Strong association of functional polymorphism in IL-12B with susceptibility to chronic hepatitis B in Tunisia

J Med Virol. 2021 Aug;93(8):4949-4956. doi: 10.1002/jmv.26946. Epub 2021 Apr 1.

Abstract

Background: The chronicity or clearance of hepatitis B virus (HBV) infection depends on viral and genetic variables. The immune response against HBV is thought to be responsible for viral persistence or clearance. Cytokines such as interleukin 1-2B (IL1-2B) involved in the T-helper 1 system are key mediators in the defence mechanisms against viral infection and play a role in the regulation of HBV clearance during infection. We aimed to examine whether the polymorphic variant TaqI polymorphism in the 3'-untranslated region (3'-UTR; rs3212227) suspected to modulate interleukin-levels of IL-12B has an influence on the risk of development of chronicity after HBV exposure.

Methods: Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method for 236 patients with chronic hepatitis B (CHB) and 240 controls from different cities of Tunisia recruited in the Pasteur Institute of Tunisia between January 2017 and December 2018.

Results: We found that the IL-12B polymorphism was associated with a significantly increased risk of CHB in patients (p = 1 × 10-3 ; χ 2 = 10.31 and odds ratio [OR] = 2.14; 95% confidence interval [CI] = 1.30-3.52) when AC/CC variant genotypes were compared with the wild-type AA homozygote. Statistical significance was found when CHB-males were compared with CHB-females (p = 2 × 10-7 ; χ 2 = 26.62 and p = 1 × 10-3 ; χ 2 = 10.36, for genotypic and allelic frequencies, respectively). Also, CHB-patients carrying C-allele less than 50-years were at an increased risk of developing chronic HBV infection than patients more than 50-years (p = 6.1 × 10-5 ; χ 2 = 16.07).

Conclusions: These results suggest that the C-allele would affect susceptibility to chronicity after HBV exposure in Tunisian patients especially for males less than 50-years. Age and sex have an influence on this polymorphism in CHB Tunisian patients.

Keywords: IL-12B; Hepatitis B virus; polymerase chain reaction; polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Alleles
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Hepatitis B virus
  • Hepatitis B, Chronic / epidemiology
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Interleukin-12 Subunit p40 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Tunisia

Substances

  • 3' Untranslated Regions
  • IL12B protein, human
  • Interleukin-12 Subunit p40