RT Journal Article
T1 Genetic Polymorphisms of GGH and ABCC2 Are Associated with Methotrexate Intolerance in Patients with Rheumatoid Arthritis
A1 Escudero-Contreras, Alejandro
A1 López-Medina, Clementina
A1 Collantes-Estévez, Eduardo
A1 Ortega-Castro, Rafaela
A1 Calvo-Gutiérrez, Jerusalem
A1 Mena-Vázquez, Natalia
A1 Panero-Lamothe, Blanca
A1 Manzanares-Martín, Bárbara
A1 Cáliz-Cáliz, Rafael
A1 Jiménez-Morales, Alberto
A1 Ruiz-Jiménez, Mayte
A1 Font-Ugalde, Pilar
K1 Methotrexate
K1 Rheumatoid arthritis
K1 Genetics
K1 Biomarkers
K1 Metotrexato
K1 Genetic polymorphisms
K1 Genotype
AB Objective: to identify new single-nucleotide polymorphisms (SNPs) in genes encoding proteins involved in methotrexate (MTX) metabolism and to evaluate the associations of these SNPs with MTX toxicity or intolerance in a southern Spanish cohort of patients with rheumatoid arthritis (RA). Methods: An observational, retrospective, and multicenter study was conducted at three participating hospitals in southern Spain. The main variable was intolerance to MTX (i.e., bDMARD monotherapy), defined as an interruption of treatment due to adverse events or toxicity. Patients being treated with MTX and bDMARDs (combined treatment) at the time of the study visit were considered “tolerant” of MTX. Ten polymorphisms were selected for sequencing in our patients according to a literature review. Each polymorphism was classified according to three possible genotypes (e.g., two homozygous (AA or GG) and one heterozygous (AG)), and the association of these combinations with MTX intolerance was evaluated. Results: A total of 227 patients were included in the final analysis (107 intolerant of MTX and 120 tolerant). A significant association was observed between MTX intolerance and the GGH-T401C AA/AG genotype (OR 2.13, 95% CI 1.06–4.29) in comparison with the GG genotype. On the other hand, an inverse association was observed between the ABCC2-C24T TT/TC genotype and intolerance to MTX (OR 0.59, 95% CI 0.35–1.00) in comparison with the CC genotype. Conclusion: This study provides new data on the association between genetic polymorphisms and MTX intolerance, which may contribute to the development of new biomarkers and personalized medicine in patients with RA.
PB MDPI
YR 2021
FD 2021-09-09
LK http://hdl.handle.net/10668/3959
UL http://hdl.handle.net/10668/3959
LA en
NO Escudero-Contreras A, López-Medina C, Collantes-Estévez E, Ortega-Castro R, Calvo-Gutiérrez J, Mena-Vázquez N, et al. Genetic Polymorphisms of GGH and ABCC2 Are Associated with Methotrexate Intolerance in Patients with Rheumatoid Arthritis. J Clin Med. 2021 Sep 9;10(18):4070
DS RISalud
RD Apr 18, 2025