Genetic polymorphisms in folate pathway enzymes as a possible marker for predicting the outcome of methotrexate therapy in Japanese patients with rheumatoid arthritis
Genetic polymorphisms in folate pathway enzymes as a possible marker for predicting the outcome of methotrexate therapy in Japanese patients with rheumatoid arthritis
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DOI：
10.1111/j.1365-2710.2009.01046.x
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发表时间：
2009-06-01
影响因子：
2
通讯作者：
Itoh, K.
中科院分区：
文献类型：
--
作者：
Hayashi, H.;Fujimaki, C.;Itoh, K.
小剂量甲氨蝶呤（MTX）治疗广泛应用于类风湿关节炎（RA）的治疗。尽管RA患者对MTX的反应差异很大，但导致这种差异的因素仍不清楚。我们旨在确定这些因素，特别强调MTX的药物遗传学。我们评估了可能的因素，包括叶酸代谢途径酶的遗传多态性，与C反应蛋白累积值的相关性，C反应蛋白是MTX抗炎疗效的指标，还原型叶酸载体基因（RFC）G80 A和γ-谷氨酰水解酶基因（GGH）C-401 T的多态性与RA的发生密切相关。（β = 2.1194，P = 0.0017），具有RFC 80 A和GGH-401 T等位基因的RA患者对MTX的反应低于具有RFC 80 A和无GGH-401 T等位基因的RA患者。401 T等位基因。因此，这些数据可能有助于指导RA患者的MTX治疗。
Low-dose methotrexate (MTX) therapy is widely used in the treatment of rheumatoid arthritis (RA). Though the difference in response to MTX between patients with RA is large, the factors that contribute to this variability remain unclear.We aimed to identify those factors with a particular emphasis on the pharmacogenetics of MTX.We evaluated the association of possible factors, including genetic polymorphisms of folate metabolic pathway enzymes, with the cumulative value of C-reactive protein, an index of MTX anti-inflammatory efficacy, in 87 Japanese patients with RA.Polymorphisms of the reduced folate carrier gene (RFC) G80A and of the gamma-glutamylhydrolase gene (GGH) C-401T were more closely associated (beta = 2.1194, P = 0.0017) than other polymorphisms, with the anti-inflammatory response to MTX.Patients with RA having RFC 80A and GGH-401T alleles were less responsive to MTX than those with RFC 80A and without GGH-401T alleles. Thus, this data may be useful for guiding treatment of RA patients with MTX.