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Published on: March 24, 2015
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.
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.
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.
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