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风湿性多肌痛和巨细胞动脉炎中糖皮质激素抵抗的遗传易感性及治疗结果

Genetic Predispositions of Glucocorticoid Resistance and Therapeutic Outcomes in Polymyalgia Rheumatica and Giant Cell Arteritis.

作者信息

Smutny Tomas, Barvik Ivan, Veleta Tomas, Pavek Petr, Soukup Tomas

机构信息

Department of Pharmacology and Toxicology, Centre for Drug Development, Faculty of Pharmacy in Hradec Kralove, Charles University, 500 05 Hradec Kralove, Czech Republic.

Institute of Physics, Faculty of Mathematics and Physics, Charles University, 121 16 Prague, Czech Republic.

出版信息

J Clin Med. 2019 Apr 27;8(5):582. doi: 10.3390/jcm8050582.

Abstract

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely related chronic inflammatory diseases. Glucocorticoids (GCs) are first-choice drugs for PMR and GCA, although some patients show poor responsiveness to the initial GC regimen or experience flares after GC tapering. To date, no valid biomarkers have been found to predict which patients are at most risk for developing GC resistance. In this review, we summarize PMR- and GCA-related gene polymorphisms and we associate these gene variants with GC resistance and therapeutic outcomes. A limited number of GC resistance associated-polymorphisms have been published so far, mostly related to allele. Other genes such , and , , and may play a role, although discrepancies are often found among different populations. We conclude that more studies are required to identify reliable biomarkers of GC resistance. Such biomarkers could help distinguish non-responders from responders to GC treatment, with concomitant consequences for therapeutic strategy.

摘要

风湿性多肌痛(PMR)和巨细胞动脉炎(GCA)是密切相关的慢性炎症性疾病。糖皮质激素(GCs)是PMR和GCA的首选药物,尽管一些患者对初始GC方案反应不佳或在GC减量后病情复发。迄今为止,尚未发现有效的生物标志物来预测哪些患者发生GC抵抗的风险最高。在本综述中,我们总结了与PMR和GCA相关的基因多态性,并将这些基因变异与GC抵抗和治疗结果相关联。到目前为止,已发表的与GC抵抗相关的多态性数量有限,大多与等位基因有关。其他基因如 、 以及 、 、 可能也起作用,尽管不同人群之间经常存在差异。我们得出结论,需要更多研究来确定GC抵抗的可靠生物标志物。此类生物标志物有助于区分GC治疗的无反应者和有反应者,从而对治疗策略产生相应影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1937/6572549/9546fd98a2ae/jcm-08-00582-g001.jpg

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