Role of methotrexate polyglutamation and reduced folate carrier 1 (RFC1) gene polymorphisms in clinical assessment indexes

Yukie Ando, Hideaki Shimada, Nozomi Matsumoto, Takeshi Hirota, Motohiro Oribe, Eiji Otsuka, Kohji Ishii, Takuya Morimoto, Kyoichi Ohashi, Ichiro Ieiri

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The aims of the present study were to define inter-individual differences in response to methotrexate (MTX) through MTX polyglutamate (MTX-PG) levels in red blood cells (RBC) and MTX-related gene polymorphisms. A total of 145 rheumatoid arthritis patients were recruited. MTX-PG1-5 concentrations in RBC were measured, and 11 single nucleotide polymorphisms, all in MTX-related genes involved in the folate pathway, were analyzed. Disease activity was also assessed. There was no direct relationship between any MTX-PG concentration and the patient's disease condition, but detectability of MTX-PG5 was extracted as a candidate marker for response to MTX. When disease activity was compared between patients in which MTX-PG5 was detectable and undetectable, all indexes except the visual analog scale (VAS) and C-reactive protein (CRP) were found to be significantly lower in the former patients. Reduced folate carrier 1 (RFC1) 80G>A was significantly associated with the detectability of MTX-PG5; detectability of MTX-PG5 was lower in patients with the A mutant allele. The present study suggests that detectability of MTX-PG5 in RBC is a possible biomarker for response to MTX, and the RFC1 80G>A mutation is associated with low detectability of MTX-PG5. Prospective studies with a sufficient number of patients are needed to confirm the present findings.

Original languageEnglish
Pages (from-to)442-445
Number of pages4
JournalDrug metabolism and pharmacokinetics
Volume28
Issue number5
DOIs
Publication statusPublished - Jan 1 2013

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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