Aberrant GSTP1 promoter methylation predicts poor prognosis of acute-on-chronic hepatitis B pre-liver failure

Qiao, Chenyang; Li, Feng; Teng, Yue; Zhao, Jing; Hu, Na; Yong-sheng, Fan; Wang, Kai

doi:10.1007/s10238-017-0466-1

Cited by 15 publications

(6 citation statements)

References 46 publications

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“…Studies on the methylation status of the promoter region of glutathione S‐transferase P1 (GSTP1) and the prognosis of patients with chronic‐onset acute hepatitis B liver failure found that the frequency of methylation of the promoter region of GSTP1 in patients with chronic hepatitis B (CHB) liver failure was significantly higher than CHB, and the messenger RNA level of GSTPI is significantly lower than that of CHB. Abnormal methylation of GSTP1 is likely to be a prognostic biomarker of chronic acute liver failure 28 . In addition, we observed a phenomenon.…”

Section: Discussionsupporting

confidence: 52%

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Interaction between the HIF‐1α gene rs1957757 polymorphism and CpG island methylation in the promoter region is associated with the risk of anti‐tuberculosis drug‐induced liver injury in humans: A case–control study

Chong

Zhu

Ren

et al. 2022

Clinical Pharmacy Therapeu

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What is known and objective: HIF-1α gene polymorphisms, including rs11549465, rs11549467, rs1957757 and rs10873142, cause liver cell damage or pulmonary disease. The aim of this study was to analyse the association between the polymorphisms of the loci of the HIF-1α gene and its CpG island methylation in the promoter region with the risk of anti-tuberculosis drug-induced liver injury (ADLI).Methods: 286 patients with tuberculosis (TB) and ADLI (case group) and 286 patients with TB but without liver injury (control group) were matched one-to-one, among the 1728 TB patients recruited from July 2019 to July 2020. Genotyping of the four loci of the HIF-1α gene was confirmed using PCR-RFLP technology. Methylation of the HIF-1α gene was measured using the MSP method. The comparison of risk factors, HIF-1α genotype and methylation status between the case group and the control group was all achieved through univariate and multivariate conditional logistic regression.Results and discussion: Univariate analysis showed that the frequency of rs1957757 mutation genotype and CpG island methylation was significantly higher in the case group than in the control group (P<0.001, all). In contrast, there was no statistical difference in the frequency of mutated genotypes at the other three loci between the two groups (p = 0.21, p = 0.12 and p = 0.55, respectively). Further, multivariate analysis showed that CpG islands were methylated, the mutation genotype of the rs1957757 locus was independently associated with the high risk of ADLI, and the adjusted OR (95%CI) reached 1.92 (1.32-2.63) and 2.01 (1.32-2.83), respectively. Furthermore, taking the rs1957757 locus wild genotype and CpG islands without methylation as the reference group, the mutation genotype and CpG island methylation increased the risk of ADLI, and the probability of ADLI could reach 4.73 times that of the reference group. What is new and Conclusion:This is the first demonstration of the association of HIF-1α gene polymorphism and CpG island methylation with ADLI risk stratification.

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Section: Discussionsupporting

confidence: 52%

“…Abnormal methylation of GSTP1 is likely to be a prognostic biomarker of chronic acute liver failure. 28 In addition, we observed a phenomenon. The regulation of the HIF-1α signalling pathway is not only reflected in liver diseases but also in cardiovascular and cerebrovascular diseases, such as ischaemic stroke.…”

Section: Discussionmentioning

confidence: 65%

Interaction between the HIF‐1α gene rs1957757 polymorphism and CpG island methylation in the promoter region is associated with the risk of anti‐tuberculosis drug‐induced liver injury in humans: A case–control study

Chong

Zhu

Ren

et al. 2022

Clinical Pharmacy Therapeu

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“…[15][16][17] Our previous studies showed that the glutathione-S-transferase P1 (GSTP1) gene was aberrant methylated in Pre-ACHBLF. [18] Whether the methylation of the UBE2Q1 promoter is altered during the development of pre-ACHBLF is still unclear.…”

Section: Observational Studymentioning

confidence: 99%

“…Abnormal DNA methylation expression was also indentified in peripheral blood mononuclear cells in patients with ACHBLF [15–17] . Our previous studies showed that the glutathione-S-transferase P1 ( GSTP1 ) gene was aberrant methylated in Pre-ACHBLF [18] . Whether the methylation of the UBE2Q1 promoter is altered during the development of pre-ACHBLF is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Aberrant methylation of UBE2Q1 promoter is associated with poor prognosis of acute-on-chronic hepatitis B pre-liver failure

