Impact of methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism on the outcome of methotrexate treatment in a sample of Egyptian rheumatoid arthritis patients

Abstract

Background: Methotrexate is the most commonly used disease-modifying anti-rheumatic drug (DMARD) and it is considered the first-line treatment in the management of rheumatoid arthritis (RA). MTX treatment outcome regarding response to the drug and adverse effects in RA patients are not universal. Therefore, it would be beneficial if we could predict the response of patients to MTX before starting MTX treatment in order to determine the patient ' s drug-treatment plan. Objectives: The present study aimed to evaluate the impact of MTHFR A1298C SNP (rs1801131) on the clinical outcome of MTX treatment as regards treatment efficacy and toxicity in a cohort of Egyptian rheumatoid arthritis patients. Patients and methods: Fifty rheumatoid arthritis patients were included in the present study. Data about patient related variables such as age and sex, disease related variables such as disease duration as well as treatment related variables such as treatment duration, dose of MTX, its route of administration and concomitant use of other drugs (NSAIDs) were obtained. DAS28 was calculated to all patients to assess drug response. MTHFR A1298C polymorphism was investigated using real time 5 0 nuclease allelic discrimination assay. Results: Multivariate regression analysis for factors predicting MTX drug response showed that MTHFR A1298C SNP and MTX dose were the most significant independent predictors for MTX treatment response (p = .016, OR = 39.113, 95% C.I = 1.970-776.558, p = .003, OR = 1.667, C.I = 1.184-2.348, respectively). Considering clinicopathological variables; longer disease duration, positive anti-CCP, NSAIDs users, higher MTX doses and longer treatment durations were significantly associated with nonresponse to MTX. Regarding MTX drug toxicity, MTHFR 1298 CC genotype, MTX dose and concomitant use of NSAIDs were significantly associated with MTX drug toxicity (MC p = .003, p = .031, p = .029, respectively). Conclusion: Our study proved that MTHFR A1298C SNP can predict clinical outcome of MTX treatment as regards treatment efficacy and toxicity in Egyptian rheumatoid arthritis patients.

Impact of TYMS gene polymorphism on the outcome of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients – identification of novel single nucleotide polymorphism: Cross-sectional study

“…[19] Patients were divided into 2 groups, in which the responder group was defined as (disease activity score) DAS28 ≤ 3.2, and non-responder DAS28 > 3.2 after at least 3 months of MTX treatment (tablet or parenteral formulations), one reading of DAS28 used to calculate treatment response. [20][21][22] Responder groups included 47 patients and 48 patients as non-responders.…”

Impact of MTHFR gene polymorphism on the outcome of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients

“…Patients were divided into two groups according to a previous study 24 , in which the responder group was defined as DAS28 ≤ 3.2, and the nonresponder DAS28 > 3.2 after at least three months of MTX treatment 24 – 26 . Responder groups included 48 patients and 47 patients as nonresponders.…”

MTHFR Gene Polymorphisms in Iraqi Kurdish Rheumatoid Arthritis Patients: Relation to Methotrexate Response and Toxicity

“…One of the studies done in Indian subjects by Ghodke Puranik et al; explained that RA patients with one dominant Aallele at least (AA or AC of A1298C genotypes) could benefit from MTX treatment when compared with those who have the homozygous recessive genotype CC [29]. On the other hand, Shakari et al showed that homozygous recessive genotype CC and heterozygous genotype AC has a significant association with not responding to MTX drug (p <0.05), and RA patient who were carrying recessive allele C has significant association with not responding to MTX (p <0.05) [18]. In contrast to our result, Grabar et al did not detect any significant association between MTX response and MTHFR A1298C genotypes [33].…”

“…The single SNPs of MTHFR were associated with MTX outcomes in RA. Nevertheless, the results of these studies are controversial and inconclusive [17][18].…”