Promoter methylation status and expression of PPAR-γ gene are associated with prognosis of acute-on-chronic hepatitis B liver failure

作者：Zhao, Ze-Hua; Fan, Yu-Chen; Zhao, Qi; Dou, Cheng-Yun; Ji, Xiang-Fen; Zhao, Jing; Gao, Shuai; Li, Xin-You; Wang, Kai^*

来源：Clinical Epigenetics, 2015, 7: 115.

DOI：10.1186/s13148-015-0149-2

• DNA methylation
• Acute-on-chronic hepatitis B liver failure
• Peroxisome proliferator-activated receptor gamma
• Cytokines
• Prognosis

Background: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) 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-gamma 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-gamma in ACHBLF was analyzed. @@@ Results: We found that aberrant PPAR-gamma promoter methylation was attenuated in ACHBLF patients compared with CHB patients and was responsible for the elevated PPAR-gamma expression level, which was negatively correlated with total bilirubin and international normalized ratio. Plasma level of TNF-alpha and IL-6 in ACHBLF patients were higher than CHB patients and healthy controls and significantly reduced in unmethylated group. ACHBLF patients with PPAR-gamma promoter methylation had poorer outcomes than those without. Correspondingly, PPAR-gamma 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-gamma expression rebound occurred in ACHBLF compared with CHB and could improve prognosis of ACHBLF by negatively regulating cytokines.

• 出版日期2015-10-28
• 单位山东大学