Relationships between IL-1β, TNF-α genetic polymorphisms and HBV infection: A meta-analytical study

Gene. 2021 Jul 30;791:145617. doi: 10.1016/j.gene.2021.145617. Epub 2021 Mar 26.


Background: IL-1β and TNF-α have been demonstrated as pro-inflammatory cytokines to participate in the innate immune response and suppression of HBV infection. However, the exact relationship between IL-1β, TNF-α gene polymorphisms and HBV infection remains unknown. Our study aims to assess the associations between IL-1β, TNF-α gene polymorphisms and HBV infection.

Methods: A systematic literature search of PubMed and Embase databases was conducted through February 2020, and studies that were included in the present meta-analysis should fulfil the following conditions: (1) case-control studies focusing on the associations between IL-1β, TNF-α polymorphisms and HBV infection; (2) patients in the case group should be tested positive for the HBsAg and/or HBV-DNA without liver cirrhosis or hepatocellular carcinoma; (3) the control group including healthy population or HBV spontaneous clearance population; (4) odds ratios (ORs) and their 95% confidence intervals (CIs) could be calculated based on the allele and genotype frequencies provided in articles. The quality of included studies was assessed according to the Newcastle-Ottawa scale (NOS) assessment system. Pooled ORs and 95% CIs were used to analyze the strength of associations. Subgroup analysis was performed according to ethnicity and control type.

Results: In the present meta-analysis, 49 articles including 10,218 cases and 9,557 controls were enrolled and seven polymorphisms (IL-1β rs16944, rs1143634, TNF-α rs1799724, rs1799964, rs1800629, rs1800630, rs361525) were studied. In overall meta-analysis, significant associations were found in IL-1β rs1143634, TNF-α rs1799724 and TNF-α rs1799964. For subgroup analysis under ethnicity, TNF-α rs1799724 and rs1800630 were markedly related to HBV infection in both Asian and Caucasian populations. In terms of control type subgroup, TNF-α rs1799724, rs1799964, rs1800630 were significantly associated with HBV persistence in HBV spontaneous clearance group.

Conclusion: In the present study, we identified that three polymorphisms (IL-1β rs1143634, TNF-α rs1799724, rs1799964) might serve as potential genetic biomarkers in HBV infection.

Keywords: Hepatitis B virus; Interleukin-1beta; Meta-analysis; Odds ratio; SNP; Tumor necrosis factor-alpha.

Publication types

  • Meta-Analysis

MeSH terms

  • Biomarkers
  • Genetic Association Studies
  • Hepatitis B / genetics*
  • Humans
  • Interleukin-1beta / genetics*
  • Polymorphism, Single Nucleotide*
  • Population Groups
  • Publication Bias
  • Tumor Necrosis Factor-alpha / genetics*


  • Biomarkers
  • IL1B protein, human
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha