The Impact of ATIC (rs2372536) Polymorphism on Responsiveness to and Toxicity of Methotrexate (MTX) in Rheumatoid Arthritis

Abstract

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by ongoing inflammation of the synovial membranes and chronic aggressive arthritis. Despite significant advances in RA treatment in recent years, the total remission rate remains concerning and once bone or joint tissue has been destroyed, it is so hard to return to its original status.Objective : The current study aimed to examine the impact of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) rs 2372536 C >G polymorphism on the responsiveness and toxicity of methotrexate treatment in Egyptian rheumatoid arthritis patients.Methods: This cross-sectional study was performed on 50 rheumatoid arthritis patients. They were selected within the Rheumatology department at Ain Shams University Hospitals from January 2022 to January 2023. The enrolled patients were categorized into two groups in accordance to their response to methotrexate treatment: responders and non-responders. Determination of ATIC gene (rs 2372536) polymorphism was done by real-time PCR for all participants.Results: After 3 months of methotrexate therapy, the enrolled patients were divided into 25 responders and 25 non-responders. ATIC gene rs 2372536 C >G showed a relationship to failure of response to methotrexate treatment in the recessive model [GG vs. (CC+CG)] (p = 0.018). Also, the G allele was substantially found more in the non-responders (p= 0.045). Our study found no significant association between ATIC gene rs 2372536 C >G s polymorphism and the toxicity related to MTX.Conclusion: Our results showed that ATIC gene rs 2372536 C >G polymorphism is linked to failure to react to methotrexate therapy in Egyptian rheumatoid arthritis patients but has no association with vulnerability to toxicity from the treatment.