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Lack of Association between IFN-γ, CXCL10 and TGF-β1 Gene Polymorphisms and Liver Complication in HIV-infected Thais
Chareeporn Akekawatchai1,2, Khaimuk Changsri1,2, Apikhun Tunkor3
1Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand.
Insights
Genetic variations in IFN-γ, CXCL10, and TGF-β1 were not linked to liver complications in Thai HIV patients. Age and gender were risk factors, while higher CD4+ counts offered protection against liver fibrosis.
Area of Science:
- Immunogenetics
- Hepatology
- Infectious Diseases (HIV/AIDS)
Background:
- Chronic liver disease is a significant concern for individuals with HIV, often exacerbated by inflammatory cytokines like interferon-gamma (IFN-γ) and transforming growth factor-beta 1 (TGF-β1).
- Chemokine (C-X-C motif) ligand 10 (CXCL10) also plays a role in liver disease progression in HIV patients undergoing long-term antiretroviral therapy (ART).
Purpose of the Study:
- To investigate the association between specific single nucleotide polymorphisms (SNPs) in IFN-γ, CXCL10, and TGF-β1 genes and the occurrence of liver complications in HIV-infected Thai individuals.
- To evaluate the role of IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β1 -509C/T SNPs in liver disease progression within this population.
Main Methods:
- A cross-sectional study involving 200 HIV-infected Thai patients undergoing ART.
- Assessment of liver health included evaluation for transaminitis and significant liver fibrosis using the Fibrosis-4 (FIB-4) score.
- Genotyping for the selected SNPs was performed using polymerase chain reaction (PCR)-based methods.
Main Results:
- High prevalence rates of transaminitis (30.1%) and significant liver fibrosis (FIB-4 score > 1.45, 18.8%) were observed.
- No significant association was found between the studied SNPs (IFN-γ +874T/A, CXCL10 G-201A/C-1596T, TGF-β1 -509C/T) and the presence of transaminitis or significant liver fibrosis (p > 0.05).
- Logistic regression identified older age and male gender as risk factors for liver fibrosis, while a CD4+ cell count exceeding 350 cells/µL was a protective factor.
Conclusions:
- The investigated SNPs in IFN-γ, CXCL10, and TGF-β1 genes do not appear to be significantly associated with liver complications in HIV-infected Thai individuals, particularly those on ART.
- Clinical factors such as age, gender, and CD4+ cell count are more influential in the development of liver fibrosis in this patient group.
Objective:
Chronic liver disease has become a leading cause of illness and death in people living with HIV and the production of the cytokines IFN-γ and TGF-β1, and chemokine CXCL10 during chronic inflammation contributes to liver disease progression in HIV patients under long-term anti-retroviral therapy. This study aimed to examine association of IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β1 -509C/T single nucleotide polymorphisms (SNPs) with liver complications in the HIV-infected Thais.
Methods:
A cross-sectional study was conducted in 200 Thai HIV patients who were evaluated for transaminitis and significant liver fibrosis by fibrosis-4 score (FIB-4), and genotypes for IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β1 -509C/T SNPs using PCR-based methods.
Result:
There were high rates of transaminitis (30.1%) and significant liver fibrosis assessed by FIB-4 score > 1.45 (18.8%) in this group of patients, mostly under anti-retroviral therapy (73.0%). The genotypes and alleles of IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β1 -509C/T SNPs were not associated with either transaminitis or FIB-4 score > 1.45 (p > 005). Logistic regression analysis identified age and gender as risk factors, and CD4+ cell count higher than 350 cells/ul as a protective factor of liver fibrosis in this study group.
Conclusion:
The IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β11 -509C/T SNPs were not significantly associated with liver complication in HIV-infected Thais, mostly under ART.
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