Association between allelic variants of the human glucocorticoid receptor gene and autoimmune diseases: A systematic review and meta-analysis

Herrera, Cristian; Marcos, Miguel; Carbonell, Cristina; Mirón-Canelo, José Antonio; Espinosa, Gerard; Cervera, Ricard; Chamorro, Antonio-Javier

doi:10.1016/j.autrev.2017.11.034

Cited by 8 publications

(4 citation statements)

References 27 publications

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“…The human glucocorticoid receptor gene (NR3C1) has been reported to determine the differences and sensitivities of the glucocorticoid response in individuals with autoimmune diseases. 43,44 Based on this, changes in NR3C1 expression may affect the efficacy of glucocorticoid therapy in patients with ITP, which could explain the high NR3C1 expression observed in the remission group in our study. Moreover, the function of the glucocorticoid receptor was found to be regulated by the nuclear protein TPR, which is consistent with the co-upregulation of TPR and NR3C1 observed in our study.…”

Section: Discussionmentioning

confidence: 64%

Use of bioinformatic analyses in identifying characteristic genes and mechanisms active in the progression of idiopathic thrombocytopenic purpura in individuals with different phenotypes

Zhang

2020

J Int Med Res

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Objective To explore the mechanism underlying the progression of newly diagnosed idiopathic thrombocytopenic purpura (ITP) to its chronic or remission state using bioinformatic methods. Methods GSE56232 and GSE46922 gene expression profile datasets were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes were identified and characteristic genes were screened by weighted gene co-expression network analysis. These genes were used for function enrichment analysis and construction of a protein–protein interaction network. Finally, characteristic genes were verified to determine potential molecular mechanisms underlying ITP progression. Results We found that characteristic genes in the chronic ITP group were mainly involved in intracellular processes and ion binding, while characteristic genes in the remission ITP group were involved in intracellular processes and nuclear physiological activities. We identified a sub-network of characteristic genes, LMNA, JUN, PRKACG, SMC3, which may indicate the mechanism by which newly diagnosed ITP progresses to chronic. Although no meaningful signaling pathways were found, the expression of NR3C1, TPR, SMC4, PANBP2, CHD1, and U2SURP may affect ITP progression from newly diagnosed to remission. Conclusion Our findings improve the understanding of the pathogenesis and progression of ITP, and may provide new directions for the development of treatment strategies.

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Section: Discussionmentioning

confidence: 64%

Use of bioinformatic analyses in identifying characteristic genes and mechanisms active in the progression of idiopathic thrombocytopenic purpura in individuals with different phenotypes

Zhang

2020

J Int Med Res

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“…The rs6198 SNP has already been studied in many diseases, including autoimmune diseases, but there is a lack of data on GD. A systematic review and meta-analysis by Herrera C. et al [ 51 ] found a protective role for the minor G allele of rs41423247 in autoimmune diseases, especially among Caucasians (OR = 0.78; 95% CI: 0.65, 0.92; p = 0.004). However, the data were insufficient to support evidence that other SNPs, including rs6198, modulated the risk of autoimmune diseases [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…A systematic review and meta-analysis by Herrera C. et al [ 51 ] found a protective role for the minor G allele of rs41423247 in autoimmune diseases, especially among Caucasians (OR = 0.78; 95% CI: 0.65, 0.92; p = 0.004). However, the data were insufficient to support evidence that other SNPs, including rs6198, modulated the risk of autoimmune diseases [ 51 ]. Here, we demonstrated that rs6198 is a protective factor for GD.…”

Section: Discussionmentioning

confidence: 99%

NR3C1 rs6198 Variant May Be Involved in the Relationship of Graves’ Disease with Stressful Events

et al. 2023

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Although stressful events are known to trigger Graves’ disease (GD), the mechanisms involved in this process are not well understood. The NR3C1 gene, encoding for the glucocorticoid receptor (GR), presents single nucleotide polymorphisms (SNPs) that are associated with stress-related diseases. To investigate the relationship between NR3C1 SNPs, GD susceptibility, and clinical features, we studied 792 individuals, including 384 patients, among which 209 presented with Graves’ orbitopathy (GO), and 408 paired healthy controls. Stressful life events were evaluated in a subset of 59 patients and 66 controls using the IES-R self-report questionnaire. SNPs rs104893913, rs104893909, and rs104893911 appeared at low frequencies and presented similar profiles in patients and controls. However, variant forms of rs6198 were rarer in GD patients, suggesting a protective effect. Stressful events were more common in patients than controls, and were reported to have clearly occurred immediately before the onset of GD symptoms in 23 cases. However, no association was found between these events and rs6198 genotypes or GD/GO characteristics. We suggest that the NR3C1 rs6198 polymorphism may be an important protective factor against GD, but its relationship with stressful events needs further investigation.

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“…Similarly, a significantly higher frequency of G allele was described in patients with milder forms of Graves ophthalmopathy (GO) compared to patients with higher disease severity, suggesting that this SNP is associated with a lower risk of severe GO development [38]. A systematic review and meta-analysis evaluating the association between the rs41423247 SNP and autoimmune diseases, showed that the G allele might be even a protective factor for the development of systemic autoimmune disorders among Caucasian patients [39]. Therefore, the association of the G allele and a lower risk of autoimmunity or a milder disease phenotype is compliant with our results, showing that the C allele has a significantly higher frequency among MN patients than controls, which is in line with the autoimmunity in MN.…”

Section: Discussionmentioning

confidence: 99%

NR3C1 Glucocorticoid Receptor Gene Polymorphisms Are Associated with Membranous and IgA Nephropathies

Pac

Krata

Moszczuk

et al. 2021

Cells

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Glomerular diseases (GNs) are responsible for approximately 20% of chronic kidney diseases. Glucocorticoid receptor gene (NR3C1) single nucleotide polymorphisms (SNPs) are implicated in differences in predisposition to autoimmunity and steroid sensitivity. The aim of this study was to evaluate the frequency of the NR3C1 SNPs—rs6198, rs41423247 and rs17209237—in 72 IgA nephropathy (IgAN) and 38 membranous nephropathy (MN) patients compared to 175 healthy controls and to correlate the effectiveness of treatment in IgAN and MN groups defined as a reduction of proteinuria <1 g/24 h after 12 months of treatment. Real-time polymerase chain reactions and SNP array-based typing were used. We found significant rs41423247 association with MN (p = 0.026); a significant association of rs17209237 with eGFR reduction after follow-up period in all patients with GNs (p = 0.021) and with the degree of proteinuria after 1 year of therapy in all patients with a glomerulopathy (p = 0.013) and IgAN (p = 0.021); and in the same groups treated with steroids (p = 0.021; p = 0.012). We also observed the association between rs41423247 and IgAN histopathologic findings (p = 0.012). In conclusion, our results indicate that NR3C1 polymorphisms may influence treatment susceptibility and clinical outcome in IgAN and MN.

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Association between allelic variants of the human glucocorticoid receptor gene and autoimmune diseases: A systematic review and meta-analysis

Cited by 8 publications

References 27 publications

Use of bioinformatic analyses in identifying characteristic genes and mechanisms active in the progression of idiopathic thrombocytopenic purpura in individuals with different phenotypes

Use of bioinformatic analyses in identifying characteristic genes and mechanisms active in the progression of idiopathic thrombocytopenic purpura in individuals with different phenotypes

NR3C1 rs6198 Variant May Be Involved in the Relationship of Graves’ Disease with Stressful Events

NR3C1 Glucocorticoid Receptor Gene Polymorphisms Are Associated with Membranous and IgA Nephropathies

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