Genetic Polymorphisms of rs9949644 in MAPK4 Are Associated with Clinical Response to Methotrexate in Patients with Psoriasis.

IF 3 3区医学 Q2 DERMATOLOGY

Dermatology Pub Date : 2024-01-01 Epub Date: 2023-07-26 DOI:10.1159/000533260

Zhijia Fan, Qiong Huang, Zhenghua Zhang, Ling Han, Xu Fang, Ke Yang, Guiqin Huang, Zhizhong Zheng, Nikhil Yawalkar, Yong Lin, Zhicheng Wang, Kexiang Yan

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引用次数: 0

Abstract

Background: The study aimed to investigate the relationship of MAPK4 genetic variants with the efficacy of methotrexate (MTX) in psoriasis patients.

Methods: Patients treated with MTX were classified as responders or nonresponders if the Psoriasis Area and Severity Index (PASI) at week 12 was reduced to greater than 75% or lower than 75%, respectively. The genotypes of 14 MAPK4 single-nucleotide polymorphisms in 310 patients were analyzed. The expression levels of MAPK4 protein were detected by Western blot.

Results: Only rs9949644 polymorphisms were associated with the efficacy after adjusting for the confounding factors. Patients with the rs9949644 AG or GG genotype had a better clinical response compared to patients with the AA genotype. Rs9949644 polymorphisms were significantly associated with the PASI improvement rate. Besides, the protein level of MAPK4, positively associated with the psoriasis severity, was higher in patients. There were no significant differences of MAPK4 protein levels among the three groups. While after treatment, MAPK4 levels in the AG or GG group showed a significantly down-regulated trend.

Conclusion: By demonstrating the significant association of MAPK4 with the efficacy of MTX, this study indicates that MAPK4 may be involved in the psoriasis progression and act as a predictor of therapeutic response.

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MAPK4中rs9949644的基因多态性与银屑病患者对甲氨蝶呤的临床反应有关。

背景：该研究旨在探讨MAPK4基因变异与银屑病患者甲氨蝶呤（MTX）疗效的关系：该研究旨在探讨MAPK4基因变异与甲氨蝶呤（MTX）对银屑病患者疗效的关系：方法：接受MTX治疗的患者在第12周时的银屑病面积和严重程度指数（PASI）降至大于75%或小于75%，则分别被归类为应答者或无应答者。研究分析了 310 名患者中 14 个 MAPK4 单核苷酸多态性的基因型。结果发现，只有 rs9949644 多态性基因的表达水平高于 MAPK4 蛋白的表达水平，而 rs9949644 多态性基因的表达水平低于 MAPK4 蛋白：结果：调整混杂因素后，只有rs9949644多态性与疗效相关。与 AA 基因型患者相比，rs9949644 AG 或 GG 基因型患者的临床反应更好。Rs9949644 多态性与 PASI 改善率显著相关。此外，患者体内与银屑病严重程度呈正相关的 MAPK4 蛋白水平较高。三组患者的 MAPK4 蛋白水平无明显差异。治疗后，AG 或 GG 组的 MAPK4 水平呈明显下调趋势：本研究表明，MAPK4与MTX的疗效有明显相关性，MAPK4可能参与了银屑病的进展，并可作为治疗反应的预测因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Dermatology 医学-皮肤病学

CiteScore

6.40

自引率

2.90%

发文量

审稿时长

1 months

期刊介绍： Published since 1893, ''Dermatology'' provides a worldwide survey of clinical and investigative dermatology. Original papers report clinical and laboratory findings. In order to inform readers of the implications of recent research, editorials and reviews prepared by invited, internationally recognized scientists are regularly featured. In addition to original papers, the journal publishes rapid communications, short communications, and letters to ''Dermatology''. ''Dermatology'' answers the complete information needs of practitioners concerned with progress in research related to skin, clinical dermatology and therapy. The journal enjoys a high scientific reputation with a continually increasing impact factor and an equally high circulation.