Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2015; 21(27): 8382-8388
Published online Jul 21, 2015. doi: 10.3748/wjg.v21.i27.8382
Demethylation of tumor necrosis factor-α converting enzyme promoter associated with high hepatitis B e antigen level in chronic hepatitis B
Zhen-Li Wang, Shuai Gao, Xin-You Li, Feng-Kai Sun, Feng Li, Yu-Chen Fan, Kai Wang
Zhen-Li Wang, Shuai Gao, Xin-You Li, Feng-Kai Sun, Feng Li, Yu-Chen Fan, Kai Wang, Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Yu-Chen Fan, Kai Wang, Institute of Hepatology, Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Wang ZL and Gao S performed the majority of the experiments and wrote the manuscript; Li XY and Li F collected all the human material and revised the manuscript; Sun FK and Fan YC acquired the data and performed statistical analysis; Wang K designed and supervised the study and revised the manuscript.
Supported by Key Project of Chinese Ministry of Science and Technology, No. 2012ZX10002007 and No. 2013ZX10002001; National Natural Science Foundation of China, No. 81171579, No. 81201287 and No. 81371832; Science and Technology Development Plan of Shandong Province, China, No. 2014GSF118068.
Institutional review board statement: The study was reviewed and approved by the Research and Ethics Committee at Qilu Hospital of Shandong University, China.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no conflicts of interest related to this work.
Data sharing statement: Technical appendix, statistical code, and data set available from the corresponding author at wangdoc876@126.com. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kai Wang, MD, PhD, Department of Hepatology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan 250012, Shandong Province, China. wangdoc876@126.com
Telephone: +86-531-82169596 Fax: +86-531-86927544
Received: January 26, 2015
Peer-review started: January 27, 2015
First decision: March 10, 2015
Revised: March 19, 2015
Accepted: May 4, 2015
Article in press: May 4, 2015
Published online: July 21, 2015
Processing time: 176 Days and 17.9 Hours
Abstract

AIM: To evaluate tumor necrosis factor-α converting enzyme (TACE) methylation status in patients with chronic hepatitis B (CHB).

METHODS: Eighty patients with hepatitis B e antigen (HBeAg)-positive CHB, 80 with HBeAg-negative CHB, and 40 healthy controls (HCs) were randomly enrolled in this study. Genomic DNA was extracted from peripheral blood mononuclear cells and methylation status of TACE promoter was determined by methylation-specific polymerase chain reaction. The clinical and laboratory parameters were collected.

RESULTS: One hundred and thirty of 160 patients with CHB (81.25%) and 38 of 40 HCs (95%) displayed TACE promoter methylation. The difference was significant (χ2 = 4.501, P < 0.05). TACE promoter methylation frequency in HBeAg-positive CHB (58/80, 72.5%) was significantly lower than that in HBeAg-negative CHB (72/80, 90%; χ2 = 8.041, P < 0.01) and HCs (χ2 = 8.438, P < 0.01). However, no significant difference was observed in the methylation frequency between HBeAg-negative CHB and HCs (χ2 = 0.873, P > 0.05). In the HBeAg-positive group, TACE methylation frequency was significantly negatively correlated with HBeAg (r = -0.602, P < 0.01), alanine aminotransferase (r = -0.461, P < 0.01) and aspartate aminotransferase (r = -0.329, P < 0.01).

CONCLUSION: Patients with HBeAg-positive CHB have aberrant demethylation of the TACE promoter, which may potentially serve as a biomarker for HBeAg seroconversion.

Keywords: Tumor necrosis factor-α converting enzyme; Methylation; Chronic hepatitis B; Methylation-specific polymerase chain reaction; Biomarker

Core tip: We retrospectively recruited 80 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB), 80 with HBeAg-negative CHB, and 40 healthy controls. We evaluated tumor necrosis factor-α converting enzyme (TACE) promoter methylation status in peripheral blood mononuclear cells and analyzed the association between TACE methylation status and clinical features. Aberrant demethylation of the TACE promoter in HBeAg-positive CHB was associated with high HBeAg, alanine aminotransferase and aspartate aminotransferase levels. These findings imply that demethylation of the TACE promoter may potentially serve as a biomarker for HBeAg seroconversion.