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

Abstract

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.