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Genetic polymorphism predicting Methotrexate efficacy in Chinese patients with psoriasis vulgaris
Authors:Ye hong Kuang  Yan Lu  Ke xiang Yan  Pan pan Liu  Wang qing Chen  Min xue Shen  Yi jing He  Li sha Wu  Qun Shi Qin  Xing chen Zhou  Jie Li  Juan Su  Cheng zhiLv  Wu Zhu  Xiang Chen
Affiliation:1. Department of Dermatology, XiangYa Hospital, Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, Hunan, China;2. Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China;3. Institute of medical science, Xiangya Hospital, Central South University, Changsha, Hunan, China;4. Clinical Centre for Psoriasis, Dalian Skin Diseases Hospital, Dalian, Liaoning, China
Abstract:

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.
Keywords:Methotrexate  Psoriasis  Efficacy  SNP  Whole exome sequencing  MassARRAY
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