Impact of the genetic variants of <i>GLCCI1</i> on clinical features of asthmatic patients

Chiba, Shinji; Nakamura, Yutaka; Mizuno, Toshihiko; Abe, Kazuyuki; Horii, Yosuke; Nagashima, Hiromi; Sasaki, Nobuyuki; Kanno, Hiroyuki; Tanita, Tatsuo; Yamauchi, Kohei

doi:10.1111/crj.12647

Cited by 5 publications

(7 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(2, 5) Although these variants have fairly large effect sizes, in the case of GLCCI1 , GWAS indicated up to 6% of variation in response to ICS treatment,(4) but attempts at clinical validation have produced mixed results. (6–9) These findings suggests that additional genes may be important for determining ICS response in asthma. (10)…”

Section: Introductionmentioning

confidence: 94%

Systems biology and in vitro validation identifies family with sequence similarity 129 member A (FAM129A) as an asthma steroid response modulator

McGeachie

Clemmer

Hayete

et al. 2018

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 94%

Systems biology and in vitro validation identifies family with sequence similarity 129 member A (FAM129A) as an asthma steroid response modulator

McGeachie

Clemmer

Hayete

et al. 2018

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…Chiba et al reported that GLCCI1 was shown to be positively localized on bronchial epithelial cells and exhibit lower expression in asthma but higher expression with fluticasone stimulation ( 9 ). Therefore, Beas2B and A549 cells were used in this study to investigate the effect of GLCCI1 in epithelial cells.…”

Section: Resultsmentioning

confidence: 99%

“…Our own previous data showed that GLCCI1 variations are associated with asthma susceptibility and the ICS response in the adult Chinese Han population and that GLCCI1 expression might be affected by variations in GLCCI1 during the ICS response period ( 8 ). Additionally, GLCCI1 was positively localized on bronchial epithelial cells, and its variants could influence GC sensitivity ( 9 ). Therefore, GLCCI1 expressed on epithelial cells plays a crucial and important role in mediating the GC response in asthma, which might be beneficial for bio-identification, but the potential mechanism is not very clear.…”

Section: Introductionmentioning

confidence: 99%

GLCCI1 Deficiency Induces Glucocorticoid Resistance via the Competitive Binding of IRF1:GRIP1 and IRF3:GRIP1 in Asthma

Deng

Luo

et al. 2021

Front. Med.

View full text Add to dashboard Cite

GLCCI1 plays a significant role in modulating glucocorticoid (GC) sensitivity in asthma. This project determines the underlying mechanism that GLCCI1 deficiency attenuates GC sensitivity in dexamethasone (Dex)-treated Ovalbumin (OVA)-induced asthma mice and epithelial cells through upregulating binding of IRF1:GRIP1 and IRF3:GRIP1. Dexamethasone treatment led to less reduced inflammation, airway hyperresponsiveness, and activation of the components responsible for GC activity, as determined by decreased GR and glucocorticoid receptor interacting protein 1 (GRIP1) expression but augmented IRF1 and IRF3 expression in GLCCI1−/− asthmatic mice compared with wild type asthmatic mice. Moreover, the recruitment of GRIP1 to GR was downregulated, while the individual recruitment of GRIP1 to IRF1 and IRF3 was upregulated in GLCCI1−/− Dex-treated asthmatic mice compared to wild type Dex-treated asthmatic mice. We also found that GLCCI1 knockdown reduced GR and GRIP1 expression but increased IRF1 and IRF3 expression in Beas2B and A549 cells. Additionally, GLCCI1 silencing increased the interactions between GRIP1 with IRF1 and GRIP1 with IRF3, but decreased the recruitment of GRIP1 to GR. These studies support a critical but previously unrecognized effect of GLCCI1 expression on epithelial cells in asthma GC responses by which GLCCI1 deficiency reduces the GR and GRIP1 interaction but competitively enhances the recruitment of GRIP1 to IRF1 and IRF3.

show abstract

“…High-dose inhaled corticosteroid treatment increased the pulmonary function of patients homozygous for IL13 AA of rs20541 but not of patients homozygous for STAT4 TT of rs925847 [ 22 ]. Another analysis revealed an association between the homozygous GLCCI1 rs37972 and rs37973 and the asthmatic treatment steps used with the Japanese population, showing an OR of 2.78 and 2.28, respectively, but not with pulmonary function [ 23 ]. We concluded that the recent wide use of anti-IgE and tiotropium produced a clinically meaningful reduction in the exacerbation rate and a sequential improvement in pulmonary function.…”

Section: Discussionmentioning

confidence: 99%

Role of genetic variations of chitinase 3-like 1 in bronchial asthmatic patients

et al. 2018

Self Cite

View full text Add to dashboard Cite

BackgroundSingle nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1) are associated with bronchial severity and pulmonary function. CHI3L1 proteins are involved in both innate and adaptive immune responses; however, to date, the correlation of these SNPs and their age of onset of bronchial asthma has not been demonstrated.MethodsTo address the role of these genetic variations, 390 patients with well-controlled bronchial asthma and living in Japan were recruited, genotyped, and had a pulmonary function test performed on them in this study. To analyze the concentration levels of CHI3L1 protein, bronchial lavage fluids were examined.ResultsForced expiratory volume in one second, %predicted (%FEV1), was significantly decreased in homozygotes of rs1214194 compared to heterozygotes and wild type. The age of onset of adult bronchial asthma was significantly younger in GG homozygotes of rs4950928 and AA homozygotes of rs1214194 than in the other two genotypes. The concentration of CHI3L1 protein in bronchial lavage fluid increased in both homozygotes of rs4950928 and rs1214194.ConclusionsOur study demonstrated that the homozygotes of rs4950928 and rs1214194 of CHI3L1 might predict an early onset of bronchial asthma and have the propensity to promote airway remodeling.Trial registration JMA-IIA00045 remodeling-ICS

show abstract

Impact of the genetic variants of GLCCI1 on clinical features of asthmatic patients

Abstract: A worsening of pulmonary function caused by GLCCI1 variants could be prevented due to recently used medications based on new action mechanisms.

Cited by 5 publications

References 27 publications

Systems biology and in vitro validation identifies family with sequence similarity 129 member A (FAM129A) as an asthma steroid response modulator

Systems biology and in vitro validation identifies family with sequence similarity 129 member A (FAM129A) as an asthma steroid response modulator

GLCCI1 Deficiency Induces Glucocorticoid Resistance via the Competitive Binding of IRF1:GRIP1 and IRF3:GRIP1 in Asthma

Role of genetic variations of chitinase 3-like 1 in bronchial asthmatic patients

Contact Info

Product

Resources

About