Evaluation of Genetic Marker Polymorphisms (MTHFRC677T and ABCC2 C) for Predicting Methotrexate Toxicity in Psoriasis Patients in Egypt: A Case‐Control Study

Methotrexate is an antineoplastic agent prescribed in various treatment protocols, particularly for psoriasis. Studies on toxicogenomic and clinical data suggest that polymorphism in genes involved in folate metabolism are linked to varying individual responses to methotrexate (MTX). This study aimed to investigate the single nucleotide polymorphisms (SNPs) of two genetic DNA markers (MTHFR 677 C and ABCC2 C), their correlation to protein expression, and laboratory investigations as potential predictors of susceptibility to MTX toxicity among patients. This is a case-control study involving 90 patients treated with methotrexate at the Kasr Al-Ainy psoriasis unit (KAPU), Department of Dermatology. Upon assessing genetic marker polymorphisms, the MTHFR 677 C allele was the most common among all patients (69%). There were more patients with the mutant homozygous (TT) allele in the case group compared to the control group (30% vs. 7%). The ABCC2 C allele was the most prevalent (75%), with the T allele present in 25% of patients. The case group exhibited a lower expression of the CT allele compared to the control group (30% vs. 53%), with a significant difference between the two groups. MTX levels were higher in the case group, while homocysteine levels did not differ significantly between the groups. The C allele of the ABCC2 gene, with a methotrexate cutoff greater than 4.5081 ng/ml, and the MTHFR T polymorphism are strongly associated with toxicity. The risk of toxicity in individuals receiving methotrexate can be predicted with a threshold value of 4.5081 ng/ml for methotrexate levels; however, there was no significant variation in homocysteine levels across the groups.