title: Promoter methylation status and expression of PPAR-γ gene are associated with prognosis of acute-on-chronic hepatitis B liver failure.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor gamma (PPAR-γ) has been demonstrated to be involved in anti-inflammatory reactions, but its role in acute-on-chronic hepatitis B liver failure (ACHBLF) is unclear. Therefore, DNA methylation patterns and expression level of PPAR-γ gene were detected in peripheral blood mononuclear cells (PBMCs) from 81 patients with ACHBLF, 50 patients with chronic hepatitis B (CHB), and 30 healthy controls, and the possible role of PPAR-γ in ACHBLF was analyzed.
  
  
  RESULTS
  We found that aberrant PPAR-γ promoter methylation was attenuated in ACHBLF patients compared with CHB patients and was responsible for the elevated PPAR-γ expression level, which was negatively correlated with total bilirubin and international normalized ratio. Plasma level of TNF-α and IL-6 in ACHBLF patients were higher than CHB patients and healthy controls and significantly reduced in unmethylated group. ACHBLF patients with PPAR-γ promoter methylation had poorer outcomes than those without. Correspondingly, PPAR-γ messenger RNA (mRNA) level was higher in survivors than non-survivors and gradually increased in survivors with time, while remained low level in non-survivors.
  
  
  CONCLUSIONS
  Aberrant promoter methylation decline and PPAR-γ expression rebound occurred in ACHBLF compared with CHB and could improve prognosis of ACHBLF by negatively regulating cytokines.
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China.
authors.forename: Ze-Hua
authors.initials: ZH
authors.lastname: Zhao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China ; Institute of Hepatology, Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Fan
authors.affiliation: Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan, 250012 China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China.
authors.forename: Cheng-Yun
authors.initials: CY
authors.lastname: Dou
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China.
authors.forename: Xiang-Fen
authors.initials: XF
authors.lastname: Ji
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China.
authors.forename: Xin-You
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China ; Institute of Hepatology, Shandong University, Wenhuaxi Road 107#, Jinan, 250012 China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
keywords: Acute-on-chronic hepatitis B liver failure; Cytokines; DNA methylation; Peroxisome proliferator-activated receptor gamma; Prognosis