Uncovering a multitude of human glucocorticoid receptor variants: an expansive survey of a single gene
Uncovering a multitude of human glucocorticoid receptor variants: an expansive survey of a single gene
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DOI：
10.1186/s12863-019-0718-z
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发表时间：
2019-02-08
期刊：
影响因子：
2.9
通讯作者：
Greenhalgh, David G.
中科院分区：
文献类型：
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作者：
Leventhal, Stacey M.;Lim, Debora;Greenhalgh, David G.
背景糖皮质激素因其强效抗炎作用而常用于临床;然而，已证实对治疗的反应存在显著差异。虽然潜在的机制尚未完全理解，这种可变的反应可能是人类糖皮质激素受体（hGR）表达和功能改变的结果。除了生物活性同种型hGR之外，对当前数据库和出版物的筛选揭示了迄今为止已报道的五种选择性剪接同种型和数百种变体。hGR编码基因NR 3C 1中的许多变化与病理生理学有关。然而，许多研究的重点是评估hGR的表达在体外或检测以前报道的variants.ResultsIn这项研究中，健康志愿者，烧伤和哮喘患者，以及从外周血单个核细胞分离的leukoreduced捐助者的全血，血液进行了筛选NR 3C 1亚型。我们确定了超过1500种变异，包括另外21种独特的剪接异构体，其中包含15个新的隐藏外显子。一个动态的数据库，命名为通用的人类生长激素受体（UHGR），创建注释和可视化的variants.ConclusionThis识别自然发生的和应力诱导的人类生长激素受体亚型，以及建立一个人类生长激素受体特异性数据库，可能会揭示新的模式或建议的兴趣领域，这将导致人类的应激反应系统的改善了解。
Background Glucocorticoids are commonly used in the clinical setting for their potent anti-inflammatory effects; however, significant variations in response to treatment have been demonstrated. Although the underlying mechanisms have yet to be fully understood, this variable response may be a result of alterations in human glucocorticoid receptor (hGR) expression and function. In addition to hGR, the biologically active isoform, a screening of current databases and publications revealed five alternative splice isoforms and hundreds of variants that have been reported to date. Many of these changes in the hGR-coding gene, NR3C1, have been linked to pathophysiology. However, many studies focus on evaluating hGR expression in vitro or detecting previously reported variants.ResultsIn this study, blood from healthy volunteers, burn and asthma patients, as well as from peripheral blood mononuclear cells isolated from leukoreduced donor whole blood, were screened for NR3C1 isoforms. We identified more than 1500 variants, including an additional 21 unique splice isoforms which contain 15 new cryptic exons. A dynamic database, named the Universal hGR (UhGR), was created to annotate and visualize the variants.ConclusionThis identification of naturally occurring and stress-induced hGR isoforms, as well as the establishment of an hGR-specific database, may reveal new patterns or suggest areas of interest that will lead to the improved understanding of the human stress response system.