Association of IFN-γ and IFN-γ Receptor-1 Genes Polymorphisms with Hepatitis C Virus Infection Chronicity and Severity in Pakistani Patients.

BACKGROUND

Hepatitis C is a chronic liver disease caused by infection with the hepatitis C virus (HCV), representing a major concern for global public health. The interferon gamma and interferon gamma receptor-1 (IFN-γR1) genes play a significant role in viral infections. This study aims to investigate the association between polymorphisms in the IFN-γ and IFN-γR1 genes and the chronicity of HCV infection.

METHODOLOGY: This study included 310 participants, comprising 150 chronic Hepatitis C (CHC) patients and 160 healthy controls. Nucleic acids were isolated, and PCR was used for HCV detection. The intron-1 of IFN-γ and promoter-56 of IFN-γR1 genes were amplified through PCR and sequenced through Sanger's method.

RESULTS

The frequency of TT, AT, and AA genotypes of the IFN-γ at +874 in CHC patients was (20%), (57%), and (23%), while in healthy control, it was (46%), (38%), and (16%), respectively (p < 0.0001). In non-cirrhotic patients, they were (25.6%), (41.1%), and (33.3%); in cirrhotic patients, they were (26.3%), (39.5%), and (34.2%), while in HCC patients, they were (18.2%), (50%), and (31.8%). The AA genotype shows significant association with chronic liver complications (p = 0.017). The frequency of TT, TC, and CC genotypes of the IFN-γR1 gene at -56 was (21%), (43%), and (36%) in CHC patients, while in healthy individuals (38%), (21%), and (41%), (p < 0.0001). In non-cirrhotic patients, they were (30%), (49%), and (21%); in cirrhotic patients, they were (32%), (44%), and (24%), while in HCC patients, they were (22%), (46%), and (32%) (p = 0.027). The TC genotype is significantly associated with an increased risk of developing liver cirrhosis and HCC in CHC patients compared to healthy controls.

CONCLUSION

The current study shows that the AA genotype of the IFN-γ and TC genotype of the IFN-γR1 genes are associated with increased susceptibility and HCV chronicity. While the TT genotype of the IFN-γ and the CC genotype of the IFN-γR1 may confer a protective effect.