IL-18 variant increases risk of enhanced HBV DNA replication in chronic hepatitis

Immunol Lett. 2020 Dec:228:70-75. doi: 10.1016/j.imlet.2020.10.002. Epub 2020 Oct 7.

Abstract

Background: The outcome ofhepatitis B (HBV) infection is influenced by immune responses and host genetics. Interleukin-18 (IL-18) is a determinant factor in controlling the balance of Th1/Th2 during antiviral response.Weexamine therole of two functional polymorphisms -607A/C and-137A/C inIL-18 gene with risk of chronic HBV infection.

Methods and results: Genomic DNA isolates were obtained from 200 seropositive cases stratified according to their HBV DNA loads, and 200 blood donorsas a control population. Genotypes of the two polymorphisms were identified by ARMS-PCR method. The -607A allele, the-607AA and -607AC genotypes were associated with increased risk to develop chronic HBV infection (1.98, 5.11 and 3.5-fold risks, respectively). By contrast, the -137C minor allele and CG genotype had protected effects against chronic HBV infection. We found that -607A allele, -607AA and -607AC genotypes were significantly more frequent in patient's group with high HBV DNA levels compared to patient group with low HBV DNA level. Additionally, they were associated with increased 1.72, 6.04 and 3.28-fold risk of high HBV DNA replication. Patients carrying "-607A/-137 C" or "-607A/-137 G" haplotypes presented a high risk to develop chronic HBV infection (OR = 3.27; OR = 4.32, respectively).

Conclusions: Taken together, our data suggest that theIL-18 -607A/C functional polymorphism was associated with susceptibility to enhanced replicative form of HBV DNA in chronic infection.

Keywords: Chronic HBV infection; DNA replication; Interleukin-18; Polymorphism; Susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • DNA Replication*
  • DNA, Viral / biosynthesis*
  • DNA, Viral / genetics
  • Female
  • Genetic Predisposition to Disease
  • Haplotypes
  • Hepatitis B virus / genetics
  • Hepatitis B virus / growth & development*
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / virology
  • Humans
  • Interleukin-18 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Protective Factors
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Tunisia
  • Virus Replication*
  • Young Adult

Substances

  • DNA, Viral
  • IL18 protein, human
  • Interleukin-18