Promotor methylation: Does it affect response to therapy in chronic hepatitis C (G4) or fibrosis?

• Main Authors: Abdel-Rahman N. Zekri, M.Sc., Ph.D., Ahmed M. Raafat, Suzan Elmasry, Abeer A. Bahnassy, Yasmin Saad, Hamed A. Dabaon, Mohamed El-Kassas, Hend I. Shousha, Auhood A. Nassar, Mohamed Ale EL-Dosouky, Nehal Hussein
• Format: Article
• Language: English
• Published: Elsevier 2014-09-01
• Series: Annals of Hepatology
• Subjects: HCV; Antiviral response; Promoter methylation
• Online Access: http://www.sciencedirect.com/science/article/pii/S1665268119312517

Background and aim. DNA methylation plays a critical role in the control of important cellular processes. The present study assessed the impact of promoter methylation (PM) of some genes on the antiviral response to antiviral therapy and it’s relation to the presence of fibrosis in HCV-4 infected patients from Egypt.Material and methods. Clinical, laboratory and histopathological data of 53 HCV-4 infected patients who were subjected to combined antiviral therapy were collected; patients were classified according to their response to treatment and the fibrosis status. The methylation profiles of the studied groups were determined using the following genes: APC, P14ARF, P73, DAPK, RASSF1A, and O6MGMT in patients’ plasma.Results. O6MGMT and P73 showed the highest methylation frequencies (64.2 and 50.9%) while P14 showed the lowest frequency (34%). Sustained virological response (SVR) was 54.7%with no significant difference in clinico-pathological or laboratory features between the studied groups. PM of O6MGM was significantly higher in non-responders (p value 0.045) while DAPK showed high methylation levels in responders with no significance (p value: 0.09) andPM of RASSF1A was significantly related to mild fibrosis (p value: 0.019). No significant relations were reported between PM of any of the studied genes and patients’ features.Conclusion. PM of some Tumor Suppressor genes increases in chronic active HCV-4. However, only 06MGMT can be used as a predictor of antiviral response and RASSF1A as a marker of marked fibrosis in this small set of patients. An extended study, including more patients is required to validate the results of this preliminary study.