Association of Interferon-gamma (IFN-g) Polymorphisms with Susceptibility of Hepatitis B Virus (HBV) Infection in the Hong Kong Chinese

Abstract

Background: Hepatitis B virus (HBV) infection is the most common cause of acute hepatitis and may progress to chronic liver disease, including cirrhosis or hepatocellular carcinoma (HCC). Host genetic factors are important for this progression. Interferon-gamma (IFN-γ) is a pro-inflammatory T-helper 1 (Th1) cytokine. It plays crucial roles in downregulation of HBV replication and its clearance.1 Serum IFN-γ levels were lower in the chronic hepatitis B patients than the normal controls, supporting that IFN-γ is involved in the progression of HBV infection.2 Objective: We aimed to determine whether a functional single nucleotide polymorphism (SNP) of IFN-γ may affect the susceptibility of HBV infection in Hong Kong Chinese population. Methods: We recruited 460 chronic HBV carriers and 87 individuals who had spontaneously recovered from HBV infection as evidenced by the presence of anti-HBs and anti-HBc antibodies. The SNP of IFN- γ at +874 A/T at intron 1 at the 5’ end of a CA repeat microsatellite sequence was detected using Genescan analysis. Results: For the spontaneous recovered individuals, the genotype frequencies were 54.0% for A/A, 39.1% for A/T and 6.9% for T/T. For the chronic HBV carriers, the genotype frequencies were 72.8% for A/A, 24.6% for A/T and 2.6% for T/T. The A/A genotype was predominant in the chronic carriers (odd ratio=4.09, CI=1.35-12.4), and its frequency was significantly higher than those with spontaneous recovery after adjusting for age and gender (p<0.0001). Conclusion: The polymorphism of IFN-γ gene at position +874 may confer susceptibility to persistent HBV infection. References: 1. Rehermann B et al. (2005) Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immun. 5: 215-27 2. Akpolat N et al. (2005) Relationship between serum cytokine levels and histopathological changes of liver in patients with hepatitis B. World J Gastroenterol. 11 (21):3260-3