Association Of Interferon-γ Gene Haplotype In The Chinese Population With Hepatitis B Virus Infection

[Background] In general, cytokines encoded by different genes of human genome might strongly influence host cell-mediated immune responses, which play an important role in the clearance of virus by the infected host. And interferon-gamma (IFN-γ) produced by T lymphocytes and natural killer (NK) cells plays an essential role in affecting cellular immune responses. Functional study demonstrated that two single nucleotide polymorphisms (SNPs) located in the IFN-γ gene intron (at positions +874 and +2109) were involved in its transcriptional regulation.[ Objectives ] The aim of this study was to evaluate whether IFN-γ gene polymorphisms or its haplotypes might be associated with predisposition to HBV infection in the Chinese population.[Methods] The study included 181 cases with HBV infection and 272 sex, age-matched healthy controls. All genotyping were identified by polymerase chain reaction in association with the amplification refractory mutation system (ARMS-PCR) methodology. We used the software PHASE 1.0 to construct the haplotype of every individual. The unconditional logistic regression model was used to analyze the statistical association of genotypes or haplotypes in two groups adjusted by gender, age, smoking, drinking.[Results] A significant difference was observed between case and control groups. The frequency of +874A allele was significantly higher in patients than in controls (OR=2.25, 95%CI= 1.69-2.99, F<0.0001). However, no significant difference was found in the allelic frequencies of IFN-γ +2109A/G between cases and controls (P>0.05). By haplotype analysis, the frequency of haplotype AG(+874A and +2109G) revealed a significant difference in the cases in comparison to controls (P<0.0001). Multiple logistic regression analysis showed individuals possessing haplotype AG had an increased likelihood of HBV infection (OR=8.14, 95%CI=4.98-13.30). [Conclusions] IFN-γ +874A allele was associated with susceptibility to HBV infection. The risk of HBV infection in participants with a +874A allele was 2.25-fold higher compared to those with the T wild allele. Furthermore compared with other haplotypes, the risk of HBV infection in participants with the haplotype AG was 8.14-fold higher compared to those without the haplotype AG Our results suggest that haplotype AG containing +874A and +2109G may be a crucial risk factor of genetic susceptibility to HBV infection in the Chinese population.