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

Khair Rafiq1, Sanaullah Khan1, Muhammad Bar Khan1

  • 1Institute of Zoological Sciences, University of Peshawar, Khyber Pakhtunkhwa, Pakistan.

Viral Immunology
|February 27, 2026
PubMed

Insights

Genetic variations in interferon gamma (IFN-γ) and interferon gamma receptor-1 (IFN-γR1) genes are linked to hepatitis C virus (HCV) chronicity. The AA genotype of IFN-γ and TC genotype of IFN-γR1 increase susceptibility, while TT and CC genotypes may offer protection.

Area of Science:

  • Immunogenetics
  • Hepatology
  • Virology

Background:

  • Hepatitis C virus (HCV) infection poses a significant global health challenge, often leading to chronic liver disease.
  • Interferon gamma (IFN-γ) and its receptor-1 (IFN-γR1) genes are crucial in managing viral infections.
  • Understanding the genetic basis of HCV chronicity is vital for public health strategies.

Purpose of the Study:

  • To investigate the association between specific gene polymorphisms in IFN-γ and IFN-γR1 and the development of chronic Hepatitis C (CHC).
  • To determine if these genetic variations influence the progression of liver disease in CHC patients.

Main Methods:

  • Genotyping of 310 participants (150 CHC patients, 160 healthy controls) using PCR and Sanger sequencing.
  • Analysis focused on the intron-1 polymorphism of the IFN-γ gene and the promoter-56 polymorphism of the IFN-γR1 gene.
  • Statistical analysis to compare genotype frequencies between patient groups and controls.

Main Results:

  • The AA genotype of IFN-γ (+874) was significantly associated with chronic liver complications (p=0.017).
  • The TC genotype of IFN-γR1 (-56) showed a significant association with an increased risk of liver cirrhosis and hepatocellular carcinoma (HCC) in CHC patients (p=0.027).
  • Specific genotypes (IFN-γ AA and IFN-γR1 TC) were linked to increased susceptibility to HCV chronicity and disease progression.

Conclusions:

  • The AA genotype of IFN-γ and the TC genotype of IFN-γR1 are associated with higher susceptibility to HCV chronicity.
  • The TT genotype of IFN-γ and the CC genotype of IFN-γR1 may confer a protective effect against HCV chronicity.
  • These findings highlight the role of specific genetic polymorphisms in HCV pathogenesis and disease outcomes.
Abstract

Related Concept Videos

Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
18.8K
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
63
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.1K
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
53
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
42
Drug toxicity: Idiosyncratic Reactions01:16

Drug toxicity: Idiosyncratic Reactions

Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
64