基因多态性对中国银屑病患者甲氨蝶呤的影响。

The impacts of gene polymorphisms on methotrexate in Chinese psoriatic patients.

作者信息

Chen M, Chen W, Liu P, Yan K, Lv C, Zhang M, Lu Y, Qin Q, Kuang Y, Zhu W, Chen X

机构信息

The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, Hunan, China.

出版信息

J Eur Acad Dermatol Venereol. 2020 Sep;34(9):2059-2065. doi: 10.1111/jdv.16440. Epub 2020 Jun 1.

DOI:10.1111/jdv.16440

PMID:32271961

Abstract

BACKGROUND

Methotrexate (MTX) is the first-line treatment for psoriasis in China. The metabolic processes of MTX include various proteins and genes. Previous studies have shown that gene polymorphisms had significant impacts on the efficacy of MTX. However, the influence of gene polymorphisms has not been reported in the Chinese psoriatic patients.

OBJECTIVE

The aim of this study was to verify the impacts of candidate genes polymorphisms on the effectiveness of MTX in a Chinese psoriatic population.

METHODS

In this study, we enrolled 259 psoriasis patients from two clinical centres. Each of them received MTX treatment at 7.5-15 mg/week for at least 8 weeks. Patients were stratified as responders and non-responders according to whether the Psoriasis Area and Severity Index score declined more than 75% (PASI75). According to previous reports, 16 single nucleotide polymorphisms (SNPs) were selected and genotyped for each patient using the Sequenom platform. Fisher's exact test, the chi-square test, Mann-Whitney tests and ANOVA analyses were used for statistical analysis.

RESULTS

Among 259 patients, there were 182 males and 77 females, 63 patients with psoriatic arthritis and 196 patients without arthritis phenotype, and the age of all patients ranged from 19 to 70 years (49.7 ± 13.6). The baseline PASI value of patients was 13.8 ± 8.5, and 33.2% of patients achieved a PASI75 response after MTX treatment. Patients carrying the ATP-binding cassette subfamily B member 1 gene (ABCB1) rs1045642 TT genotype were associated with more severe psoriasis skin lesion (P = 0.032). Furthermore, the ABCB1 rs1045642 TT genotype was found to be more frequent in non-responders (P = 0.017), especially in moderate-to-severe patients (P = 0.002) and patients without psoriatic arthritis (P = 0.026) after MTX treatment.

CONCLUSION

We have demonstrated for the first time that polymorphism of the ABCB1 rs1045642 TT genotype is predictive of a worse clinical response of skin lesions to MTX therapy in a Chinese psoriatic population.

摘要

背景

甲氨蝶呤（MTX）是中国银屑病的一线治疗药物。MTX的代谢过程涉及多种蛋白质和基因。既往研究表明，基因多态性对MTX的疗效有显著影响。然而，在中国银屑病患者中，基因多态性的影响尚未见报道。

目的

本研究旨在验证候选基因多态性对中国银屑病患者群体中MTX疗效的影响。

方法

本研究纳入了来自两个临床中心的259例银屑病患者。他们均接受MTX治疗，剂量为每周7.5 - 15mg，至少治疗8周。根据银屑病面积和严重程度指数（PASI）评分下降是否超过75%（PASI75），将患者分为反应者和无反应者。根据既往报道，选择16个单核苷酸多态性（SNP），并使用Sequenom平台对每位患者进行基因分型。采用Fisher精确检验、卡方检验、Mann-Whitney检验和方差分析进行统计分析。

结果

259例患者中，男性182例，女性77例，银屑病关节炎患者63例，无关节炎表型患者196例，所有患者年龄在19至70岁之间（49.7±13.6）。患者的基线PASI值为13.8±8.5，33.2%的患者在MTX治疗后达到PASI75反应。携带ATP结合盒亚家族B成员1基因（ABCB1）rs1045642 TT基因型的患者银屑病皮肤病变更严重（P = 0.032）。此外，发现ABCB1 rs1045642 TT基因型在无反应者中更常见（P = 0.017），尤其是在中重度患者（P = 0.002）和MTX治疗后无银屑病关节炎的患者（P = 0.026）中。