Hu¹,

Xie

Liu³

et al. 2021

Medicine

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Acute-on-chronic hepatitis B liver failure (ACHBLF) is one severe liver disease with rapid progression and high mortality. Identification of specific markers for the prediction of ACHBLF has important clinical significance. We explored the feasibility of UBE2Q1 gene promoter methylation as an early prediction and prognosis biomarker of ACHBLF.UBE2Q1 promoter methylation frequency was detected in 60 patients with acute-on-chronic hepatitis B pre-liver failure (Pre-ACHBLF), 40 patients with chronic hepatitis B and 20 cases of healthy control (HC). The UBE2Q1 mRNA was detected by quantitative real-time polymerase chain reaction.The methylation frequency of the UBE2Q1 promoter in pre-ACHBLF patients was 38.33%, which was significantly lower than that in chronic hepatitis B patients (60.00%) and HCs (65.00%). The UBE2Q1 mRNA expression in pre-ACHBLF patients with UBE1Q1 non-methylation was significantly higher than that in patients with UBE1Q1 promoter methylation. Further analysis showed that hypomethylation of the UBE2Q1 promoter was positively correlated with total bilirubin and international normalized ratio levels in patients with pre-ACHBLF, but negatively correlated with PTA level. COX multivariate analysis showed that the model for end-stage liver disease score and UBE2Q1 promoter hypomethylation status were potential early warning factors that can predict the progression of pre-ACHBLF to ACHBLF. The sensitivity and specificity of UBE2Q1 promoter methylation status combined with the model for end-stage liver disease score for early diagnosis of ACHBLF were 92.9% and 75.0%, respectively. The area under the receiver-operating characteristic curve was 0.895.The hypomethylation of UBE2Q1 promoter is associated with severity of Pre-ACHBLF, which could serve as a potential prognostic biomarker for pre-ACHBLF.Abbreviations: ACHBLF = acute-on-chronic hepatitis B liver failure, ACLF = acute-on-chronic liver failure, AFP = alpha fetoprotein, ALB = albumin, ALT = alanine aminotransferase, AST = aspartate aminotransferase, AUC = area under the ROC curve, CHB = chronic hepatitis B, GSTP1 = glutathione-S-transferase P1, HBeAg = Hepatitis B e antigen, HBsAg = hepatitis B surface antigen, HC = healthy control, INR =international normalized ratio, MELD = model for end-stage liver disease, PBMCs = peripheral blood mononuclear cells, Pre-ACHBLF = acute-on-chronic hepatitis B pre-liver failure, pre-ACLF = acute-on-chronic pre-liver failure, PTA = prothrombin time activity, ROC curves = receiver-operating characteristic curves, TBIL = total bilirubin.

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“…However, uniform criteria for predicting ACLF occurrence are lacking and patients who are truly at the risk of ACLF are still ill-defined. There are currently several models to evaluate the severity and prognosis of patients with severe liver disease, including the Child-Turcotte-Pugh (CTP) scoring system, the model for end-stage liver disease (MELD), the sequential organ failure assessment score (SOFA), and other predictive models, but none of them have been universally accepted for predict accurate incidence of ACLF (13)(14)(15). First, majority scoring systems were originally applied for the evaluation of liver disease severity to predict the outcome of patients.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Novel Risk Prediction Model Using Recursive Feature Elimination Algorithm for Acute-on-Chronic Liver Failure in Chronic Hepatitis B Patients With Severe Acute Exacerbation

et al. 2021

Front. Med.

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Background: Patients with chronic hepatitis B (CHB) with severe acute exacerbation (SAE) are at a progression stage of acute-on-chronic liver failure (ACLF) but uniform models for predicting ACLF occurrence are lacking. We aimed to present a risk prediction model to early identify the patients at a high risk of ACLF and predict the survival of the patient.Methods: We selected the best variable combination using a novel recursive feature elimination algorithm to develop and validate a classification regression model and also an online application on a cloud server from the training cohort with a total of 342 patients with CHB with SAE and two external cohorts with a sample size of 96 and 65 patients, respectively.Findings: An excellent prediction model called the PATA model including four predictors, prothrombin time (PT), age, total bilirubin (Tbil), and alanine aminotransferase (ALT) could achieve an area under the receiver operating characteristic curve (AUC) of 0.959 (95% CI 0.941–0.977) in the development set, and AUC of 0.932 (95% CI 0.876–0.987) and 0.905 (95% CI 0.826–0.984) in the two external validation cohorts, respectively. The calibration curve for risk prediction probability of ACLF showed optimal agreement between prediction by PATA model and actual observation. After predictive stratification into different risk groups, the C-index of predictive 90-days mortality was 0.720 (0.675–0.765) for the PATA model, 0.549 (0.506–0.592) for the end-stage liver disease score model, and 0.648 (0.581–0.715) for Child–Turcotte–Pugh scoring system.Interpretation: The highlypredictive risk model and easy-to-use online application can accurately predict the risk of ACLF with a poor prognosis. They may facilitate risk communication and guidetherapeutic options.

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Aberrant GSTP1 promoter methylation predicts poor prognosis of acute-on-chronic hepatitis B pre-liver failure

Cited by 15 publications

References 46 publications

Interaction between the HIF‐1α gene rs1957757 polymorphism and CpG island methylation in the promoter region is associated with the risk of anti‐tuberculosis drug‐induced liver injury in humans: A case–control study

Interaction between the HIF‐1α gene rs1957757 polymorphism and CpG island methylation in the promoter region is associated with the risk of anti‐tuberculosis drug‐induced liver injury in humans: A case–control study

Aberrant methylation of UBE2Q1 promoter is associated with poor prognosis of acute-on-chronic hepatitis B pre-liver failure

Development and Validation of a Novel Risk Prediction Model Using Recursive Feature Elimination Algorithm for Acute-on-Chronic Liver Failure in Chronic Hepatitis B Patients With Severe Acute Exacerbation

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