THE ROLE OF VARIANTS OF GENETIC POLYMORPHISMS IN PREDICTING THE EFFECTIVENESS OF METHOTREXATE THERAPY IN JUVENILE ARTHRITIS
Abstract
The most common and the most disabling rheumatoid disease in children is juvenile arthritis (JA), this multifactorial disease develops in children under the age of 16, as a result of interactions of genetic and environmental factors [1]. This disease is characterized by a progressive course, accompanied by a significant decrease in the quality of life of patients in childhood and in adulthood.It is important to search for genetic markers for predicting the effectiveness of the use of drugs, primarily methotrexate [1,2]. Methotrexate remains the drug of choice in patients with JA, despite the existence of a number of basic drugs. A large number of clinical studies demonstrate the efficacy, toxicity and resistance of methotrexate therapy, depending on its dose and form of administration. The study of the genotype of patients and the analysis of the correlation with the effectiveness of methotrexate therapy may contribute to the selection of the correct therapeutic dose of the drug.
About the Authors
S. R. Kazantseva
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России
Russian Federation
Russian Federation
L. Sh. Nazarova
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России
Russian Federation
Russian Federation
S. S. Zhukov
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России
Russian Federation
Russian Federation
V. A. Malievsky
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России
Russian Federation
Russian Federation
T. V. Viktorova
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России
Russian Federation
Russian Federation
References
1. Юношеский артрит: клинические рекомендации РФ (Россия) 2013-2017. Союз педиатров России, МЗРФ. - М., 2017. - С. 92
2. A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8/14 protein / Н. Moncrieffe[et al.] // Rheumatology (Oxford). - 2013. № 52. - P.1467-1476
3. Каневская, М.З. Метотрексат в лечении ревматических заболеваний/ М.З. Каневская, С.В. Гурская // Современная ревматология. - 2013. - №4. - С. 47-53
4. Насонов, Е. Фармакотерапия ревматоидного артрита: российские и международные рекомендации / Е.Л. Насонов // Научнопрактическая ревматология. - 2016. - Т. 54, № 5. - С. 557-571
5. Smolen, JS. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update / JS. Smolen [et al.] // Ann Rheum Dis. 2017. - Vol. 76, №6. - Р. 960-77. doi: 10.1136/annrheumdis2016-210715
6. Hinks, A. Association of the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene with response to methotrexate in juvenile idiopathic arthritis /A. Hinks [et al.] // Annals of the Rheumatic Diseases. - 2011. - Vol. 70, № 8. - Р. 1395-1400
7. de Rotte, MC. ABCB1 and ABCC3 gene polymorphisms are associated with first-year response to methotrexate in juvenile idiopathic arthritis / MC. de Rotte // J Rheumatol. - 2012. - №39. - Р. 2032-2040
8. Qiu, Q. Polymorphisms and pharmacogenomics for the toxicity of methotrexate monotherapy in patients with rheumatoid arthritis. A systematic review and meta-analysis/Q Qiu [et al.] // Medicine. - 2017. - Vol. 96, №11. - Р. e6337. doi: 10.1097/MD.0000000000006337
9. Bohanec Grabar, P. Genetic variation in the SLC19A1 gene and methotrexate toxicity in rheumatoid arthritis patients / Bohanec Grabar, P. [et al.] // Pharmacogenomics. - 2012. - Vol. 13, №14. - P. 1583-1594
10. Owen, S.A. Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients / S.A. Owen // Pharmacogenomics J. - 2013. - Vol. 13, № 3. - P. 227-234
11. Plaza-Plaza, J.C. Pharmacogenetic polymorphisms contributing to toxicity induced by methotrexate in the southern Spanish population with rheumatoid arthritis /j.C. Plaza-Plaza [et al.] // OMICS. - 2012. - Vol. 16, № 11. - P. 589-595
12. Девальд И.В. Аллельные полиморфизмы гена тимидилатсинтазы и их гаплотипы как предикторы ответа на метотрексат у больных ревматоидным артритом / И.В. Девальд [и др.] // Научно-практическая ревматология. - 2019. - Т. 57, № 2. - С 149-153
13. Fung, K.L. A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function / K.L. Fung, M.M. Gottesman // Biochim. Biophys. Acta. - 2009. - Vol. 1794, № 5. - P. 860-871
14. Milic, V. Association of dihydrofolate reductase (DHFR)-317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis / V. Milic // Clin. Exp. Rheumatol. - 2012. - Vol. 30, № 2. - P. 178-183
15. Nazarova L.Sh. The relationship of the immune response mediator genes’ polymorphic variants with the methotrexate efficacy in juvenile idiopathic arthritis / L.Sh.Nazarova [et al.] // Turk J Med Sci. - 2020. - Vol. 50. - P.1038-1047
16. Lima, A. Genetic polymorphisms in low-dose methotrexate transporters: current relevance as methotrexate therapeutic outcome biomarkers // A. Lima [et al.] // Pharmacogenomics. - 2014. - Vol. 15, № 12. - P. 14.116
Review
For citations:
Kazantseva S.R., Nazarova L.Sh., Zhukov S.S., Malievsky V.A., Viktorova T.V. THE ROLE OF VARIANTS OF GENETIC POLYMORPHISMS IN PREDICTING THE EFFECTIVENESS OF METHOTREXATE THERAPY IN JUVENILE ARTHRITIS. Bashkortostan Medical Journal. 2021;16(5):45-48. (In Russ.)
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