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遗传因素对银屑病治疗反应的影响:个性化医学的新见解。

Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine.

机构信息

Department of Dermatology, Hospital Universitario Ramón y Cajal, IRYCIS, Colmenar Viejo km 9.100, 28034 Madrid, Spain.

Faculty of Medicine, Universidad Francisco de Vitoria, 28223 Madrid, Spain.

出版信息

Int J Mol Sci. 2023 Jun 7;24(12):9850. doi: 10.3390/ijms24129850.

Abstract

Psoriasis is a chronic inflammatory disease with an established genetic background. The HLA-Cw06 allele and different polymorphisms in genes involved in inflammatory responses and keratinocyte proliferation have been associated with the development of the disease. Despite the effectiveness and safety of psoriasis treatment, a significant percentage of patients still do not achieve adequate disease control. Pharmacogenetic and pharmacogenomic studies on how genetic variations affect drug efficacy and toxicity could provide important clues in this respect. This comprehensive review assessed the available evidence for the role that those different genetic variations may play in the response to psoriasis treatment. One hundred fourteen articles were included in this qualitative synthesis. gene polymorphisms may influence the response to topical vitamin D analogs and phototherapy. Variations affecting the ABC transporter seem to play a role in methotrexate and cyclosporine outcomes. Several single-nucleotide polymorphisms affecting different genes are involved with anti-TNF-α response modulation (, , , , , , , and among others) with conflicting results. HLA-Cw06 has been the most extensively studied allele, although it has only been robustly related to the response to ustekinumab. However, further research is needed to firmly establish the usefulness of these genetic biomarkers in clinical practice.

摘要

银屑病是一种慢性炎症性疾病,具有明确的遗传背景。HLA-Cw06 等位基因和参与炎症反应和角质形成细胞增殖的基因中的不同多态性与疾病的发展有关。尽管有针对银屑病的有效且安全的治疗方法,但仍有相当一部分患者无法获得足够的疾病控制。关于遗传变异如何影响药物疗效和毒性的药物遗传学和药物基因组学研究可能为此提供重要线索。本综述全面评估了这些不同遗传变异在银屑病治疗反应中的作用的现有证据。共有 114 篇文章纳入了本次定性综合分析。基因多态性可能影响局部维生素 D 类似物和光疗的反应。影响 ABC 转运体的变异似乎在甲氨蝶呤和环孢素的疗效中起作用。影响不同基因的几种单核苷酸多态性与抗 TNF-α 反应调节有关(、、、、、、、和 等),但结果存在冲突。HLA-Cw06 是研究最多的等位基因,但它仅与乌司奴单抗的反应密切相关。然而,需要进一步的研究来明确这些遗传生物标志物在临床实践中的有用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6721/10298473/2706e2f019b1/ijms-24-09850-g001.jpg

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