Cytokine Gene Polymorphisms and Susceptibility to Chronic Hepatitis B Virus Infection in Familial Clusters From Iran: A Cross-Sectional Study Publisher Pubmed



Aghcheli B ; Behboudi E ; Naderi M ; Hosseini S M ; Tatari M ; Shahramian I ; Khoshnia M ; Besharat S ; Bakhtiari M ; Moradi A
Source: BMC Infectious Diseases Published:2026

Abstract

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. © The Author(s) 2026.