Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients

Abstract

Background: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients.

Aim: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX.

Patients & methods: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes.

Results: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively).

Conclusion: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.

Keywords: ABCB1; FPGS; GGH; SLC19A1/RFC1; methotrexate; pharmacogenetics; rheumatoid arthritis.