The Influence of the MDR1 C3435T Polymorphism on Methotrexate Responsiveness in Rheumatoid Arthritis Patients

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Background: Methotrexate (MTX) is most widely used for the treatment of rheumatoid arthritis (RA). However, different clinical responses have been observed in patients treated with MTX. Objective: The aim of the work was to determine the influence of the MDR1 C3435T polymorphism on Methotrexate responsiveness in RA patients. Patients and Methods: A cross sectional study included 90 RA patients. Demographics, clinical features, medication history, and the disease activity score (DAS28) were carefully recorded. Genotypes of the C3435T polymorphism were determined by real time polymerase chain reaction for all patients. According to disease activity score, patients were classified into 2 groups: group (1): MTX responders (DAS28 score ≤3.2) and group (2): MTX non-responders (DAS28 score >3.2). Results: Of the 90 RA patients, 80 were females (88.9%) and 10 were males (11.1%). No statistically significant difference was found in genotype or allele frequencies between MTX responders and non-responders groups. However, patients who had C allele were 1.65 times more likely to be non-responder to MTX treatment when compared to those who had the T allele. The most common MTX adverse effects reported were Gastrointestinal upset in 31.1% followed by undesirable hair loss in 11.1%. The probability of having GIT adverse effects was observed to be higher among the cases with (CT) genotype than the other genotypes but without statistical significance. Conclusion: It could be concluded that no significant association could be detected between MDR1 gene C3435T polymorphism and responsiveness to methotrexate in the studied rheumatoid arthritis patients.

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