Association of interferon‐γ and interferon regulatory factor 1 polymorphisms with asthma in a family‐based association study in Taiwan

Wang, Tsu‐Nai; Chu, Yu-Te; Chen, W.-Y.; Feng, Weilou; Shih, Neng-Yang; Hsiang, Chien-Yun; Ko, Ying‐Chin

doi:10.1111/j.1365-2222.2006.02551.x

Cited by 16 publications

(15 citation statements)

References 36 publications

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“…In the Guangdong Pearl River Delta region, the results show that the CA repeat sequence was repeated 11-18 times (i.e., alleles CA 11 -CA 18 ), as determined by capillary electrophoresis. This was different from other reports wherein 12-18 repetitions were found among the Taiwanese population (Wang et al, 2006) and 10-18 times among Indians (Nagarkatti et al, 2002). In the present study, the genotypic frequency distributions of CA 12 + CA 12 + , CA 12 + CA 12 − and CA 12 − CA 12 − were compared with those in the asthmatic group and the control group and no correlation was found between the frequency and asthma susceptibility.…”

Section: Discussioncontrasting

confidence: 81%

“…In the present study, the genotypic frequency distributions of CA 12 + CA 12 + , CA 12 + CA 12 − and CA 12 − CA 12 − were compared with those in the asthmatic group and the control group and no correlation was found between the frequency and asthma susceptibility. This observation is consistent with the results by Kumar and Ghosh (2008), but is contradictory with the results obtained from the Taiwan population (Wang et al, 2006) and that in India (Nagarkatti et al, 2002) wherein the correlation between genotypic frequency and asthma was reported. The disagreement might be related to the differences in ethnicity, region, and research methods among the different studies.…”

Section: Discussionsupporting

confidence: 77%

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The association between IFN-γ and IL-4 genetic polymorphisms and childhood susceptibility to bronchial asthma

Huang

Zhong

2012

Gene

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Section: Discussioncontrasting

confidence: 81%

Section: Discussionsupporting

confidence: 77%

The association between IFN-γ and IL-4 genetic polymorphisms and childhood susceptibility to bronchial asthma

Huang

Zhong

2012

Gene

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“…IRF-1 is an early response gene involved in a diverse set of transcriptional regulatory processes (21,25). Interestingly, a strong association was found between IRF-1 polymorphism and childhood atopic asthma (46,47). Further, mortality associated with injection of a lethal dose of lipopolysaccharide was significantly reduced in IRF-1 knockout mice (48).…”

Section: Discussionmentioning

confidence: 99%

Cytokines Induce an Early Steroid Resistance in Airway Smooth Muscle Cells

Tliba¹,

Damera²,

Banerjee³

et al. 2008

Am J Respir Cell Mol Biol

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We have previously shown that long-term treatment of airway smooth muscle (ASM) cells with a combination of TNF-a and IFN-g impaired steroid anti-inflammatory action through the up-regulation of glucocorticoid receptor beta isoform (GRb) (Mol Pharmacol 2006;69:588-596). We here found that steroid actions could also be suppressed by short-term exposure of ASM cells to TNF-a and IFN-g (6 h) as shown by the abrogated glucocorticoid responsive element (GRE)-dependent gene transcription; surprisingly, neither GRa nuclear translocation nor GRb expression was affected by cytokine mixture. The earlier induction of CD38, a molecule recently involved in asthma, seen with TNF-a and IFN-g combination but not with cytokine alone, was also completely insensitive to steroid pretreatment. Chromatin-immunoprecipitation (IP) and siRNA strategies revealed not only increased binding of interferon regulatory factor 1 (IRF-1) transcription factor to CD38 promoter, but also its implication in regulating CD38 gene transcription. Interestingly, the capacity of fluticasone to completely inhibit TNF-a-induced IRF-1 expression, IRF-1 DNA binding, and transactivation activities was completely lost in cells exposed to TNF-a and IFN-g in combination. This early steroid dysfunction seen with cytokine combination could be reproduced by enhancing IRF-1 cellular levels using constitutively active IRF-1, which dose-dependently inhibited GRE-dependent gene transcription. Consistently, reducing IRF-1 cellular levels using siRNA approach significantly restored steroid transactivation activities. Collectively, our findings demonstrate for the first time that IRF-1 is a novel alternative GRb-independent mechanism mediating steroid dysfunction induced by pro-asthmatic cytokines, in part via the suppression of GRa activities.

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“…Among them, genetic variants in PLAU have been reported to associate with asthma and with airway hyperresponsiveness [27]. Further, multiple studies have indicated the role of IRF1 , interferon regulator factor 1, in asthma risk in several ethnicities [28–32]. As a proof of concept, our work followed up on IRF1 , however, all other genes could be further examined as peripheral gene expression changes markers for GC sensitivity.…”

Section: Discussionmentioning

confidence: 97%

Peripheral blood IRF1 expression as a marker for glucocorticoid sensitivity

Chapin

Lenkala

Mai

et al. 2015

Pharmacogenetics and Genomics

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Despite of the common usage of glucocorticoids (GCs), a significant portion of asthma patients exhibit GC insensitivity. This could be mediated by diverse mechanisms, including genomics. Recent work has suggested that measuring changes in gene expression may provide more predictive information about GC insensitivity than baseline gene expression alone, and that expression changes in peripheral blood may be reflective of that in the airway. Through gene expression omnibus (GEO) analysis, we identified IRF1 whose expression is affected by GC treatment in airway smooth muscle (ASM) cells, normal human bronchial epithelial (NHBE) cells, and lymphoblastoid cell lines (LCLs). Significant IRF1 down-regulation post GC exposure was confirmed in two cultured airway epithelial cell lines and primary NHBE cells (p<0.05). We observed large inter-individual variation for GC induced IRF1 expression changes among primary NHBE cells tested. Significant down-regulation of IRF1 was also observed in six randomly selected LCLs (p<0.05) with variable degree of down-regulation among different samples. In peripheral blood mononuclear cells (PBMCs) obtained from healthy volunteers, variable down-regulation of IRF1 by GC was also shown. NFKB1, a gene whose expression is known to be down-regulated by GC and the degree of down-regulation reflective of GC response, was used as a control in our study. IRF1 shows more consistent down-regulation across tissue types when compared to NFKB1. Our results suggest GC induced IRF1 gene expression changes in peripheral blood could be used as a marker to reflect GC response in the airway.

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Association of interferon‐γ and interferon regulatory factor 1 polymorphisms with asthma in a family‐based association study in Taiwan

Abstract: These findings provide strong evidence of which IFN-gamma CA repeat and IRF-1 GT repeat polymorphisms influence the risk of asthma for children in Taiwan.

Cited by 16 publications

References 36 publications

The association between IFN-γ and IL-4 genetic polymorphisms and childhood susceptibility to bronchial asthma

The association between IFN-γ and IL-4 genetic polymorphisms and childhood susceptibility to bronchial asthma

Cytokines Induce an Early Steroid Resistance in Airway Smooth Muscle Cells

Peripheral blood IRF1 expression as a marker for glucocorticoid sensitivity

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