Do CCR5 (CCR5Δ32) and TLR3 (RS5743313) gene polymorphisms prevent chronic hepatitis B infection?
Burçin Tuncel1, Sedat Kaygusuz1, Derya Beyza Sayın Kocakap2
1Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Kırıkkale University, Kırıkkale, Türkiye.
Insights
Hepatitis B virus (HBV) genetic factors influence disease severity. Higher CCR5Δ32 allele frequency is linked to chronic hepatitis B, while increased interferon-gamma levels indicate HBV seroconversion.
Area of Science:
- Immunology
- Genetics
- Hepatology
Background:
- Hepatitis B virus (HBV) infection remains a global health concern.
- Individual genetic variations may significantly impact HBV susceptibility and disease progression.
- Immune response mediators like CCR5 and TLR3, along with interferon-gamma (IFN-ɣ), are crucial in managing HBV infection.
Purpose of the Study:
- To investigate the association between CCR5 (CCR5Δ32) and TLR3 (rs5743313) gene polymorphisms and serum IFN-ɣ levels in patients with HBV infection.
- To compare these factors in individuals who achieved natural HBV seroconversion versus those with chronic hepatitis B undergoing treatment.
- To identify potential genetic markers for HBV chronicity.
Main Methods:
- A case-control study comparing 100 patients with HBV seroconversion and 100 patients with chronic hepatitis B.
- Genotyping for CCR5Δ32 and TLR3 (rs5743313) polymorphisms.
- Quantification of serum IFN-ɣ levels using standard assays.
Main Results:
- The CCR5Δ32 polymorphism (Wt/Δ32 and Δ32/Δ32 genotypes) was found in significantly higher frequency in the chronic hepatitis B group (p=0.048).
- No significant association was observed for the TLR3 (rs5743313) gene polymorphism.
- Serum IFN-ɣ levels were markedly higher in the HBV seroconversion group (75 ± 89 ng/ml) compared to the chronic hepatitis B group (4.35 ± 17.27 ng/ml) (p < 0.001).
Conclusions:
- A higher frequency of the CCR5Δ32 allele may serve as a potential marker for progression to chronic hepatitis B.
- IFN-ɣ levels are significantly higher in individuals who have cleared HBV infection, suggesting a role in viral clearance.
- These findings highlight the interplay between host genetics and immune response in determining HBV infection outcomes.
Abstract:
Hepatitis B virus (HBV) is still a significant health problem in human. HBV severity or sensitivity of patients may be based on the individual genetic factors significantly. The aim of this study is to investigate the association of CCR5 (CCR5Δ32), TLR3 (rs5743313) functional gene polymorphisms, interferon-gamma (IFN-ɣ) level in HBV infection, which are thought to play an important role in innate and acquired immunity in patients who have undergone HBV seroconversion and those who have chronic hepatitis B disease and receive treatment. One hundred patients who are became naturally immune against HBV infection (HBsAg negative, anti-HBc IgG, and anti-HBs IgG positive), and 100 patients with chronic hepatitis B infection (>6 months HBsAg positive) who are receiving oral antiviral therapy were compared for CCR5Δ32, TLR3 (rs5743313) genotypes and serum IFN-ɣ level. It was found that CCR5Δ32 polymorphism (Wt/Δ32 and Δ32/Δ32) was significantly higher in the chronic hepatitis B group (p = 0.048) but not for TLR3 gene polymorphism. However, serum IFN-ɣ level was significantly higher in the HBV seroconversion group (75 ± 89 ng/ml) than in the chronic hepatitis B group (4.35 ± 17.27 ng/ml) (p < 0.001). In conclusion, a higher CCR5Δ32 allele frequency in patients with chronic hepatitis B might be considered as a marker of progression to chronic hepatitis.
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