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Published on: November 7, 2018
Association of an HLA-G 14-bp Insertion/Deletion polymorphism with high HBV replication in chronic hepatitis
A B Laaribi1,2, I Zidi1, N Hannachi2
1Laboratory Microorganisms and Active Biomolecules, Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Abstract:
Identification of an HLA-G 14-bp Insertion/Deletion (Ins/Del) polymorphism at the 3' untranslated region of HLA-G revealed its importance in HLA-G mRNA stability and HLA-G protein level variation. We evaluated the association between the HLA-G 14-bp Ins/Del polymorphism in patients with chronic Hepatitis B virus (HBV) infection in a case-control study. Genomic DNA was extracted from 263 patients with chronic HBV hepatitis and 246 control subjects and was examined for the HLA-G 14-bp Ins/Del polymorphism by PCR. The polymorphic variants were genotyped in chronic HBV seropositive cases stratified according to HBV DNA levels, fibrosis stages and in a control population. There was no statistical significant association between the 14-bp Ins/Del polymorphism and increased susceptibility to HBV infection neither for alleles (P = 0.09) nor for genotypes (P = 0.18). The stratification of HBV patients based on HBV DNA levels revealed an association between the 14-bp Ins/Del polymorphism and an enhanced HBV activity with high HBV DNA levels. In particular, the Ins allele was significantly associated with high HBV DNA levels (P = 0.0024, OR = 1.71, 95% CI 1.2-2.4). The genotype Ins/Ins was associated with a 2.5-fold (95% CI, 1.29-4.88) increased risk of susceptibility to high HBV replication compared with the Del/Del and Ins/Del genotypes. This susceptibility is linked to the presence of two Ins alleles. No association was observed between the 14-bp Ins/Del polymorphism and fibrosis stage of HBV infection. We observed an association between the 14-bp Ins/Del polymorphism and high HBV replication characterized by high HBV DNA levels in chronic HBV patients. These results suggest a potential prognostic value for disease outcome evaluation.
Insights
The Human Leukocyte Antigen-G (HLA-G) 14-bp Insertion/Deletion polymorphism is linked to higher Hepatitis B virus (HBV) DNA levels in chronic HBV infection. This genetic variation may help predict disease activity and outcomes in patients.
Area of Science:
- Immunogenetics
- Hepatology
- Molecular Biology
Background:
- The Human Leukocyte Antigen-G (HLA-G) plays a crucial role in immune regulation and is implicated in various infections.
- A known polymorphism in the 3' untranslated region of HLA-G, the 14-bp Insertion/Deletion (Ins/Del), affects mRNA stability and protein levels.
- Chronic Hepatitis B virus (HBV) infection is a significant global health concern with complex host-pathogen interactions.
Purpose of the Study:
- To investigate the association between the HLA-G 14-bp Ins/Del polymorphism and susceptibility to chronic HBV infection.
- To evaluate the relationship between this polymorphism and viral load, disease progression, and fibrosis in HBV-infected patients.
Main Methods:
- A case-control study was conducted involving 263 patients with chronic HBV infection and 246 healthy controls.
- Genomic DNA was extracted, and the HLA-G 14-bp Ins/Del polymorphism was genotyped using Polymerase Chain Reaction (PCR).
- Statistical analyses were performed to assess associations with HBV infection, viral DNA levels, and fibrosis stages.
Main Results:
- No significant association was found between the HLA-G 14-bp Ins/Del polymorphism and overall susceptibility to HBV infection.
- A significant association emerged between the Ins allele and higher HBV DNA levels (P = 0.0024, OR = 1.71).
- The Ins/Ins genotype conferred a 2.5-fold increased risk of high HBV replication compared to other genotypes, while no link to fibrosis stage was observed.
Conclusions:
- The HLA-G 14-bp Ins/Del polymorphism is not associated with susceptibility to chronic HBV infection.
- This polymorphism, particularly the Ins allele and Ins/Ins genotype, is significantly associated with enhanced HBV replication (high viral load).
- The findings suggest a potential prognostic value of the HLA-G 14-bp Ins/Del polymorphism for evaluating disease outcomes in chronic HBV patients.
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