Association of MDR1 C3435T and RFC1 G80A polymorphisms with methotrexate toxicity and response in Jordanian rheumatoid arthritis patients.

Objectives: Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). Genetic polymorphisms of reduced folate carrier (RFC1 G80A) and multi-drug resistance-1 (MDR1 C3435T) might affect MTX response and/or toxicity. The aim of this study was to find out if there is an association between those polymorphisms and MTX toxicity and/or response in Jordanian RA patients.

Method: A genotyping approach was used to determine the studied polymorphisms in 159 RA patients.

Results: There was an association between RFC1 G80A and MDR1 C3435T polymorphisms with MTX toxicity. Patients with RFC1 80GG genotype were at higher risk for gastrointestinal toxicity (p = 0.036). Patients carrying at least one MDR1 3435T variant allele were at higher risk for MTX overall toxicity (p = 0.04), especially hepatotoxicity (p = 0.028). Furthermore, the distribution of RFC1 G80A polymorphism between males and females was significantly different. The variant genotype 80AA was found to be more in males than in females (60% vs. 31%) (p = 0.011).

Conclusions: Our results suggest that genetic polymorphisms in methotrexate transporters affect the toxicity but not the response of MTX treatment. Further studies should be performed to have more conclusive results.