Hypermethylation of the galectin-3 promoter is associated with poor prognosis of acute-on-chronic hepatitis B liver failure

Dig Liver Dis. 2017 Jun;49(6):664-671. doi: 10.1016/j.dld.2017.01.158. Epub 2017 Jan 22.

Abstract

Background and aims: The possible role of galectin-3 in acute-on-chronic hepatitis B liver failure (ACHBLF) remains unknown. This study aimed to determine the methylation status of the galectin-3 promoter in patients with ACHBLF and analyze its prognostic value.

Methods: The methylation status of the galectin-3 promoter in patients with ACHBLF, chronic hepatitis B (CHB) and healthy controls (HCs) was determined by methylation-specific polymerase chain reaction (MSP). The galectin-3 mRNA level in peripheral blood mononuclear cells (PBMCs) was detected using real-time polymerase chain reaction (RT-PCR).

Results: The methylation frequency of the galectin-3 promoter was significantly higher while galectin-3 mRNA was lower in ACHBLF than in CHB and HCs. Galectin-3 promoter methylation was negatively correlated with the mRNA level in ACHBLF. In addition, ACHBLF patients carrying the methylated promoter showed shorter survival time, higher 3-month mortality, and higher model for end-stage liver disease (MELD) score when compared to ACHBLF patients carrying the unmethylated promoter. Moreover, promoter methylation was a better predictor of 3-week mortality than the MELD score in ACHBLF patients.

Conclusion: Our results suggest that hypermethylation of the galectin-3 promoter might be an early biomarker for predicting disease severity and prognosis in patients with ACHBLF.

Keywords: Acute-on-chronic hepatitis B liver failure; DNA methylation; Galectin-3; Prognosis.

MeSH terms

  • Acute-On-Chronic Liver Failure / genetics*
  • Adult
  • Biomarkers / blood
  • Blood Proteins
  • Case-Control Studies
  • China
  • DNA Methylation
  • Female
  • Galectin 3 / genetics*
  • Galectins
  • Hepatitis B, Chronic / complications*
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Liver Function Tests
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Promoter Regions, Genetic*
  • RNA, Messenger / blood
  • Regression Analysis

Substances

  • Biomarkers
  • Blood Proteins
  • Galectin 3
  • Galectins
  • LGALS3 protein, human
  • RNA, Messenger