title: Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease.
abstract: BACKGROUND
  Chronic liver injury can lead to the development of liver fibrosis and cirrhosis but only in a minority of patients. Currently, it is not clear which factors determine progression to fibrosis. We investigated whether DNA\methylation profile as determined by pyrosequencing can distinguish patients with mild from those with advanced/severe fibrosis in non-alcoholic liver disease (NAFLD) and alcoholic liver disease (ALD). To this end, paraffin-embedded liver biopsies were collected from patients with biopsy-proven NAFLD or ALD, as well as paraffin-embedded normal liver resections, genomic DNA isolated, bisulfite converted and pyrosequencing assays used to quantify DNA methylation at specific CpGs within PPARα, PPARα, TGFβ1, Collagen 1A1 and PDGFα genes. Furthermore, we assessed the impact of age, gender and anatomical location within the liver on patterns of DNA methylation in the same panel of genes.
  
  
  RESULTS
  DNA methylation at specific CpGs within genes known to affect fibrogenesis distinguishes between patients with mild from those with severe fibrosis in both NAFLD and ALD, although same CpGs are not equally represented in both etiologies. In normal liver, age, gender or anatomical location had no significant impact on DNA methylation patterns in the liver.
  
  
  CONCLUSIONS
  DNA methylation status at specific CpGs may be useful as part of a wider set of patient data for predicting progression to liver fibrosis.
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK.
authors: Müjdat
authors: M
authors: Zeybel
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK.
authors: Timothy
authors: T
authors: Hardy
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK.
authors: Stuart M
authors: SM
authors: Robinson
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK.
authors: Christopher
authors: C
authors: Fox
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK.
authors: Quentin M
authors: QM
authors: Anstee
authors: Cellular Pathology Department, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP UK.
authors: Thomas
authors: T
authors: Ness
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK.
authors: Steven
authors: S
authors: Masson
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK.
authors: John C
authors: JC
authors: Mathers
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK.
authors: Jeremy
authors: J
authors: French
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK.
authors: Steve
authors: S
authors: White
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH UK.
authors: Jelena
authors: J
authors: Mann
keywords: ALD; DNA methylation; Epigenetics; NAFLD; Pyrosequencing