title: Alteration of methyl-CpG binding domain family in patients with chronic hepatitis B.
abstract: OBJECTIVE
  Epigenetics contributes to the outcome of chronic hepatitis B virus (HBV) infection. However, the role of methyl-CpG binding domain (MBD) family in the natural history of chronic hepatitis B (CHB) has not been demonstrated. It is aimed to investigate the dynamic expression of MBD family and assess the potential association of MBD family in the progression of CHB.
  
  
  METHODS
  Quantitative real-time polymerase chain reaction (RT-PCR) was used to determine the mRNA levels of MBD family in peripheral blood mononuclear cells (PBMCs) from 223 patients with CHB as training cohort, 146 patients with CHB as validation cohort [immune-tolerant (IT), immune clearance (IC), non/low-replicative (LR) and HBeAg negative hepatitis (ENH)], and 14 healthy controls (HCs).
  
  
  RESULTS
  The mRNA levels of MeCP2, MBD1, MBD2 and MBD4 were upregulated in patients with CHB compared with HCs. MBD1 mRNA was highest expressed in IT phase than other phases. The optimal cut-off value for MBD1 mRNA in discriminating IT phase from CHB was 0.0305 in both training and validation cohorts. Both MBD2 and MBD4 mRNA were highest expressed in IC phase than other phases. Moreover, the optimal cut-off values for MBD2 and MBD4 mRNA in discriminating IC phase from CHB were 0.0069 and 0.00099. Furthermore, MBD2 plus MBD4 performed better than MBD2 alone for discriminating IC phase from CHB in training (area under the curve of receiver operating characteristics [AUC] 0.736 vs. 0.671, P=0.0225) and validation cohorts (AUC 0.754 vs. 0.665, P=0.004). MeCP2 mRNA was highest expressed in patients with S3+S4. MeCP2 mRNA has higher AUC than APRI score for predicting S3+S4 and S4 in fibrosis.
  
  
  CONCLUSIONS
  MBD family is involved in the pathogenesis of CHB and is correlated with disease progression, suggesting the value in evaluating disease severity.
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China; Institute of Hepatology, Shandong University, Jinan 250012, China.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Fan
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China; Institute of Hepatology, Shandong University, Jinan 250012, China.
authors.forename: Long-Yan
authors.initials: LY
authors.lastname: Chen
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China; Institute of Hepatology, Shandong University, Jinan 250012, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China; Institute of Hepatology, Shandong University, Jinan 250012, China. Electronic address: wangdoc2010@163.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018450:Disease Progression; D044127:Epigenesis, Genetic; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger