Production of tumor necrosis factor (TNF)-α and interferon (IFN)-γ, two important cytokines involved in the immune responses to hepatitis B virus (HBV) infection, may be influenced by gene polymorphisms of TNFA and PD1. This study determined the associations of serum TNF-α and IFN-γ levels with TNFA promoter -308 G/A and -238 G/A and PD1 -606 G/A and +8669 G/A polymorphisms in chronic HBV patients and healthy controls. The results showed that TNFA polymorphisms had no association with TNF-α and IFN-γ levels. However, patients with PD1 -606 AA genotype had lower TNF-α and IFN-γ levels. HBV infection in patients with PD1 +8669 GG genotype altered TNF-α to higher levels compared with controls. HBV patients with PD1 -606A/+8669A or -606G/+8669A haplotype tended to have significantly lower or higher TNF-α and IFN-γ levels, respectively. Combined with the lower frequency of PD1 +8669 GG genotype in HBV patients and the minor contribution of PD1 -606 G allele to the protective role of PD1 +8669 G allele, it is indicated that PD1 -606 G allele in a haplotype with PD1 +8669 G allele may have strong inhibitory effect on programmed cell death-1 (PD-1) function and thus reduce its negative impact on T-cell activation and function, leading to higher cytokines secretion and exhibiting a protective role, while the minor predisposing role of PD1 -606 AA genotype to chronic HBV infection may be incurred by decreasing the inhibitory effect on PD-1 function.
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