RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin

Authors

  • Nikola S. Kokanov Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0002-2380-2028
  • Milena M. Krajnović Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0001-5638-2042
  • Snežana P. Jovanović-Ćupić Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0002-3389-7278
  • Bojana R. Kožik Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0002-2983-4151
  • Nina M. Petrović Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0003-2503-1228
  • Ana M. Božović Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0002-6487-6365
  • Vesna Lj. Mandušić Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Mike Petrovića Alasa 12-14, Belgrade, Serbia https://orcid.org/0000-0002-2221-3707

DOI:

https://doi.org/10.2298/ABS211208004K

Keywords:

Hepatitis C virus, DNA methylation, RASSF1A, p16, biomarkers

Abstract

Paper description:

  • Patients with chronic hepatitis C genotype 1b would benefit from early detection of molecular markers predicting the response to therapy with pegylated interferon/ribavirin.
  • We investigated whether the methylation status of RASSF1A and p16 genes combined with host factors affects the response to therapy and disease progression.
  • Simultaneous presence of RASSF1A methylation and the IL28B CC genotype was significantly related to a sustained virologic response and methylation of the RASSF1A
  • The methylation status of RASSF1A and IL28B rs12979860 polymorphism could potentially help predict the response to therapy.

Abstract: Prevention of chronic hepatitis C (CHC) and its complications is based on antiviral therapy and early detection of reliable molecular markers in persons under risk. We investigated whether the methylation status of RASSF1A and p16 genes, alone or in combination with host and viral factors, affects the response to therapy with pegylated interferon/ribavirin (PEG-IFN/RBV). Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of the target promoter sequences of RASSF1A and p16 in circulating-free DNA from the peripheral blood of 49 patients with CHC genotype 1b. The methylation status of the examined genes did not affect the response to therapy. However, the simultaneous presence of either RASSF1A or p16 methylation and the CC genotype of IL28B was significantly related to a sustained virologic response (P=0.009 and P=0.032, respectively). After Bonferroni correction, only the result concerning the RASSF1A gene remained significant (P<0.0125). Methylation of RASSF1A was associated with the CC genotype of the IL28B gene (P=0.024) and a higher viral load (≥400 000 IU/mL, P=0.009). Our results suggest that combined analysis of RASSF1A gene methylation and IL28B rs12979860 polymorphism could potentially help in the prediction of therapy response in CHC genotype 1b patients.

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2022-04-01

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Kokanov NS, Krajnović MM, Jovanović-Ćupić SP, Kožik BR, Petrović NM, Božović AM, Mandušić VL. RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin. Arch Biol Sci [Internet]. 2022Apr.1 [cited 2024Nov.24];74(1):57-66. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/7311

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