2016 Fiscal Year Final Research Report
Pharmacogenetic study of methotrexate in patients with rheumatoid arthritis.
| Project/Area Number |
26461477
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Toho University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | メトトレキサート / 関節リウマチ / 細胞内代謝 / 遺伝子多型 / 薬理遺伝学 / 民族差 |
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| Outline of Final Research Achievements |
Methotrexate (MTX) is an essential drug for treatment of rheumatoid arthritis (RA). However, the response and tolerability to this drug is known to vary among patients and ethnics. In fact, MTX doses in clinical settings were approximately 7-9 mg/week and >15 mg/week in Japanese and Caucasian RA patients, respectively. We then focused to the intracellular polyglutamates (PGs) of MTX in patients with RA. Efficiency of PGs was lower in patients with MTX adverse events. Genotypes of folylpolyglutamate synthase (FPGS) significantly influenced to the concentration of MTXPGs, resulting in the increased efficiency of PGs in a Caucasian population when compared to our Japanese RA patients.
In conclusion, differences in allele frequencies of FPGS gene between different ethnic populations may suggest the significant differences in tolerable doses to MTX between these cohorts. (Appeared in Sci Rep. 6, 35615)
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| Free Research Field |
内科学、リウマチ学、臨床薬理学
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