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AB1703 (2024)
ANALYSIS OF SLCO1B1 VARIANTS AS PREDICTORS OF METHOTREXATE TOLERANCE IN MEXICAN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS
Keywords: Biomarkers, Genetics, Disease-modifying Drugs (DMARDs)
J. Garcia-Silva1, B. Silva-Ramirez2, A. K. Leos-Leija3, V. Mata-Tijerina4, A. Villarreal-Trevino3, N. Rubio3, F. García-Rodriguez5
1Hospital Universitario “José Eleuterio Gonzalez”, UANL, Departamento de Pediatría, Monterrey, Mexico
2Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Departamento de Inmunogenetica, Monterrey, Mexico
3Hospital Universitario “Jose Eleuterio Gonzalez”, UANL, Departamento de Pediatria, Monterrey, Mexico
4Centro de Investigación Biomedica del Noreste, Instituto Mexicano del Seguro Social, Departamento de Inmunogenetica, Monterrey, Mexico
5Hospital Universitario “Jose Eleuterio Gonzalez”, UANL, Departamento de Pediatría, Monterrey, Mexico

Background: Methotrexate (MTX) is the disease-modifying drug of choice for most clinical forms of juvenile idiopathic arthritis (JIA). The most frequent adverse events (AEs) of MTX are gastrointestinal alterations and hepatotoxicity, which can affect adherence to treatment, leading to the activation of the disease. The SLCO1B1 gene codes for a liver protein (OATP1B1) that is responsible for drug transportation. Genetic variation within the SLCO1B1 gene locus impact drug transport, which can lead to altered pharmacokinetic profiles, delayed MTX clearance and increased toxicity.


Objectives: Our aim was to determine the association between Single Nucleotide Polymorphisms (SNPs) in the SLCO1B1 gene (rs4149056, rs2306283) with the presence of AEs in patients with JIA being treated with MTX.


Methods: This is an observational study to analyze the relationship between SNPs of the SLCO1B1 gene and the AEs reported in the clinical record during therapy with MTX in patients with JIA. The SNPs were determined with Real Time-PCR using TaqMan®SNP Assays. The haplotypes were conformed of the two SNPs at *1A, *1B, *5, and *15. Allele frequencies, genotypes and haplotypes were compared using the following programs: https://www.snpstats.net/ and Epi Info V7 https://www.cdc.gov/epiinfo/esp/es_index.html .


Results: Twenty-three Mexican children diagnosed with JIA participates in the study, 17 girls and 6 boys, with a mean age of 11.26 (3-17) years. Fourteen patients (60.86%) presented any AEs, being gastrointestinal alterations the most frequent (13, 92.85%). The distribution of genotypes was found in Hardy-Weinberg equilibrium. The SLCO1B1*1B was associated with the presence of more AEs in the response to MTX in patients with JIA (OR=4.22, 95% CI=1.19 -18.89, p=0.03).


Conclusion: Patients with allele *1B may benefit from lower doses of MTX. SLCO1B1 genotyping is a promising way to identify patients at higher risk of getting AEs during treatment with MTX, allowing individualization of the treatment. Due to the sample size, the results should be interpreted as preliminary and further confirmatory studies in a larger cohort are needed.


REFERENCES: [1] J Roszkiewicz, D Michałek, A Ryk, Z Swacha, B Szmyd & E Smolewska (2020): SLCO1B1 variants as predictors of methotrexate-related toxicity in children with juvenile idiopathic arthritis, Scandinavian Journal of Rheumatology, DOI: 10.1080/03009742.2020.1818821.


Acknowledgements: NIL.


Disclosure of Interests: None declared.

DOI: 10.1136/annrheumdis-2024-eular.2613
Keywords: Biomarkers, Genetics, Disease-modifying Drugs (DMARDs)
Citation: , volume 83, supplement 1, year 2024, page 2227
Session: All Diseases (Publication Only)