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预测中国寻常型银屑病患者甲氨蝶呤疗效的遗传多态性。

Genetic polymorphism predicting Methotrexate efficacy in Chinese patients with psoriasis vulgaris.

机构信息

Department of Dermatology, XiangYa Hospital, Hunan Key Laboratory of Skin Cancer and Psoriasis, Central South University, Changsha, Hunan, China.

Department of Dermatology, Hua Shan Hospital, Fu dan University, Shanghai, China.

出版信息

J Dermatol Sci. 2019 Jan;93(1):8-13. doi: 10.1016/j.jdermsci.2018.06.009. Epub 2018 Jun 28.

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 (15mg / 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.

摘要

背景

甲氨蝶呤是银屑病的第一种全身治疗药物。据报道,40%的患者在接受小剂量甲氨蝶呤(15mg/w)治疗 12 周后达到 PASI75。迄今为止,尚未有任何大规模外显子组测序用于预测甲氨蝶呤治疗寻常型银屑病的疗效。

目的

分析遗传多态性以预测中国寻常型银屑病患者甲氨蝶呤的疗效。

方法

本研究采用全外显子高通量测序技术检测 22 例接受甲氨蝶呤治疗的寻常型银屑病患者(11 例应答者,11 例无应答者)的 DNA 序列,在外显子测序中捕获约 236 个具有统计学意义的变异,然后根据统计学差异和临床相关性,进一步选择 36 个 SNP 和 14 个已报道与甲氨蝶呤应答相关的文献中报道的 SNP。我们使用 MassARRAY 方法在 100 例接受甲氨蝶呤治疗的银屑病患者中验证了 50 个 SNP。

结果

我们发现 3 个 SNP,SMG6 中的 rs216195T>C、IMMT 中的 rs1050301G>A 和 UPK1A 中的 rs2285421T>C,可能与甲氨蝶呤的药物反应有关。

结论

我们已经发现了 3 个新的 SNP,它们可以在一定程度上预测甲氨蝶呤治疗银屑病的疗效,为未来甲氨蝶呤精准医学提供了理论依据。

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