Abstract
BackgroundSingle-nucleotide polymorphisms (SNPs) in tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene have been linked to inflammatory, immunological and malignant diseases. Hepatitis B virus (HBV) infection is characterized by immunopathogenesis. This study investigated the association of rs2230926, a nonsynonymous SNP in TNFAIP3 gene, with chronic HBV infection.MethodsFour hundred and fifty-five patients with chronic HBV infection with clinical diseases of chronic hepatitis (n = 183), liver cirrhosis (n = 167) and hepatocellular carcinoma (n = 105), 92 HBV infection resolvers and 171 healthy controls were included. All subjects were of Chinese Han ethnicity. Genotyping of rs2230926 was carried out by polymerase chain reaction-restriction fragment length polymorphism method.ResultsThe gender and age between HBV patients, HBV infection resolvers and healthy controls had no statistical difference. The genotypes of rs2230926 in HBV patients, HBV infection resolvers and healthy controls are in Hardy-Weinberg equilibrium. The genotype and allele frequencies of TNFAIP3 rs2230926 polymorphism between HBV patients, HBV infection resolvers and healthy controls had no significant difference. The genotype and allele frequencies of TNFAIP3 rs2230926 polymorphism between HBV patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma also showed no significant difference.ConclusionsThe TNFAIP3 rs2230926 polymorphism is not suggested to be associated with the susceptibility of chronic HBV infection or the progression of HBV-related diseases in this study. Replicative studies and studies in large control and HBV patient populations of different ethnicity by genotyping more polymorphisms in TNFAIP3 gene are needed.
Highlights
Single-nucleotide polymorphisms (SNPs) in tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene have been linked to inflammatory, immunological and malignant diseases
Patients were diagnosed as a clinical disease of chronic hepatitis (CH), liver cirrhosis (LC) or hepatocellular carcinoma (HCC) based on history of Hepatitis B virus (HBV) infection, HBsAg/anti-HBs, HBeAg/anti-HBe and anti-HBc serostatus, HBV DNA level, biochemical liver function, α-fetoprotein (AFP) level, and ultrasonography and/or computerized tomography (CT)/ magnetic resonance imaging (MRI) as described previously [14]
The genotypes of rs2230926 in HBV patients, HBV infection resolvers and healthy controls are in Hardy-Weinberg equilibrium (P > 0. 05, Table 1)
Summary
Single-nucleotide polymorphisms (SNPs) in tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene have been linked to inflammatory, immunological and malignant diseases. This study investigated the association of rs2230926, a nonsynonymous SNP in TNFAIP3 gene, with chronic HBV infection. Hepatitis B virus (HBV) infection is a major cause of liver disease. Because the excess of inhibitory molecules is among the critical factors driving T cell exhaustion in chronic HBV infection, blockade of these inhibitory molecules including programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) has been demonstrated to reconstitute the potential of functional HBV-specific T cells [11,12]. Single-nucleotide polymorphisms (SNPs) in PD1 [13], CTLA4 [14] and TIM3 [15] have been demonstrated to be associated with the disease progression of chronic HBV infection. The role of these molecules in chronic HBV infection appeared to be non-redundant and the rescue of HBV T cell specificities by their blockade was incomplete and not all patients responded to these strategies, suggesting the possible role of other inhibitory molecules
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