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Methodology for Accurate Detection of Mitochondrial DNA Methylation
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Methodology for Accurate Detection of Mitochondrial DNA Methylation

Published on: May 20, 2018

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DNMT1 modulation in chronic hepatitis B patients and hypothetic influence on mitochondrial DNA methylation status

Giordano Madeddu1, Silvia Ortu1, Giovanni Garrucciu2

  • 1Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.

Journal of Medical Virology
|December 7, 2016
PubMed

Insights

Nucleos(t)ide analogs (NAs) used for chronic Hepatitis B virus (HBV) infection may cause epigenetic changes. Prolonged NA therapy is linked to increased DNA methyltransferase 1 (DNMT1) expression and mitochondrial DNA hypermethylation in CHB patients.

Area of Science:

  • Hepatology
  • Epigenetics
  • Mitochondrial Biology

Background:

  • Chronic Hepatitis B virus (CHB) infection is managed with nucleos(t)ide analogs (NAs).
  • Widespread NA use is associated with mitochondrial dysfunction, a previously unrecognized anomaly.
  • This study investigates the potential for NAs to induce persistent epigenetic alterations during long-term CHB treatment.

Purpose of the Study:

  • To explore the hypothesis that NAs cause persistent epigenetic changes in CHB patients undergoing prolonged therapy.
  • To analyze methylation in mitochondrial DNA (mtDNA) and the expression of DNA methyltransferases 1 (DNMT1) in NA-treated versus untreated CHB patients.

Main Methods:

  • Peripheral blood mononuclear cells (PBMC) were collected from CHB patients receiving NAs (n=18) and untreated patients (n=20).
  • Epigenetic analysis involved Bisulphite sequencing PCR to detect methylated cytosine residues in the mtDNA control region (D-loop).
  • Quantitative relative Real-Time Polymerase Chain Reaction (PCR) was used to assess DNMT1 gene expression.

Main Results:

  • DNMT1 expression was significantly higher in NA-treated patients compared to untreated patients (P < 0.000001).
  • DNMT1 expression showed a significant positive correlation with NA therapy duration (Spearman Rho = 0.67; P < 0.05).
  • Bisulphite PCR sequencing revealed increased cytosine methylation in mtDNA from NA-treated patients compared to controls.

Conclusions:

  • Nucleos(t)ide analog therapy in CHB patients is associated with DNMT1 overexpression and increased mtDNA hypermethylation.
  • These epigenetic alterations may play a role in mitochondrial gene regulation during NA treatment.
  • Further research is warranted to elucidate the precise mechanisms and clinical implications of these findings.
Keywords:
antiviral therapyepigeneticmethylationmitochondrial DNAnucleo(t)side analogs

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