title: Promotor methylation: does it affect response to therapy in chronic hepatitis C (G4) or fibrosis?
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Abdel-Rahman
authors.initials: AR
authors.lastname: N Zekri
authors.affiliation: Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Raafat
authors.affiliation: Biochemistry Department, Faculty of Science, Cairo University, Cairo, Egypt.
authors.forename: Suzan
authors.initials: S
authors.lastname: Elmasry
authors.affiliation: Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Abeer A
authors.initials: AA
authors.lastname: Bahnassy
authors.affiliation: Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Saad
authors.affiliation: Organic Chemistry Department, Faculty of Science, Cairo University, Cairo, Egypt.
authors.forename: Hamed A
authors.initials: HA
authors.lastname: Dabaon
authors.affiliation: Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Kassas
authors.affiliation: Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Hend I
authors.initials: HI
authors.lastname: Shousha
authors.affiliation: Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Auhood A
authors.initials: AA
authors.lastname: Nassar
authors.affiliation: Biochemistry Department, Faculty of Science, Cairo University, Cairo, Egypt.
authors.forename: Mohamed Ale
authors.initials: MA
authors.lastname: El-Dosouky
authors.affiliation: Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Nehal
authors.initials: N
authors.lastname: Hussein
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004359:Drug Therapy, Combination; D004534:Egypt; D005260:Female; D005819:Genetic Markers; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D054884:Host-Pathogen Interactions; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011401:Promoter Regions, Genetic; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D005819:Genetic Markers; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes