Supplementary Material for: Genetic polymorphisms of rs9949644 in MAPK4 are associated with clinical response to methotrexate in patients with psoriasis

Background The study aimed to investigate the relationship of MAPK4 genetic variants with the efficacy of 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 (SNPs) 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 three groups. While after treatment, MAPK4 levels in the AG or GG group showed a significantly down-regulated trend. Conclusions 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.

背景：本研究旨在探讨丝裂原活化蛋白激酶4（MAPK4）基因变异与甲氨蝶呤（MTX）对银屑病患者的治疗疗效之间的关联。
方法：将接受甲氨蝶呤治疗的患者，以第12周时银屑病面积与严重性指数（PASI）较基线降低≥75%或<75%，分别归类为应答者与无应答者；对310例患者的14个MAPK4单核苷酸多态性（Single Nucleotide Polymorphism，SNPs）位点基因型进行检测分析，并采用Western印迹（western blot）法检测MAPK4蛋白的表达水平。
结果：在校正混杂因素后，仅rs9949644多态性位点与治疗疗效存在显著关联。携带rs9949644 AG或GG基因型的患者，相较AA基因型携带者，可获得更优的临床应答；rs9949644多态性位点与PASI改善率显著相关。MAPK4蛋白水平与银屑病严重程度呈正相关，且在银屑病患者中表达更高；三组基因型患者的MAPK4蛋白水平无显著差异，但接受治疗后，AG或GG基因型组患者的MAPK4蛋白水平呈现显著下调趋势。
结论：本研究证实MAPK4与甲氨蝶呤治疗疗效存在显著关联，提示MAPK4可能参与银屑病的疾病进程，并可作为治疗应答的预测标志物。