Interleukin-10 polymorphisms and susceptibility to ARV associated hepatotoxicity
HariOm Singh1, Dharmesh Samani1, Sumitra Nain2
1Department of Molecular Biology, National AIDS Research Institute Pune, 411026, India.
Interleukin-10 (IL-10) gene variations may influence the risk of liver damage in HIV patients taking antiretroviral therapy (ART). This study found no significant link between IL-10 polymorphisms and ART-induced hepatotoxicity susceptibility.
Area of Science:
- Immunogenetics
- Pharmacogenomics
- Hepatology
Background:
- Interleukin-10 (IL-10) is an anti-inflammatory cytokine that can inhibit HIV replication.
- IL-10 gene polymorphisms have been implicated in drug-induced hepatotoxicity.
- Understanding these genetic factors is crucial for managing HIV treatment.
Purpose of the Study:
- To investigate the association between IL-10 gene polymorphisms (-819C/T and -1082A/G) and the susceptibility to antiretroviral (ARV) drug-induced hepatotoxicity in HIV patients.
- To explore the influence of IL-10 genotypes on the severity of hepatotoxicity and disease progression in HIV-infected individuals.
Main Methods:
- Genotyping of IL-10 (-819C/T, -1082A/G) polymorphisms using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method.
- Analysis of 165 HIV patients (34 with hepatotoxicity, 131 without) and 155 healthy controls.
- Statistical analysis including odds ratios (OR) and logistic regression to assess associations.
Main Results:
- The IL-10-819TT genotype was associated with increased risk and severity of ARV-induced hepatotoxicity (OR=1.61).
- This genotype was overrepresented in HIV patients with hepatotoxicity compared to healthy controls (26.5% vs. 13.5%).
- IL-10-819CT genotype correlated with advanced HIV disease stage (OR=0.49) and increased hepatotoxicity risk with alcohol and efavirenz use (OR=4.00). Nevirapine use was linked to hepatotoxicity severity (OR=0.23).
Conclusions:
- While certain IL-10 genotypes and environmental factors (tobacco, alcohol, specific ARVs) showed associations with hepatotoxicity risk and severity, the overall association between IL-10 polymorphisms and susceptibility to ARV-induced hepatotoxicity was found to be insignificant.
- Further research may be needed to elucidate the complex interplay between IL-10 genetics, environmental factors, and ARV-induced liver injury in HIV patients.
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