. Oberle E.J., Harris J.G., Verbsky J.W. Polyarticular juvenile idiopathic arthritis - epidemiology and management approaches. Clin Epidemiol. 2014;6:379-393. doi:10.2147/CLEP.S53168.
4. Macaubas C., Nguyen K., Milojevic D., Park J.L., Mellins E.D. Oligoarticular and polyarticular JIA: epidemiology and pathogenesis. Nat Rev Rheumatol. 2009;5(11):616-26. doi: 10.1038/nrrheum.2009.209.
5. Barut K., Adrovic A., Şahin S., Kasapçopur Ö. Juvenile Idiopathic Arthritis. Balkan Med J. 2017;34(2):90-101. doi: 10.4274/balkanmedj.2017.0111.
6. Thatayatikom A., Modica R., De Leucio A. Juvenile Idiopathic Arthritis. StatPearls Publishing. 2023 Jan; Available from: https://www.ncbi.nlm.nih.gov/books/NBK554605/.
7. Hersh A.O., Prahalad S. Immunogenetics of juvenile idiopathic arthritis: A comprehensive review. J Autoimmun. 2015;64:113-24. doi: 10.1016/j.jaut.2015.08.002.
8. Mellins E.D., Macaubas C., Grom A.A. Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions. Nat Rev Rheumatol. 2011;7(7):416-26. doi: 10.1038/nrrheum.2011.68.
9. Sedger L.M., McDermott M.F. TNF and TNF-receptors: From mediators of cell death and inflammation to therapeutic giants — past, present and future. Cytokine Growth Factor Rev. 2014;25(4):453–472. doi: 10.1016/j.cytogfr.2014.07.016
10. Nasonov E.L. Dostizheniya revmatologii v XXI v. [Achievements of rheumatology in the XXI century]. Nauchno-prakticheskaya revmatologiya [Scientific and practical rheumatology]. 2014;52(2):133-141. doi.org/10.47360/1995-4484-2022-5-20 (In Russ.)
11. Sen E.S., Dick A.D., Ramanan A.V. Uveitis associated with juvenile idiopathic arthritis. Nat Rev Rheumatol. 2015;11(6):338– 348. doi: 10.1038/nrrheum.2015.20.9
12. Sedger L.M., McDermott M.F. TNF and TNF-receptors: From mediators of cell death and inflammation to therapeutic giants — past, present and future. Cytokine Growth Factor Rev. 2014;25(4):453–472. doi: 10.1016/j.cytogfr.2014.07.016.
13. Ringold S., Angeles-Han S.T., Beukelman T., et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care Res (Hoboken) . 2019;71(6):717-734. doi: 10.1002/acr.23870
14. Yatskiv A.A., Sukalo A.V., Goncharova R.I. Assotsiatsiya polimorfnykh variantov genov immunnogo i vospalitel’nogo otveta, ne otnosyashchikhsya k glavnomu kompleksu gistosovmestimosti, s patologiyey sustavov u detey v Respublike Belarus [Association of polymorphic variants of immune and inflammatory response genes that are not related to the major histocompatibility complex with joint pathology in children in the Republic of Belarus]. Meditsinskaya genetika [Medical genetics]. 2020; 9(9):25–36. https://www.medgen-journal.ru/jour/article/view/1705/1341 (In Russ.)
15. Nazarova L.S., Danilko K.V., Malievsky V.A., et al. The role of the immune response mediator genes polymorphism in the predisposition to juvenile idiopathic arthritis. Russian Open Medical Journal 2019; 8: e0408. Available at: https://cyberleninka.ru/article/n/the-role-of-the-immune-responsemediator-genes-polymorphism-in-the-predisposition-tojuvenile-idiopathic-arthriti
16. Schmeling H., Horneff G. Tumour necrosis factor alpha promoter polymorphisms and etanercept therapy in juvenile idiopathic arthritis. Rheumatol Int. 2007;27(4):383-386. doi: 10.1007/s00296-006-0208-2.
17. Guryeva O.D., Savelyeva M.I., Valiev T.T. Otsenka toksichnosti terapii metotreksatom na osnove farmakogeneticheskogo testirovaniya pri ostrom limfoblastnom leykoze u detey [Evaluation of the toxicity of methotrexate therapy based on pharmacogenetic testing in acute lymphoblastic leukemia in children]. Farmakogenetika i farmakogenomika [Pharmacogenetics and pharmacogenomics]. 2021;(2):6-7. doi.org/10.37489/2588-0527-2021-2-6-7. (In Russ.)
18. Nikishina I.P., Kaleda M.I. Sovremennaya farmakoterapiya sistemnogo yuvenil’nogo artrita [Modern pharmacotherapy of systemic juvenile arthritis]. Nauchno-prakticheskaya revmatologiya [Scientific and practical rheumatology]. 2015;53(1):84-93. (In Russ.)
19. Wallace С.А., Giannini E.H., Huang B., et al. American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis care & research. 2011 Jul;63(7):929-36. doi: 10.1002/acr.20497.
20. McDonald J.H. Handbook of Biological Statistics. 3rd ed. Baltimore, MD, USA: Sparky House Publishing. 2014.
Review
For citations:
Kazantseva S.R., Nazarova L.Sh., Danilko K.V., Malievsky V.A., Galimova E.M., Viktorova T.V. Studying the relationship of polymorphic variants of the TNF-α, IL-10, IL-6 cytokine genes with the response to methotrexate therapy in juvenile idiopathic arthritis. Medical Genetics. 2023;22(8):13-19. (In Russ.) https://doi.org/10.25557/2073-7998.2023.08.13-19
Views:
290
Email this article 