Distribution of IFNG and IFNGR1 Genotypes among HCV-Infected Pakistani Patients: A Case–Control Study

Abstract

Hepatitis C virus infection is a significant health concern that leads to serious liver-related complications such as liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The immunoregulatory cytokines, interferon gamma (INFG) and interferon gamma receptor-1 (IFNGR1), genes play vital role in viral infections outcomes.  The current study aimed to determine the genetic distribution of single nucleotide polymorphisms (SNP), in IFNG and IFNGR1 genes in HCV positive patients. A cross-sectional study was carried on total of 190 subjects, including 30 Sustained Virological Responder (SVR), 80 HCV positive patients and 80 healthy controls. The RNA and DNA were extracted; PCR was carried out for HCV detection and genotyping. The in-house PCR was used for amplification of Intron-1 and Promoter of INF-γ, and IFN-γR1, while sequencing was performed through Sanger’s method. The prevalence of TT, AT and AA genotypes of IFNG at +874 was (0.40), (0.33) and (0.27) in SVR, (0.20), (0.55) and (0.25) in HCV positive patients,  while (0.45), (0.39) and (0.15) in healthy control respectively (p < 0.001).The frequency of the AT genotype was high in HCV positive patients (0.55) while the TT was significantly high in SVR (0.40) and in healthy control (0.45) (p < 0.0001). The frequency of TT, TC, and CC genotypes of IFNGR1 gene at -56 was (0.27), (0.43), and (0.30) in SVR, (0.29), (0.48) and (0.24) in HCV positive patients, while (0.39), (0.20) and (0.40) in healthy individuals respectively (p = 0.008). The TC genotype was significantly high in SVR (0.43), and (0.48) in HCV positive patients while the CC was more prevalent in healthy control (0.41).  It is concluded that the AT and AA genotypes of the IFNG and the TC genotype of the IFNGR1 were more prevalent in HCV-positive patients, while the TT genotype of the IFNG and the CC genotype of the IFNGR1 were highly prevalent in SVR and in healthy individuals. This suggests that certain genetic variations may influence susceptibility to HCV infection and affect treatment outcomes.