Genome-Wide Analysis of core Promoter Region Cytosine-Phosphate-Guanine Islands Hypermethylation Profiles In Chronic Hepatitis B Virus Patients In South Africa
Journal Title: INNOVATIVE JOURNAL OF MEDICAL AND HEALTH SCIENCE - Year 2016, Vol 6, Issue 1
Abstract
Purpose: Hepatitis B virus (HBV) infection causes epigenetic changes through DNA hypermethylation. HBV integrates into the human genome thereby facilitating viral persistence. Infected hepatocytes express DNA methyltransferases that hypermethylate and inactivate integrated HBV genome inserts. This defence mechanism will methylate adjacent host DNA; this may result in the methylation of tumour suppressor genes and cell-cycle regulators leading to hepatocyte injury and malignancy. The aim of this study was to investigate for the presence of genome-wide promoter region cytosine-phosphate-guanine islands hypermethylation in HBV infected patients. Materials and methods: Affymetrix Human Promoter 1.0R microarray chip was used for microarray analysis of DNA obtained from liver tissue of 17 HBV-infected patients, 2 normal liver histopathology controls, 7 hepatocellular carcinoma (HCC), 2 from liver tissue surrounding HCC lesions and 4 from patients with autoimmune hepatitis. Microarray data was analysed using Partek Genomic Suite focusing on the core promoter region within 100bp from transcription start site. Partek Pathway was used for biological pathway analysis. The discovered hypermethylation patterns were validated using bisulfite DNA sequencing in an additional set of 59 samples. Results: HBV infected patients had significant hypermethylation compared to other study groups. Genes controlling hepatic inflammation, tissue regeneration and carcinogenesis were significantly affected (P<0.01). Age over 40 years, cirrhosis, hepatic inflammation and HBV e antigen status correlated with hypermethylation (P<0.01). On bisulfite DNA sequencing, Cyclin D3gene promoter was particularly highly methylated. This was associated with HBV e antigen positive status, high viral load and genotype D (P=0.01). Conclusions: HBV-induced epigenetic changes were widespread, affecting genes controlling cell growth, differentiation, proliferation and apoptosis. These changes may explain the development of hepatic inflammation, fibrosis and malignancy observed in patients with chronic HBV infection.
Authors and Affiliations
Mankgopo Magdeline Kgatle, Catherine Wendy Spearman, Mark Wayne, Raj Ramesar, Asgar Ali Kalla, Manish Kandpal, Perumal Vivekanandan,Henry Norman Hairwadzi
Keywords
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- EP ID EP319459
- DOI 10.15520/ijmhs.2016.vol6.iss1.101.
- Views 79
- Downloads 0
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