Related Experiment Video
Updated: May 12, 2026

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
Association of genetic polymorphisms on methotrexate toxicity in patients with rheumatoid arthritis
María José Zarzuelo Romero1, María Del Mar Maldonado Montoro2, Cristina Pérez Ramírez3
1Department of Pharmacy and Pharmaceutical Technology, Social and Legal Assistance Pharmacy Section, Faculty of Pharmacy, University of Granada, Granada, Spain.
Introduction:
Methotrexate (MTX) is the treatment of choice for patients with rheumatoid arthritis (RA). However, it has been found to produce toxicity in some patients. Different polymorphisms can play a part in inter-individual differences in toxicity. Our aim is therefore to determine the influence of gene polymorphisms in the MTX metabolic pathway, such as MTHFR (rs1801133 and rs1801131), MTHFD1 (rs2236225), MTR (rs1805087), and ABCC2 (rs4148396), on toxicity in MTX treatment among Caucasian patients diagnosed with RA.
Material And Methods:
Real-time polymnerase chain reaction (PCR) analysis with TaqMan probes was performed on these polymorphisms in 200 patients in a retrospective study.
Results:
Patients with TT genotype and C allele for MTHFR rs1801133 gene polymorphism presented a higher risk of anaemia (p = 0.0304; OR = 3.70; 95% CI: 1.10-12.34) and dizziness (p = 0.0438; OR = 8.15; 95% CI: 1.61-148.68). Patients with MTHFR rs1801131-C allele or CC genotype presented a higher risk of mucositis (p = 0.0188; OR = 3.02; 95% CI: 1.22-7.91), acneiform rash (p = 0.0322; OR = 5.74; 95% CI: 1.34-39.21), and alopecia (p = 0.0072; OR = 5.11; 95% CI: 1.37-17.70). Patients with MTR rs1805087-CC genotype presented a higher risk of anosmia (p = 0.0038; OR = 98.00; 95% CI: 3.16-infinite); patients with the TT genotype or T allele for MTHFD1 rs2236225 presented a higher risk of liver failure (p = 0.00229; OR = 2.34; 95% CI: 1.14-4.96) and alopecia (p = 0.0248; OR = 3.83; 95% CI: 1.10-13.30), and patients with the TT genotype for ABCC2 rs4148396 polymorphism (p = 0.0466; OR = 2.67; 95% CI: 0.98-6.94) presented a higher risk of headaches.
Conclusions:
Pharmacogenomic analysis of these polymorphisms may facilitate decision-making in relation to MTX treatment toxicity among RA patients.
Related Concept Videos
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacogenetics of Drug Metabolism: Overview
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Drug toxicity: Idiosyncratic Reactions
