Variations of the human glucocorticoid receptor gene (NR3C1): Pathological and in vitro mutations.and polymorphisms
Variations of the human glucocorticoid receptor gene (NR3C1): Pathological and in vitro mutations.and polymorphisms
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DOI：
10.1002/humu.10213
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发表时间：
2003-06-01
期刊：
影响因子：
3.9
通讯作者：
Cotton, RGH
中科院分区：
文献类型：
--
作者：
Bray, PJ;Cotton, RGH
糖皮质激素（GC）耐药性可发生在许多疾病中。它可以是全身性的（如家族性糖皮质激素抵抗）或局部性的（如哮喘）。在许多情况下，这种类固醇抗性的原因在于糖皮质激素受体基因（GR/NR3C1）的突变或多态性，该基因属于核受体大家族。许多gc抗性细胞系已经在体外分离出来，其中一些是在体内产生或可能在体内产生的。这些突变及其定义的突变，以及在质粒中工程和体外表达的突变，都包括在本综述中。它还列出了多态性和个体研究，其中关联，相关研究已经进行。NR3C1位于染色体5q31上，包含10个外显子，编码777个氨基酸的蛋白质。NR3C1有两种天然的同工异构体，grα（功能性）和grβ（无激素，结合能力）。据报道，与糖皮质激素抗性相关的NR3C1基因共有15个错义突变、3个无义突变、3个移码突变、1个剪接位点突变和2个备选剪接突变以及16个多态性。NR3C1的突变和多态性数据将很快在新创建的特定位点数据库中找到。(C) 2003 Wiley-Liss, Inc。
Glucocorticoid (GC) resistance can occur in a number of diseases. It can be either generalized (i.e., familial glucocorticoid resistance) or localized (i.e., asthma). In many cases, a reason for this resistance to steroids lies with mutations or polymorphisms present in the glucocorticoid receptor gene (GR/NR3C1) that belongs to a large family of nuclear receptors. A number of GC-resistant cell lines have been isolated in vitro, some of which arose or may have arisen in vivo. These and the mutations defined in them are included in this review as well as mutations engineered in plasmids and expressed in vitro. It also lists polymorphisms and the individual studies where association,related studies have been performed. NR3C1 is located on chromosome 5q31 and contains 10 exons that code for a 777 amino acid protein. There are two naturally occurring isoforms of the NR3C1, GRalpha (functional) and GRbeta (no hormone, binding ability). A total of 15 missense, three nonsense, three frameshift, one splice site, and two alternative spliced mutations have been reported in the NR3C1 gene associated with glucocorticoid resistance as well as 16 polymorphisms. Mutation and polymorphism data for NR3C1 will soon be found on the newly created locus-specific database. (C) 2003 Wiley-Liss, Inc.