Role of Methotrexate Polyglutamation and Reduced Folate Carrier 1 (RFC1) Gene Polymorphisms in Clinical Assessment Indexes

DOI Web Site Web Site PubMed 2 Citations 19 References
  • ANDO Yukie
    Department of Clinical Pharmacokinetics, Graduate School of Kyushu University
  • SHIMADA Hideaki
    Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University
  • MATSUMOTO Nozomi
    Department of Clinical Pharmacokinetics, Graduate School of Kyushu University
  • HIROTA Takeshi
    Department of Clinical Pharmacokinetics, Graduate School of Kyushu University
  • ORIBE Motohiro
    Oribe Rheumatism and Internal Medicine Clinic
  • OTSUKA Eiji
    Otsuka Internal Medicine and Rheumatism Clinic
  • ISHII Kohji
    Department of Internal Medicine I, Faculty of Medicine, Oita University
  • MORIMOTO Takuya
    Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University
  • OHASHI Kyoichi
    Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University
  • IEIRI Ichiro
    Department of Clinical Pharmacokinetics, Graduate School of Kyushu University

Search this article

Description

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.<br>

Journal

Citations (2)*help

See more

References(19)*help

See more

Keywords

Details 詳細情報について

Report a problem

Back to top