ABCC1, ABCG2 and FOXP3: Predictive Biomarkers of Toxicity from Methotrexate Treatment in Patients Diagnosed with Moderate-to-Severe Psoriasis

Cristina Membrive-Jiménez; Sayleth Vieira-Maroun; Noelia Márquez-Pete; Yasmin Cura; Cristina Pérez-Ramírez; Jesús Tercedor-Sánchez; Alberto Jiménez-Morales; María Del Carmen Ramírez-Tortosa

doi:10.3390/biomedicines11092567

ABCC1, ABCG2 and FOXP3: Predictive Biomarkers of Toxicity from Methotrexate Treatment in Patients Diagnosed with Moderate-to-Severe Psoriasis

Biomedicines. 2023 Sep 19;11(9):2567. doi: 10.3390/biomedicines11092567.

Authors

Cristina Membrive-Jiménez¹, Sayleth Vieira-Maroun¹, Noelia Márquez-Pete¹, Yasmin Cura¹, Cristina Pérez-Ramírez^{1

2}, Jesús Tercedor-Sánchez³, Alberto Jiménez-Morales⁴, María Del Carmen Ramírez-Tortosa²

Affiliations

¹ Pharmacogenetics Unit, Pharmacy Service, University Hospital Virgen de las Nieves, 18014 Granada, Spain.
² Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, 18011 Granada, Spain.
³ Dermatology Service, University Hospital Virgen de las Nieves, 18014 Granada, Spain.
⁴ Hospital Pharmacy Department, University Hospital Virgen de las Nieves, 18014 Granada, Spain.

Abstract

Background: Methotrexate (MTX) is one of the most extensively used drugs in the treatment of moderate-to-severe psoriasis (PS). However, it frequently must be suspended owing to the toxicity in certain patients.

Objective: To evaluate the influence of ABCC1, ABCG2, and FOXP3 in the development of MTX toxicity in PS.

Methods: Retrospective cohort study with 101 patients. Five single-nucleotide polymorphisms (SNPs) were genotyped using real-time polymerase chain reaction with TaqMan probes.

Results: Patients carrying ABCC1 rs2238476-AG genotype (AG vs. GG: OR = 8.04; 95% CI = 1.48-46.78; p = 0.015); FOXP3 rs376154-GT and GG genotypes (GT vs. TT/GG: OR = 3.86; 95% CI = 1.17-13.92; p = 0.031) and ABCG2 rs13120400-T allele (T vs. CC: OR = 8.33; 95% CI = 1.24-164.79; p = 0.059) showed a higher risk of developing more than one adverse effect. The toxicity analysis by subtypes showed that the ABCC1 rs2238476-AG genotype (AG vs. GG: OR = 8.10; 95% CI = 1.69-46.63; p = 0.011) and FOXP3 rs376154-GT genotype (OR = 4.11; 95% CI = 1.22-15.30; p = 0.027) were associated with the appearance of asthenia. No association of the other ABCC1 polymorphisms (rs35592 and rs246240) with MTX toxicity was found.

Conclusion: ABCC1, ABCG2, and FOXP3 polymorphisms can be considered to be risk biomarkers of toxicities in PS patients treated with MTX.

Keywords: adverse drug reactions; adverse events; genetic polymorphisms; hepatotoxicity; methotrexate; pharmacogenetics; psoriasis; toxicity.

Grants and funding

This research was partly supported by a contract for Cristina Membrive-Jiménez from the Fundación de Investigación Biosanitaria de Andalucía Oriental (FIBAO) and the University of Granada. The Virgen de las Nieves University Hospital Biobank was supported by grants co-funded by ERDF funds (EU) from The Instituto de Salud Carlos III (PT13/0010/0039).