Polymorphisms of interferon-inducible genes OAS associated with interferon-α treatment response in chronic HBV infection

• Published in: Antiviral research 2011-03, Vol.89 (3), p.232-237
• Main Authors: Ren, Shan, Yu, Haibin, Zhang, Hongwei, Liu, Ying, Huang, Yanxiang, Ma, Lina, Wei, Lai, Wu, Hao, Chen, Xinyue
• Format: Article
• Language: English
• Subjects: 2',5'-Oligoadenylate Synthetase - genetics; 2′,5′-Oligoadenylate synthetase(OAS); Age; alpha -Interferon; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Chronic infection; Gene Frequency; Gene polymorphism; Haplotype; Haplotypes; HBsAg seroconversion; Hepatitis B surface antigen; Hepatitis B virus; Hepatitis B virus (HBV); Hepatitis B, Chronic - drug therapy; Heterozygotes; Human viral diseases; Humans; Immunologic Factors - therapeutic use; Infectious diseases; Interferon; Interferon-alpha - therapeutic use; Interferon-α; Medical sciences; Pharmacology. Drug treatments; Polymorphism, Single Nucleotide; Seroconversion; Sex; Single nucleotide polymorphism (SNP); Single-nucleotide polymorphism; Treatment Outcome; Viral diseases; Viral hepatitis
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2011.01.006

To evaluate the role of host single nucleotide polymorphisms (SNPs) of 2′,5′-oligoadenylate synthetase (OAS) in predicting IFN response in patients with HBV infection, OAS gene and four SNPs were examined in 363 patients with chronic HBV infection (including 41 patients with HBsAg seroconversion) and 57 healthy controls. One SNP and three haplotypes were identified after adjustment for age, sex, HBV DNA. The frequency of OAS3T/C heterozygotes is 52.2% in responders (R) and 38.2% in non-responders (NR), with an odds ratio (OR) of 1.511 ( P = 0.018). For complete responders (CR) and NR, the OR reached 2.323( P = 0.023). Haplotype analyses revealed significant association between three OAS haplotypes and response to IFN-α treatment. Genotype combination and interaction between gene–gene analyses disclosed that there was a positive interaction between OAS2/OAS3 and OAS3/OASL, and the rate of OR was 2.46 (likelihood test, P = 0.004) and 4.46 (likelihood test, P = 0.004), respectively. Our results suggest that OAS gene variations may play an important role in response to IFN-α and provide a novel strategy for the resolution of HBV infection.