Polymorphisms of methotrexate metabolism genes—as predictors of its hepatotoxicity in rheumatoid arthritis
https://doi.org/10.31146/1682-8658-ecg-178-6-106-111
Abstract
Objective: to identify among the allelic polymorphisms of the folate cycle genes: RFC-1 80G> A, MTHFR C677T and A1298C, TS2R/3R and 6bp del/ins, GGH-401C>T, MDR1 C3435T, hepatotoxicity predictors of methotrexate in patients with rheumatoid arthritis.
Materials and methods: the frequency of liver dysfunction in 85 patients with rheumatoid arthritis was analyzed retrospectively with methotrexate therapy, followed by an assessment of the correlation with allelic polymorphisms of the folate cycle genes that regulate the diff erent stages of drug biotransformation.
Results: an analysis of the distribution of alleles and genotypes of the folate cycle genes mentioned above allowed the identifi cation of protective genetic markers for methotrexate-induced hepatotoxicity in the form of allelic polymorphisms MTHFR1298AC and TS6bp del/ins, as well as suggesting the role of TS6bp ins/ins polymorphism in the development of hyperfermentemia.
Conclusion: the ambiguity of the literature data on the search for prognostic markers of hepatotoxicity of methotrexate, as well as our data, which do not have comparable results in both domestic and foreign publications, dictate the need to continue research on the safety of methotrexate in rheumatoid arthritis.
About the Authors
I. V. Devald
South-Ural State Medical University of the Ministry of Healthcare of the Russian Federation
Russian Federation
Russian Federation
Candidate of Medical Sciences, Associate Professor of the Department for Therapy of the Institute of Additional Professional Education; Associate Professor of the Department of Microbiology, Immunology and General Biology,
454092, Chelyabinsk, Vorovskogo, 64
E. A. Khodus
Professor Kinzerskiy Clinic
Russian Federation
Russian Federation
Rheumatologist,
454087, Chelyabinsk, Bluchera, 53a
K. Yu. Myslivtsova
Professor Kinzerskiy Clinic
Russian Federation
Russian Federation
Rheumatologist,
454087, Chelyabinsk, Bluchera, 53a
E. B. Khromova
Chelyabinsk State University
Russian Federation
Russian Federation
Candidate of Biological Sciences, Associate Professor of the Department of Microbiology, Immunology and General Biology,
454001, Chelyabinsk, Brat’ev Kashirinyh, 129
G. L. Ignatova
South-Ural State Medical University of the Ministry of Healthcare of the Russian Federation
Russian Federation
Russian Federation
Doctor of Medical Sciences, Professor, Head of the Department for Therapy of the Institute of Additional Professional Education,
454092, Chelyabinsk, Vorovskogo, 64
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For citations:
Devald I.V., Khodus E.A., Myslivtsova K.Yu., Khromova E.B., Ignatova G.L. Polymorphisms of methotrexate metabolism genes—as predictors of its hepatotoxicity in rheumatoid arthritis. Experimental and Clinical Gastroenterology. 2020;(6):106-111. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-178-6-106-111
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