Communicated by Edward G.D. Tuddenham
Variations of the human glucocorticoid receptor gene (NR3C1): Pathological and in vitro mutations and polymorphisms†
Article first published online: 25 APR 2003
Copyright © 2003 Wiley-Liss, Inc.
Volume 21, Issue 6, pages 557–568, June 2003
How to Cite
Bray, P. J. and Cotton, R. G.H. (2003), Variations of the human glucocorticoid receptor gene (NR3C1): Pathological and in vitro mutations and polymorphisms. Hum. Mutat., 21: 557–568. doi: 10.1002/humu.10213
- Issue published online: 25 APR 2003
- Article first published online: 25 APR 2003
- Manuscript Accepted: 23 DEC 2002
- Manuscript Received: 1 AUG 2002
- glucocorticoid receptor;
- locus-specific database;
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, GRα (functional) and GRβ (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. Hum Mutat 21:557–568, 2003. © 2003 Wiley-Liss, Inc.