GLCCI1 Variation Is Associated with Asthma Susceptibility and Inhaled Corticosteroid Response in a Chinese Han Population

Xun, Qiufen; Li, Xiaozhao; He, Rong; Lu, Rongli; Zhang, Shichuan; Hu, Xinyue; Feng, Juntao

doi:10.1016/j.arcmed.2016.04.005

Cited by 27 publications

(43 citation statements)

References 30 publications

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“…and rs37973 variant genotypes were found to be related to less improvement in the FEV1 after ICS treatment for 12 weeks in Chinese patients [19]. Similar results were replicated in another Chinese study [22].…”

Section: Discussionsupporting

confidence: 66%

Effects of STIP1 and GLCCI1 polymorphisms on the risk of childhood asthma and inhaled corticosteroid response in Chinese asthmatic children

Huang

Zheng

et al. 2020

Preprint

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Background: Asthma is a common chronic lung disease in children. We aimed to determine the associations between stress-induced phosphoprotein 1 (STIP1) and glucocorticoid-induced transcript 1 (GLCCI1) polymorphisms and susceptibility of childhood asthma and inhaled corticosteroid (ICS) response in children. Methods: A total of 263 Chinese Han asthmatic children were recruited from the Xiangya Hospital, Central South University. Pulmonary function tests were performed before the treatment and 3 months after the treatment. 150 non-asthmatic children were recruited. Each participant's DNA was extracted from the peripheral blood and Method of MassARRAY was used to genotype the single-nucleotide polymorphisms (SNPs). Results: STIP1 rs2236647 wild-type homozygote (CC) was associated with increased asthma risk of children (OR=1.858，95% CI：1.205-2.864), but not associated with the onset age of asthma and ICS response. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms were not associated with the risk of childhood asthma. However, rs37969 mutant genotypes (TT/GT) were significantly associated with increased risk of early onset asthma (OR=2.254, 95% CI: 1.068-4.757) and less improvement in PD20 (p = 0.028). We also found significant associations between rs37969, rs37972 and rs37973 mutant genotypes and less improvement in maximal midexpiratory flow (MMEF) after ICS treatment for 3 months (p=0.036, p=0.010 and p=0.003, respectively). Conclusions: STIP1 rs2236647 was associated with asthma risk of children. GLCCI1 rs37969 mutant genotypes were associated with increased asthma risk of early onset and less improvement in airway hyper-responsiveness. GLCCI1 rs37969, rs37972 and rs37973 polymorphisms might be associated with pulmonary function in childhood asthma patients after ICS treatment.

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Section: Discussionsupporting

confidence: 66%

Effects of STIP1 and GLCCI1 polymorphisms on the risk of childhood asthma and inhaled corticosteroid response in Chinese asthmatic children

Huang

Zheng

et al. 2020

Preprint

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“…The G allele of rs37973 might downregulate GLCCI1 expression and decrease patient corticoid sensitivity [ 10 ]. Since this report, further studies have confirmed the association between GLCCI1 gene polymorphisms and the glucocorticoid response [ 23 – 25 ], though the findings of other relevant studies were not consistent with those of the original findings [ 26 , 27 ]. In 2016, Hu C et al successfully repeated the finding in a Chinese adult population [ 25 ].…”

Section: Discussioncontrasting

confidence: 57%

“…Since this report, further studies have confirmed the association between GLCCI1 gene polymorphisms and the glucocorticoid response [ 23 – 25 ], though the findings of other relevant studies were not consistent with those of the original findings [ 26 , 27 ]. In 2016, Hu C et al successfully repeated the finding in a Chinese adult population [ 25 ]. However, these studies were mostly limited to a disease model of asthma, and the conclusion needs to be extended to other allergic diseases.…”

Section: Discussioncontrasting

confidence: 57%

“…Based on the hypothesis that the GLCCI1 variant influences the effects of endogenous hormones, the GG genotype of rs37973 is expected to be associated with worse symptoms at baseline. Hu C et al found that the rs37973 variant was associated with a higher baseline forced expiratory volume in 1 second (FEV1) in a Chinese population [ 25 ]. However, our study did not find any association between the rs37973 polymorphism and baseline clinical severity.…”

Section: Discussionmentioning

confidence: 99%

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Glucocorticoid-Induced Transcription Factor 1 (GLCCI1) Variant Impacts the Short-Term Response to Intranasal Corticosteroids in Chinese Han Patients with Seasonal Allergic Rhinitis

