Association between IFN-gamma+874 polymorphisms and the clinical outcomes of hepatitis B and/or hepatitis C virus infection.

Abstract

To explore the association between polymorphisms of interferon-gamma gene intron 1 at position +874 (IFN-gamma+874) gene and the susceptibility of HBV and/or HCV infection with different clinical outcomes. IFN-gamma+874 gene SNP were detected in 277 subjects including 79 chronic HBV/HCV coinfections, 69 individuals only with HBV infection, 55 individuals only with HCV infection and 74 controls, by sequence specific primers-PCR (SSP-PCR). Hepatocellular injury as suggested by alanine aminotransferase (ALT) was detected by Beckman LX-20. The status of viral particles in serum was determined by RT-nPCR. The possible association of the polymorphism of IFN-gamma+874 with the susceptibility of HBV and/or HCV infection and the outcome of these infections were analyzed. (1) IFN-gamma+874 AA frequency in individuals with chronic HBV, HCV, HBV/HCV coinfections were significant higher than that in controls (chi(2) = 16.15, P = 0.01);OR (95%CI) of IFN-gamma+874 AA in chronic infection with HBV, HCV, HBV/HCV coinfections appeared to be 2.70 (1.24 - 5.92), 3.22 (1.43 - 7.25) and 4.02 (1.88 - 8.55) compared with +874 TA. No significant differences were found among HBV, HCV, HBV/HCV coinfections (chi(2) = 1.97, P = 0.73). There were no significant association of IFN-gamma+874 A/T allele frequency with HBV and/or with HCV infection (chi(2) = 4.87, P = 0.18). (2) The clinical outcomes of mild chronic hepatitis (CH), moderate/severe CH and cirrhosis with HBV and/or HCV infection were associated with IFN-gamma+874 AA [chi(2) = 14.17, P = 0.03; OR = 3.09 (1.51 - 6.33), 3.85 (1.70 - 8.70), 3.14 (1.08 - 9.17)]. No significant relationships were found between IFN-gamma+874 A/T allele frequency and the clinical outcome of HBV/HCV infection (chi(2) = 6.07, P = 0.11). (3) There were no significant associations of IFN-gamma+874 genotype/allele frequency with HCV duplication (chi(2) = 2.36, P = 0.31). (4) There were no significant associations of IFN-gamma+874 genotype/allele frequency with abnormal ALT (chi(2) = 0.15, P = 0.93). These results suggested that polymorphisms in the IFN-gamma+874 had some influence on chronic HCV and/or HBV infection, and on the outcome of HCV and/or HBV infections. IFN-gamma+874 AA genotype and T allele were possible risk to chronic HBV and/or HCV infections and to the outcomes of HBV and/or HCV infection. However, IFN-gamma+874 TA genotype might serve as possible protective factors to them.