Abstract
BackgroundHepatitis B virus (HBV) genotypes have a distinct geographical distribution and influence disease progression and treatment outcomes. The purpose of this study was to investigate the distribution of HBV genotypes in Europe, the impact of mutation of different genotypes on HBV gene abnormalities, the features of CpG islands in each genotype and their potential role in epigenetic regulation.ResultsOf 383 HBV isolates from European patients, HBV genotypes A-G were identified, with the most frequent being genotype D (51.96%) in 12 countries, followed by A (39.16%) in 7 countries, and then E (3.66%), G (2.87%), B (1.57%), F (0.52%) and C (0.26%). A higher rate of mutant isolates were identified in those with genotype D (46.7%) followed by G (45.5%), and mutations were associated with structural and functional abnormalities of HBV genes. Conventional CpG island I was observed in genotypes A, B, C, D and E. Conventional islands II and III were detected in all A-G genotypes. A novel CpG island IV was found in genotypes A, D and E, and island V was only observed in genotype F. The A-G genotypes lacked the novel CpG island VI. “Split” CpG island I in genotypes D and E and “split” island II in genotypes A, D, E, F and G were observed. Two mutant isolates from genotype D and one from E were found to lack both CpG islands I and III.ConclusionsHBV genotypes A-G were identified in European patients. Structural and functional abnormalities of HBV genes were caused by mutations leading to the association of genotypes D and G with increased severity of liver disease. The distribution, length and genetic traits of CpG islands were different between genotypes and their biological and clinical significances warrant further study, which will help us better understand the potential role of CpG islands in epigenetic regulation of the HBV genome.
Highlights
Hepatitis B virus (HBV) genotypes have a distinct geographical distribution and influence disease progression and treatment outcomes
Geographical distribution of HBV genotypes in Europe A total of 383 HBV isolates were identified as 7 datasets: genotype A (n = 150, 39.16%), B (n = 6, 1.57%), C (n = 1, 0.26%), D (n = 199, 51.96%), E (n = 14, 3.66%), F (n = 2, 0.52%) and G (n = 11, 2.87%)
In this study we found that two mutant isolates of genotype D (GQ477456 and AB674414) and one mutant isolate from genotype E (GU563552) lacked both islands I and III (Table 5)
Summary
Hepatitis B virus (HBV) genotypes have a distinct geographical distribution and influence disease progression and treatment outcomes. Hepatitis B virus (HBV) infection is a serious health problem worldwide. The World Health Organization (WHO) has estimated that around 240 million people globally are chronically infected with HBV, which cause between 500,000 and 700,000 deaths annually [1]. In much of the developing world, (sub-Saharan Africa, most of Asia, and the Pacific), 8% to 10% of people in the general population become chronically infected. HBV infection is less common in Western Europe, a recent investigation by the European Centre for Disease Prevention and Control showed an unexpected. Based on a minimum divergence of 8% of the complete genome sequences, HBV is classified as different genotypes consecutively identified as genotypes A–J [4,5,6]. Genotype G was detected in HBV carriers from Germany [8], Netherlands [9] and Georgia
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