The impacts of gene polymorphisms on methotrexate in Chinese psoriatic patients
The impacts of gene polymorphisms on methotrexate in Chinese psoriatic patients
复制标题
基因多态性对中国银屑病患者甲氨蝶呤的影响
DOI：
10.1111/jdv.16440
复制
发表时间：
2020-06-01
影响因子：
9.2
通讯作者：
Chen, X.
中科院分区：
文献类型：
--
作者：
Chen, M.;Chen, W.;Chen, X.
背景甲氨蝶呤（MTX）是我国银屑病的一线治疗药物。MTX的代谢过程包括各种蛋白质和基因。既往研究表明，基因多态性对MTX疗效有显著影响。目的本研究的目的是验证候选基因多态性对甲氨蝶呤（MTX）在中国银屑病患者中的疗效的影响。每例患者均接受MTX治疗，剂量为7.5-15 mg/周，至少8周。根据银屑病面积和严重程度指数评分下降是否超过75%（PASI 75），将患者分为应答者和非应答者。根据之前的报道，使用Sequenom平台为每位患者选择了16种单核苷酸多态性（SNP）并进行基因分型。结果259例患者中，男性182例，女性77例，有关节炎表型者63例，无关节炎表型者196例，年龄19 ~ 70岁（49.7 ± 13.6）岁。患者的基线PASI值为13.8 ± 8.5，MTX治疗后33.2%的患者达到PASI 75缓解。携带ATP结合盒亚家族B成员1基因（ABCB 1）rs 1045642 TT基因型的患者与更严重的银屑病皮损相关（P = 0.032）。此外，ABCB 1 rs 1045642 TT基因型在无应答者中更常见。（P = 0.017），尤其是中重度患者（P = 0.002）和无银屑病关节炎的患者（P = 0.026）结论我们首次证明ABCB 1 rs 1045642 TT基因型多态性是MTX治疗后患者临床症状恶化的预测因子。甲氨蝶呤治疗中国银屑病患者皮损的反应
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.