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The relationship of the immune response mediator genes polymorphic variants with the methotrexate efficacy in juvenile idiopathic arthritis.

ABSTRACT: BACKGROUND/AIM:The aim of the study was to analyze the relationship of the immune response mediator genes polymorphic loci (TNFA rs1800629, LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601, PADI4 rs2240336) variants with the methotrexate efficacy in juvenile idiopathic arthritis (JIA). MATERIALS AND METHODS:The study included 274 JIA patients from the Republic of Bashkortostan, Russia. Achieving the American College of Rheumatology Pediatric 30 (ACR Pedi 30) response was regarded as the presence of the response to methotrexate (otherwise ? as the absence), while achieving clinical remission on medication (Wallace et al., 2011) ? as the sufficient response (otherwise ? as the insufficient). Genotyping was conducted by the real-time polymerase chain reaction. RESULTS:Associations with an altered risk of the non-response to methotrexate in JIA were observed for the alleles/genotypes of the loci IL10 rs1800872 (in girls) and NFKB1 rs28362491 (in girls); with an altered risk of the insufficient response to methotrexate in JIA ? for the alleles/genotypes of the loci IL1B rs16944 (in boys), CTLA4 rs3087243 (in boys), NFKB1 rs28362491 (in girls) and the haplotype TNFA rs1800629*A - LTA rs909253*G (in girls). CONCLUSION:As a result of the study the relationship of the alleles/genotypes of the IL1B rs16944, IL10 rs1800872, CTLA4 rs3087243, NFKB1 rs28362491 polymorphic loci and the TNFA rs1800629*A - LTA rs909253*G haplotype with the methotrexate efficacy in JIA was established (taking into account the differences by sex).

SUBMITTER: Nazarova L

PROVIDER: S-EPMC7379423 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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The relationship of the immune response mediator genes’ polymorphic variants with the methotrexate efficacy in juvenile idiopathic arthritis

Nazarova Liliia L Danilko Ksenia K Malievsky Viktor V Karimov Denis D Bakirov Akhat A Viktorova Tatiana T

Turkish journal of medical sciences 20200623 4

<h4>Background/aim</h4>The aim of the study was to analyze the relationship of the immune response mediator genes’ polymorphic loci (TNFA rs1800629, LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601, PADI4 rs2240336) variants with the methotrexate efficacy in juvenile idiopathic arthritis (JIA).<h4>Materials and methods</h4>The study included 274 ...[more]

PMID: 31958219

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Project description:BackgroundMethotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug in juvenile idiopathic arthritis (JIA). In JIA, it is important to start effective treatment early to avoid long-term sequelae, such as joint damage. To accomplish this goal, it is crucial to know beforehand who is going to respond well to MTX. In addition, MTX adverse effects such as MTX intolerance occur frequently, potentially hindering its efficacy. To avoid inefficacy of an otherwise effective drug, the physician should be timely aware of these adverse events. Consequently, to optimise treatment of JIA patients with MTX, predictors for efficacy and adverse events should be used in daily clinical practice. The aim of this study was to summarise the existing knowledge about such predictors.MethodsA systematic literature search was performed in PubMed, Embase and The Cochrane Library, and 1,331 articles were identified. These were selected based on their relevance to the topic and critically appraised according to pre-defined criteria. Predictors for MTX efficacy and adverse events were extracted from the literature and tabulated.ResultsTwenty articles were selected. The overall quality of the studies was good. For MTX efficacy, candidate predictors were antinuclear antibody positivity, the childhood health assessment questionnaire score, the myeloid-related protein 8/14 level, long-chain MTX polyglutamates, bilateral wrist involvement and some single nucleotide polymorphisms (SNPs) in the adenosine triphosphate binding cassette and solute carrier transporter gene families. For MTX adverse events, potential predictors were alanine aminotransferase and thrombocyte level and two SNPs in the γ-glutamyl hydrolase and methylenetetrahydrofolate reductase genes. However, validation of most predictors in independent cohorts was still lacking.ConclusionsInteresting candidate predictors were found, especially for MTX efficacy. However, most of these were not validated. This should be the goal of future efforts. A clinically relevant way to validate the predictors is by means of creating a clinical prediction model.

Dataset Information

The relationship of the immune response mediator genes polymorphic variants with the methotrexate efficacy in juvenile idiopathic arthritis.

Publications

The relationship of the immune response mediator genes’ polymorphic variants with the methotrexate efficacy in juvenile idiopathic arthritis

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