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Background and Aim  Polymorphisms in some genes may influence the persistence of hepatitis C virus (HCV) infection, clinical outcome, HCV replication, and liver damage. This study was conducted to investigate the role of the interferon gamma (IFN‐γ) gene at (+874 T/A, −764 G/C, −179 C/A) single‐nucleotide polymorphisms (SNPs) and its receptor (IFN‐γR2) at (rs 2786067 A/C) SNP in the susceptibility of Egyptian families to HCV infection with high‐resolution techniques.    Methods  In total, 517 Egyptian families, with 2246 subjects, were recruited to this study from the Upper and Lower Egypt governorates and were classified into three groups: 1034 patients with chronic hepatitis C virus, 108 subjects with spontaneous virus clearance (SVC), and 1104 subjects as a healthy control group. All subjects were genotyped for (+874 T/A, rs2430561, −764 G/C, rs2069707, −179 C/A, rs2069709, and rs 27860067, A/C) SNPs of the IFN‐γ gene using the allelic discrimination real‐time polymerase chain reaction technique and were confirmed using sequence‐based typing.    Results  The carriage of T allele of (+874) IFN‐γ is a risky allele and was significantly higher in chronic hepatitis C more than other two groups (odds ratio [OR]: 2.6646,  P  < 0.0002). On the other hand, the C allele of (−764, rs2069707) is a protective allele and was higher in SVC than the other two groups (OR: 0.2709,  P  < 0.0001). However, both (−179 C/A, rs 2069709) and (rs 27860067, A/C) SNPs are not polymorphic enough to be studied in the Egyptian population.    Conclusions  HCV infection is associated with the T allele of (+874 rs2430561), while SVC of HCV is associated with the C allele of (−764, rs2069707) of the IFN‐γ gene.

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Association of interferon gamma gene polymorphism and susceptibility to hepatitis C virus infection in Egyptian patients: A multicenter, family‐based study