ATIC missense variant affects response to methotrexate treatment in rheumatoid arthritis patients

Pharmacogenomics. 2016 Dec;17(18):1971-1978. doi: 10.2217/pgs-2016-0125. Epub 2016 Nov 25.

Abstract

Aim: The study was aimed at investigation of several gene variants of folate pathway enzymes for their potential association with methotrexate (MTX) treatment response in patients with rheumatoid arthritis.

Patients & methods: Four hundred and twenty two Caucasian patients were classified as good or poor responders, and subsequently genotyped for common SNPs in DHFR, FPGS and ATIC genes.

Results: No significant differences were observed in case of DHFR and FGPS SNPs. As for ATIC rs2372536 (Thr116Ser), GG minor genotype was significantly associated with good response to MTX (OR: 2.40; 95% CI: 1.30-4.42; p = 0.005), which was confirmed by multivariate analysis.

Conclusion: The results of the study suggest that ATIC missense rs2372536 SNP may influence response to MTX therapy in rheumatoid arthritis patients.

Keywords: folate pathway; methotrexate; rheumatoid arthritis.

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Female
  • Humans
  • Hydroxymethyl and Formyl Transferases / genetics*
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Multienzyme Complexes / genetics*
  • Nucleotide Deaminases / genetics*
  • Polymorphism, Single Nucleotide*
  • Tetrahydrofolate Dehydrogenase / genetics

Substances

  • Multienzyme Complexes
  • inosine monophosphate synthase
  • Tetrahydrofolate Dehydrogenase
  • Hydroxymethyl and Formyl Transferases
  • Nucleotide Deaminases
  • Methotrexate