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  • Title: Promoter methylation status and expression of PPAR-γ gene are associated with prognosis of acute-on-chronic hepatitis B liver failure.
    Author: Zhao ZH, Fan YC, Zhao Q, Dou CY, Ji XF, Zhao J, Gao S, Li XY, Wang K.
    Journal: Clin Epigenetics; 2015; 7():115. PubMed ID: 26516376.
    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.
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