Dai

et al. 2018

Med Sci Monit

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BackgroundGenetic correlations with the response to intranasal corticosteroids (INCS) in seasonal allergic rhinitis (SAR) treatment are unknown. This study aimed to evaluate the role of gene polymorphisms in the response to INCS in Chinese Han patients with moderate to severe SAR.Material/MethodsIn this study, 286 Chinese Han patients with SAR were genotyped for 4 candidate genes: the glucocorticosteroid receptor (NR3C1) gene, glucocorticoid-induced transcription factor 1 (GLCCI1) gene, T-box 21 gene (TBX21), and ATP binding cassette subfamily B member 1 (ABCB1) gene. Patients were treated with INCS for 4 weeks. The total nasal symptom score (TNSS), total ocular symptom score (TOSS), and visual analogue scale (VAS) score were assessed at baseline and on week 4. The primary endpoint was the effective rate after 4 weeks of INCS therapy.ResultsIn addition to the known contributing factors, one genotype of GLCCI1, namely, rs37973, was significantly associated with the INCS response (OR=0.598, 95% confidence interval: 0.41 to 0.87, P=0.007). The effective rate of the GG group was lower than those of the AA and AG groups (AA vs. GG: 73.7% vs. 51.6%, P=0.007; AG vs. GG: 78.8% vs. 51.6%, P=0.000). In addition, the TNSS, TOSS, and VAS were higher for the patients in the GG group than for those in the AA and AG groups on week 4.ConclusionsThe GLCCI1 rs37973 variant is a risk factor for glucocorticoid resistance in Chinese patients with SAR who receive short-term INCS treatment.

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“…Recently a novel pharmacogenetic variation in the glucocorticoid-induced transcript 1 gene ( GLCCI1 ) has been studied intensively in asthma 7 8 9 10 11 , since Tantisira and colleagues revealed in 2011 that the functional rs37973 polymorphism, which was in complete linkage disequilibrium with rs37972, might substantially cause a decreased response to ICSs therapy in non-Hispanic white asthmatics 12 . Subsequently, Van den Berge et al .…”

mentioning

confidence: 99%

GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients

Lei

Gao

Chen³

et al. 2017

Sci Rep

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Inhaled corticosteroids (ICSs) are widely prescribed in chronic obstructive pulmonary disease (COPD). However, little is known about predictors of ICSs therapeutic response. To investigate whether the variation in glucocorticoid-induced transcript 1 (GLCCI1) rs37973 is associated with ICS efficacy. A total of 204 clinically stable COPD patients were recruited and administered to inhaled fluticasone propionate/salmeterol combination (500/50 ug, twice daily) for 24 weeks. We genotyped the functional rs37973 and mainly assessed its effects on changes in lung function. In vitro, neutrophils isolated from parts of patients were incubated with various concentrations of dexamethasone (0, 10−6 M and 10−4 M) in the presence or absence of cigarette smoke extract, apoptosis was then assessed by flow cytometry. Patients with the homozygous GG genotype (increases of 15.3 ± 33.2 mL) had significantly poorer improvement in FEV1 than those with the AA (92.7 ± 29.6 mL; p < 0.001) or AG (59.4 ± 26.9 mL; p < 0.001) genotypes after 24-week treatment. In vitro, dexamethasone had less inhibitory effect of neutrophil apoptosis on GG genotype, which further validated the presence of mutant allele ‘G’ might negatively affect glucocorticoid responsiveness irrespective of smoking status. The GG genotype of rs37973 may associated with decreased ICSs efficacy in Chinese COPD patients.

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GLCCI1 Variation Is Associated with Asthma Susceptibility and Inhaled Corticosteroid Response in a Chinese Han Population

Cited by 27 publications

References 30 publications

Effects of STIP1 and GLCCI1 polymorphisms on the risk of childhood asthma and inhaled corticosteroid response in Chinese asthmatic children

Effects of STIP1 and GLCCI1 polymorphisms on the risk of childhood asthma and inhaled corticosteroid response in Chinese asthmatic children

Glucocorticoid-Induced Transcription Factor 1 (GLCCI1) Variant Impacts the Short-Term Response to Intranasal Corticosteroids in Chinese Han Patients with Seasonal Allergic Rhinitis

GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients

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