Abstract
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 hGRα, 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. Results: In 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. Conclusion: This 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.
| Original language | English (US) |
|---|---|
| Article number | 16 |
| Journal | BMC Genetics |
| Volume | 20 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 8 2019 |
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Keywords
- Alternative splicing
- Deletions
- Glucocorticoid receptor
- Insertions
- Locus specific database
- Polymorphisms
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
Uncovering a multitude of human glucocorticoid receptor variants : An expansive survey of a single gene. / Leventhal, Stacey M.; Lim, Debora; Green, Tajia L.; Cantrell, Anna E.; Cho, Kiho; Greenhalgh, David G.
In: BMC Genetics, Vol. 20, No. 1, 16, 08.02.2019.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Uncovering a multitude of human glucocorticoid receptor variants
T2 - An expansive survey of a single gene
AU - Leventhal, Stacey M.
AU - Lim, Debora
AU - Green, Tajia L.
AU - Cantrell, Anna E.
AU - Cho, Kiho
AU - Greenhalgh, David G
PY - 2019/2/8
Y1 - 2019/2/8
N2 - 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 hGRα, 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. Results: In 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. Conclusion: This 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.
AB - 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 hGRα, 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. Results: In 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. Conclusion: This 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.
KW - Alternative splicing
KW - Deletions
KW - Glucocorticoid receptor
KW - Insertions
KW - Locus specific database
KW - Polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=85061236248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061236248&partnerID=8YFLogxK
U2 - 10.1186/s12863-019-0718-z
DO - 10.1186/s12863-019-0718-z
M3 - Review article
C2 - 30736733
AN - SCOPUS:85061236248
VL - 20
JO - BMC Genetics
JF - BMC Genetics
SN - 1471-2156
IS - 1
M1 - 16
ER -