Enhanced Demethylation of Interferon-.GAMMA. Gene Promoter in Peripheral Blood Mononuclear Cells Is Associated with Acute-on-Chronic Hepatitis B Liver Failure

Fan, Xinghua; Zou, Zhiqiang; Long, Bo; Guo, Yan‐Mei; Wang, Sikui; Dexing, Jia; Xu, Ai-Ling; Li, Feng-Cai; Fan, Yu–Chen; Wang, Kai

doi:10.1620/tjem.224.13

Cited by 12 publications

(14 citation statements)

References 27 publications

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“…Previous studies have shown that the presence of the +874T and A alleles is associated with high and low IFN-c expression, respectively [16,34]. Furthermore, the plasma IFN-c concentration was found to be significantly decreased in patients with chronic hepatitis B relative to healthy controls [15,35]. Additionally, Chen et al found that the level of Th1-type cytokines (including IFN-c) was higher and that of Th2-type cytokines (IL-4, IL-6, and IL-10) was lower in responders than in nonresponders after HBV antiviral treatment [36].…”

Section: Discussionmentioning

confidence: 91%

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The interferon‐gamma (IFN‐γ) +874T allele reduces the risk of hepatitis B infection in an Asian population

Sun

Tang

2013

Journal of Viral Hepatitis

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Increasing evidence suggests that polymorphism of the interferon-gamma (IFN-γ) gene in the first intron at position +874 may be associated with chronic hepatitis B virus (HBV) infection and/or HBV clearance. However, the results of relevant studies have been inconsistent. To derive a more precise estimation of the association, we performed a meta-analysis. In total, 10 independent studies including 1661 chronic HBV-infected patients and 1142 controls were included in this meta-analysis. In studies following Hardy-Weinberg equilibrium (HWE), a significantly decreased risk of chronic HBV infection was associated with the IFN-γ + 874TT genotype in the overall population (TT vs AA: odds ratio (OR) = 0.714, 95% confidence interval (CI) = 0.526-0.969, P = 0.031) when compared with a spontaneously recovered population. Subgroup analysis by ethnicity revealed a similar association in Asian individuals (TT vs AA: OR = 0.706, 95% CI = 0.518-0.962, P = 0.028). Moreover, when compared with a healthy control group, the 874T allele was associated with a significant lower risk of chronic HBV infection in the overall populations (TA vs AA: OR = 0.439, 95% CI = 0.193-0.997, P = 0.049; TT + TA vs AA: OR = 0.475, 95% CI = 0.271-0.832, P = 0.009) and in Asian individuals (TA vs AA: OR = 0.862, 95% CI = 0.744-0.999, P = 0.048). In conclusion, the IFN-γ + 874TT genotype and 874T allele reduce the risk of chronic HBV infection in Asian individuals.

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Section: Discussionmentioning

confidence: 91%

“…Previous studies have shown that the presence of the +874T and A alleles is associated with high and low IFN‐γ expression, respectively . Furthermore, the plasma IFN‐γ concentration was found to be significantly decreased in patients with chronic hepatitis B relative to healthy controls . Additionally, Chen et al .…”

Section: Discussionmentioning

confidence: 91%

The interferon‐gamma (IFN‐γ) +874T allele reduces the risk of hepatitis B infection in an Asian population

Sun

Tang

2013

Journal of Viral Hepatitis

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“…In infectious diseases, a growing number of studies have shown that DNA methylation plays a critical role in regulating the differentiation of immune cells and the expression of cytokines (12)(13)(14)(15). The methylation level of several genes, like IL-4, IL-10, IFN-γ and TNF-α had great changes with infection of bacterial and virus (16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

The methylation state of VDR gene in pulmonary tuberculosis patients

Jiang¹,

Zhu²,

Liu³

et al. 2017

J. Thorac. Dis.

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Background: Our previous study suggested that the methylation of vitamin D receptor (VDR) gene affected its expression and the defense against tuberculosis (TB) infection in vitro. In this study, we further investigated the methylation level of VDR gene in pulmonary TB patients. Methods:The consecutive TB patients who were admitted into our department from January 2013 to January 2015 were recruited. The potential methylation sites analyzed in this study included 16 CpG sites.The amplification of bisulfite modified genomic DNA was ligated to pUC18-T vector and the positive clone of blue-white selection was sequenced to analyze the methylation state of VDR gene.Results: This study had samples of 27 TB patients and 30 healthy controls. TB patients were in the hypermethylation state compared to the healthy controls. The significant differences between TB patients and healthy controls were detected in 7 of these 16 CpG sites. The mRNA expression of AKT, GSK3β and FOXO1 decreased in TB patients compared to that of healthy controls. J Thorac Dis 2017;9(11):4353-4357 jtd.amegroups.com the transcriptional response to infection, even in nonproliferating cells (6). The pathogenic bacteria infected human dendritic cells (DCs) immediately caused the active demethylation at thousands of loci. Although more and more studies were reported, epigenetics of genes associated with TB susceptibility remain largely untapped field.Vitamin D receptor (VDR) is a ligand-dependent transcription factor which mediated the activation of 1,25(OH) 2 D 3 (7). It predominantly located in the nuclei of target cells. Upon the binding of vitamin D, VDR forms a heterodimer with retinoid x-receptor (RXR). VDR complex regulates the activity of target molecules through binding to the specific vitamin D response elements (VDRE). VDR gene is one of the key components in the host defense against TB (8,9). The polymorphism of VDR gene contributes to the risk of TB. Our previous study suggested that the methylation of VDR gene affected its expression and the defense against TB infection in vivo (10). In this study, we further investigated the methylation level of VDR gene in TB patients and analyzed the correlation between the methylation level of VDR gene and patient phenotype. Our data confirmed the correlation between methylation of VDR gene and the occurrence of TB. Methods Ethical approvalThe protocol was approved by the Institutional Review Board (IRB) of Shanghai Pulmonary Hospital (Tongji University) (No. 2014-016). All participants signed the written informed consent. Patients and specimen collectionThe consecutive TB patients who were admitted into our department from January 2013 to January 2015 were recruited. The diagnosis of TB was based on the "Diagnostic criteria for tuberculosis (WS288-2008)" which was made by National Health and Family Planning Commission of the PRC and the Xpert MTB/RIF test which was recommended by the World Health Organization. Patients with chronic obstructive pulmonary diseases, asthma, lung cancer, diabetes and hyper...

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“…IFN-␥ can be predominantly released by macrophages, NK cells and T cells, and fulfills anti-viral and proinflammatory functions [21]. Several groups have described the upregulation of IFN-␥ in virus-or chemicalassociated ALF [22,23] and in vivo administration of anti-IFN-␥ antiserum displayed a protective effect by markedly suppressing the circulating IFN-␥ and TNF-␣ [23].…”

Section: The Critical Roles Of Kcs In the Pathogenesis Of Alfmentioning

confidence: 99%