Expression and gene polymorphisms of interleukin 28B and hepatitis B virus infection in a Chinese Han population.

ABSTRACT

BACKGROUND: Recent genome-wide association studies found that genetic polymorphisms near the IL28B gene is strongly associated with sustained viral response and spontaneous viral clearance in chronically infected hepatitis C patients. AIMS: We aimed to evaluate the effects of IL28B variations on hepatitis B virus (HBV) infection in a Chinese Han population and to explore the association between IL28B polymorphisms and susceptibility to infection, viral clearance, disease progression, viral load and liver inflammation. METHODS: We determined three IL28B single gene polymorphisms (rs12979860, rs12980275 and rs8099917) in 203 individuals with chronic HBV infection, 203 individuals with self-limited HBV infection and 203 individuals negative for all HBV seromarkers. Interleukin (IL)28B serum levels were evaluated in all subjects. Additionally, peripheral blood mononuclear cells from 42 chronically HBV-infected individuals were subjected to whole-genome expression studies. RESULTS: The association among genotype, allele and haplotype frequencies of IL28B with alanine aminotransferase levels and HBV DNA was established. However, no significant differences were observed in genotype or allele frequencies among chronically HBV-infected, self-limited and healthy subjects. The serum IL28B level was lower in patients with chronic HBV infection than in the self-limited HBV-infected or healthy subjects. The serum IL28B level was correlated with the subject's genotype. Gene expression micro-array analysis showed enhanced IL28B expression in patients with low HBV viral load. CONCLUSIONS: Variability at the IL28B locus is associated with HBV viral load and hepatic inflammation. Genetic variation of IL28B may prevent HBV progression by reducing viral load and liver inflammation, providing a valuable gene therapy tool.