BMC infectious diseases · 2026
Cytokine gene polymorphisms and susceptibility to chronic hepatitis B virus infection in familial clusters from Iran: a cross-sectional study.
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Aghcheli Bahman, Behboudi Emad, Naderi Malihe, Hosseini Seyed Masoud, Tatari Mahin, Shahramian Iraj, Khoshnia Masoud, Besharat Sima, Bakhtiari Mehran, Moradi Abdolvahab
Аннотация
BACKGROUND: This study investigated the associations between specific polymorphisms in the Interleukin-10 (IL-10), Interleukin-18 (IL-18), Interleukin-1 beta (IL-1β), and Tumor Necrosis Factor-alpha (TNF-α) cytokine genes and susceptibility to chronic hepatitis B infection (CHB) in Iranian families with a history of the disease.
METHODS: This cross-sectional study involved 90 CHB patients, 18 individuals with Recovered hepatitis B virus (HBV) infection, and 30 healthy intrafamilial controls matched for age and sex. Genotyping of the IL-10 (-1082 G > A), IL-18 (-137 G > C), IL-1β (-511 C > T), and TNF-α (-308 G > A) polymorphisms was conducted via polymerase chain reaction with sequence-specific primers (PCR-SSP). Associations with CHB susceptibility were assessed via multivariate logistic regression adjusted for age and sex across multiple genetic models. To address potential non-independence of observations from the same family, we conducted a sensitivity analysis using a generalized estimating equation (GEE) approach with an exchangeable correlation structure, clustering by family.
RESULTS: A significant association was identified between the IL-10-1082 AA genotype and CHB. This genotype was present in 84.4% (76/90) of the CHB patients (p < 0.0001), suggesting an increased likelihood of chronic HBV infection. This association remained in the GEE sensitivity analysis (p < 0.001). For the IL-18-137 G > C single nucleotide polymorphism (SNP), the heterozygous GC genotype was associated with a significantly greater risk of chronicity (p = 0.001). The significance of this finding was retained in the GEE model (p = 0.001). The IL-1β-511 CC genotype was less common in CHB patients (6.7%) than in controls (16.7%), suggesting a potential protective effect. No significant association was found for the TNF-α -308 G > A polymorphism.
CONCLUSIONS: Our findings indicate that genetic variations in IL-10 (-1082 G > A) and IL-18 (-137 G > C) are significant predictors of susceptibility to chronic HBV infection in these familial Iranian clusters. These observational findings suggest a possible role for cytokine gene polymorphisms in the persistence of HBV infection and underscore the need for further studies to explore their utility in genetic screening for high-risk families.
METHODS: This cross-sectional study involved 90 CHB patients, 18 individuals with Recovered hepatitis B virus (HBV) infection, and 30 healthy intrafamilial controls matched for age and sex. Genotyping of the IL-10 (-1082 G > A), IL-18 (-137 G > C), IL-1β (-511 C > T), and TNF-α (-308 G > A) polymorphisms was conducted via polymerase chain reaction with sequence-specific primers (PCR-SSP). Associations with CHB susceptibility were assessed via multivariate logistic regression adjusted for age and sex across multiple genetic models. To address potential non-independence of observations from the same family, we conducted a sensitivity analysis using a generalized estimating equation (GEE) approach with an exchangeable correlation structure, clustering by family.
RESULTS: A significant association was identified between the IL-10-1082 AA genotype and CHB. This genotype was present in 84.4% (76/90) of the CHB patients (p < 0.0001), suggesting an increased likelihood of chronic HBV infection. This association remained in the GEE sensitivity analysis (p < 0.001). For the IL-18-137 G > C single nucleotide polymorphism (SNP), the heterozygous GC genotype was associated with a significantly greater risk of chronicity (p = 0.001). The significance of this finding was retained in the GEE model (p = 0.001). The IL-1β-511 CC genotype was less common in CHB patients (6.7%) than in controls (16.7%), suggesting a potential protective effect. No significant association was found for the TNF-α -308 G > A polymorphism.
CONCLUSIONS: Our findings indicate that genetic variations in IL-10 (-1082 G > A) and IL-18 (-137 G > C) are significant predictors of susceptibility to chronic HBV infection in these familial Iranian clusters. These observational findings suggest a possible role for cytokine gene polymorphisms in the persistence of HBV infection and underscore the need for further studies to explore their utility in genetic screening for high-risk families.