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: Guoyu Zhang, Zhu Li, Qunying Han, Na Li, Qianqian Zhu, Fang Li, Yi Lv, Jinghong Chen, Sai Lou, Zhengwen Liu
• Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases (Infect Genet Evol) Vol. 11 Issue 7 Pg. 1624-30 (Oct 2011) ISSN: 1567-7257 [Electronic] Netherlands
• PMID: 21712100 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• DNA Primers
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Tumor Necrosis Factor-alpha
• Interferon-gamma

Topics

• Base Sequence
• Case-Control Studies
• DNA Primers (genetics)
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Haplotypes
• Hepatitis B, Chronic (genetics, immunology)
• Host-Pathogen Interactions (genetics, immunology)
• Humans
• Interferon-gamma (blood)
• Polymorphism, Single Nucleotide
• Programmed Cell Death 1 Receptor (genetics)
• Promoter Regions, Genetic
• Tumor Necrosis Factor-alpha (blood, genetics)