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与类风湿关节炎患者甲氨蝶呤相关的基因多态性及其对肝脏的不良影响。

, and polymorphisms and adverse liver effects of methotrexate in rheumatoid arthritis.

机构信息

Department of Medical Sciences, Rheumatology, Uppsala University, Sweden.

Department of Health Sciences, Luleå University of Technology, Luleå.

出版信息

Pharmacogenomics. 2020 Apr;21(5):337-346. doi: 10.2217/pgs-2019-0186. Epub 2020 Feb 6.

Abstract

To investigate whether variants of , and are associated with ALT elevation in rheumatoid arthritis patients starting methotrexate (MTX). Clinical and laboratory data were collected from the start of MTX treatment. Genotyping of , and was performed. Univariate and multiple logistic regression were used for statistical analysis. 34 out of 369 patients experienced ALT >1.5 × ULN less than 6 months from start. A1298C (rs1801131) was nominally associated with an ALT >1.5 × ULN within 6 months after the start of MTX (OR = 1.7 [95% CI: 1.04-2.9]; p = 0.03), but did not pass correction for multiple testing. A multiple model containing 1298C and clinical factors predicted the outcome (C-statistic 0.735). and were not associated with the outcome. A model containing 1298C and clinical factors might predict risk of early ALT elevation.

摘要

为了研究 、 和 中的变异是否与开始使用甲氨蝶呤 (MTX) 的类风湿关节炎患者的 ALT 升高有关。从 MTX 治疗开始时收集临床和实验室数据。对 、 和 进行基因分型。采用单变量和多变量逻辑回归进行统计分析。在开始 MTX 治疗不到 6 个月的 369 名患者中有 34 名出现 ALT>1.5×ULN。A1298C(rs1801131)在 MTX 开始后 6 个月内与 ALT>1.5×ULN 呈名义相关(OR=1.7[95%CI:1.04-2.9];p=0.03),但未通过多重检验校正。包含 1298C 和临床因素的多模型预测了结果(C 统计量 0.735)。和 与结果无关。包含 1298C 和临床因素的模型可能预测早期 ALT 升高的风险。

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