title: Demethylation of tumor necrosis factor-α converting enzyme promoter associated with high hepatitis B e antigen level in chronic hepatitis B.
abstract: OBJECTIVE
  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 (χ (2) = 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%; χ (2) = 8.041, P < 0.01) and HCs (χ (2) = 8.438, P < 0.01). However, no significant difference was observed in the methylation frequency between HBeAg-negative CHB and HCs (χ (2) = 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).
  
  
  CONCLUSIONS
  Patients with HBeAg-positive CHB have aberrant demethylation of the TACE promoter, which may potentially serve as a biomarker for HBeAg seroconversion.
authors.affiliation: 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.
authors.forename: Zhen-Li
authors.initials: ZL
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Shuai
authors.initials: S
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Xin-You
authors.initials: XY
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Feng-Kai
authors.initials: FK
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Fan
authors.affiliation: 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.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000072198:ADAM17 Protein; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D019175:DNA Methylation; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D006513:Hepatitis B e Antigens; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: Biomarker; Chronic hepatitis B; Methylation; Methylation-specific polymerase chain reaction; Tumor necrosis factor-α converting enzyme