Genetic polymorphism predicting Methotrexate efficacy in Chinese patients with psoriasis vulgaris

Background: Methotrexate is the first systemic therapeutics of psoriasis. It is reported that 40% of the patients achieved a PASI75 after 12 weeks with a small dose of methotrexate (15 mg / w) treatment. So far there is not any large-scale exome sequencing been used to predict the efficacy of methotrexate in the treatment of psoriasis vulgaris. Objective: To analyze the genetic polymorphism to predict methotrexate efficacy in Chinese patients with psoriasis vulgaris. Methods: In this study, we used the whole exon high-throughput sequencing technology to detect the DNA sequence of 22 psoriasis vulgaris patients (11 responders, 11 non-responders) treated with methotrexate and captured approximately 236 variants with statistically significant in the whole exon sequencing, then in accordance with statistical differences and clinical relevance, we further selected 36 SNPs and 14 SNPs that have been reported in articles associated with the response of methotrexate. We used MassARRAY method to verify the 50 SNPs in 100 psoriatic patients treated with methotrexate. Results: We found 3 SNPs, rs216195T > C in SMG6, rs1050301G > A in IMMT, rs2285421T > C in UPK1A which might associate with the drug response of methotrexate. Conclusion: We have searched 3 new SNPs that could predict the efficacy of methotrexate in psoriasis vulgaris to some extent, providing a theoretical basis for precision medicine of methotrexate in future. (C) 2018 Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology.