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

研究成果: ジャーナルへの寄稿記事

10 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)442-445
ページ数4
ジャーナルDrug metabolism and pharmacokinetics
28
発行部数5
DOI
出版物ステータス出版済み - 1 1 2013

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Reduced Folate Carrier Protein
Methotrexate
Genes
Erythrocytes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

これを引用

Role of methotrexate polyglutamation and reduced folate carrier 1 (RFC1) gene polymorphisms in clinical assessment indexes. / Ando, Yukie; Shimada, Hideaki; Matsumoto, Nozomi; Hirota, Takeshi; Oribe, Motohiro; Otsuka, Eiji; Ishii, Kohji; Morimoto, Takuya; Ohashi, Kyoichi; Ieiri, Ichiro.

:: Drug metabolism and pharmacokinetics, 巻 28, 番号 5, 01.01.2013, p. 442-445.

研究成果: ジャーナルへの寄稿記事

Ando, Yukie ; Shimada, Hideaki ; Matsumoto, Nozomi ; Hirota, Takeshi ; Oribe, Motohiro ; Otsuka, Eiji ; Ishii, Kohji ; Morimoto, Takuya ; Ohashi, Kyoichi ; Ieiri, Ichiro. / Role of methotrexate polyglutamation and reduced folate carrier 1 (RFC1) gene polymorphisms in clinical assessment indexes. :: Drug metabolism and pharmacokinetics. 2013 ; 巻 28, 番号 5. pp. 442-445.
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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.",
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AU - Oribe, Motohiro

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