title: Altered TNF-α and IFN-γ levels associated with PD1 but not TNFA polymorphisms in patients with chronic HBV infection.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, People's Republic of China.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Zhang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.forename: Qunying
authors.initials: Q
authors.lastname: Han
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhu
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
authors.forename: Jinghong
authors.initials: J
authors.lastname: Chen
authors.forename: Sai
authors.initials: S
authors.lastname: Lou
authors.forename: Zhengwen
authors.initials: Z
authors.lastname: Liu
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics*
chemical_list: D017931:DNA Primers; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma