Aberrant DNA methylation of G‐protein‐coupled bile acid receptor Gpbar1 predicts prognosis of acute‐on‐chronic hepatitis B liver failure. Issue 2 (4th July 2014)

• Record Type: Journal Article
• Authors: Gao, S.; Ji, X.‐F.; Li, F.; Sun, F.‐K.; Zhao, J.; Fan, Y.‐C.; Wang, K.
• Is Part Of: Journal of viral hepatitis. Volume 22:Issue 2(2015)
• Page Start: 110
• Page End: 117
• Publication Date: 2014-07-04
• Subjects: Hepatitis, Viral -- Periodicals; Hepatitis, Viral, Animal; Hepatitis, Viral, Human; 616.3623
• DOI: 10.1111/jvh.12277
• Languages: English
• ISSNs: 1352-0504

Abstract

<abstract abstract-type="main" id="jvh12277-abs-0001"> <title>Summary</title> <p>The G‐protein‐coupled bile acid receptor Gpbar1 <italic>(TGR5</italic>) has been demonstrated to be able to negatively regulate hepatic inflammatory response. In this study, we aimed to determine the methylation status of <italic>TGR5</italic> promoter in patients with acute‐on‐chronic hepatitis B liver failure (ACHBLF) and its predictive value for prognosis. We enrolled 76 consecutive ACHBLF patients, 80 chronic hepatitis B (CHB) patients and 30 healthy controls (HCs). Methylation status of <italic>TGR5</italic> promoter in peripheral mononuclear cell (PBMC) was detected by methylation‐specific polymerase chain reaction (MSP). The mRNA level of <italic>TGR5</italic> was determined by quantitative real‐time polymerase chain reaction (RT‐qPCR). We found that the frequency of <italic>TGR5</italic> promoter methylation was significantly higher in ACHBLF (35/76, 46.05%) than CHB patients (5/80, 6.25%; <italic>χ</italic><sup>2</sup> = 32.38, <italic>P</italic> < 0.01) and HCs (1/30, 3.33%; χ<sup>2</sup> = 17.50, <italic>P</italic> < 0.01). <italic>TGR5 </italic>mRNA level was significantly lower (<italic>Z</italic> = −9.12, <italic>P</italic> < 0.01) in participants with aberrant methylation than those without. <italic>TGR5</italic> methylation showed a sensitivity of 46.05% (35/76), specificity of 93.75% (75/80), positive predictive value (PPV) of 87.5% (35/40) and negative predictive value (NPV) of 64.66% (75/116) in discriminating ACHBLF from CHB patients. ACHBLF patients with methylated <italic>TGR5</italic> showed significantly poor survival than those without (<italic>P</italic> < 0.01). When used to predict 3‐month mortality of ACHBLF, <italic> TGR5</italic> methylation [area under the receiver operating characteristic curve (AUC) = 0.75] performed significantly better than model for end‐stage liver diseases (MELD) score (AUC = 0.65; <italic>P</italic> < 0.05). Therefore, our study demonstrated that aberrant TGR5 promoter methylation occurred in ACHBLF and might be a potential prognostic marker for the disease.</p> </abstract>