Establishing predictive models for NB-UVB treatment efficacy and safety in psoriasis through a genome-wide association study

Summary: Background: NB-UVB phototherapy is an effective, cost-efficient, and safe treatment for patients with plaque psoriasis. However, the predictors of NB-UVB treatment response remain limited. Objective: We aimed to detect relevant SNPs in order to establish predictive models for the efficacy and safety of NB-UVB phototherapy. Methods:<b> </b>A total of 252 patients with moderate-to-severe plaque psoriasis were enrolled in this study and underwent 12 weeks of NB-UVB phototherapy. Extracted DNA from whole blood samples was genotyped using Infinium Global Screening Array-24 v3.0 BeadChip. GWAS was performed to identify SNPs related to NB-UVB treatment response. Predictive models for the efficacy and safety of NB-UVB therapy, which involved SNPs along with clinical parameters, were developed utilizing logistic regression and further evaluated by ROC curve and calibration curve. Results: After 4 weeks of NB-UVB phototherapy, 40.8% of patients achieved PASI 50. Through GWAS, we discovered that <i>SLC7A13</i> rs35314286 TA allele and <i>DYNC1H1</i> rs941636 A allele were significantly correlated with better efficacy of 4-week NB-UVB treatment. After 12 weeks of treatment, 61.4% of patients achieved PASI 75. Seven <i>ATP2B2</i> SNPs and ten <i>PSMB7</i> SNPs significantly impacted 12-week PASI 75 achievement. During the treatment, 29.8% of patients experienced AEs. Two <i>KCNA2</i> SNPs, seven <i>THSD7B</i> SNPs and one <i>TENM4</i> SNP were considerably associated with the occurrence of AEs. Based on the clinical parameters and NB-UVB relevant SNPs, predictive models for the efficacy and safety of NB-UVB phototherapy were established, demonstrating excellent predictive capacities with AUC value being 0.81 for 4-week efficacy, 0.80 for 12-week efficacy, and 0.85 for AE development. Conclusion:<b> </b>Multiple gene SNPs were identified to be correlated with the efficacy and safety of NB-UVB phototherapy. Moreover, predictive models of NB-UVB treatment response were subsequently established. Our findings might contribute to the advancement of precision phototherapy in psoriasis. Yingyuan Yu¹, Bingjie Li¹, Xilin Zhang¹, Yuling Shi¹ 1. Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China. Translational Studies: Preclinical