IL-17 Genetic Variations Increase The Risk of Cirrhotic/Hepatocellular Carcinoma in Patients with Hepatitis B Virus Infection

Iran J Immunol. 2021 Jun;18(2):130-140. doi: 10.22034/iji.2021.88020.1852.

Abstract

Background: Genetic variation in immune regulatory genes might influence the HBV infection outcome.

Objective: This study aimed to determine the association of IL-17A rs2275913 (G197A), IL-17F rs763780 (A7488G), and IL-23R rs10889677 (C2370A) gene polymorphisms, as well as the emerged haplotypes in the individual infected by HBV and to investigate their association with the infection outcome.

Materials and methods: 300 chronic HBV infections with Cirrhotic/Hepatocellular carcinoma(C/HCC), chronic active (CA), and asymptomatic carrier (AC) and 38 individuals whose infection was spontaneously cleared (SC) were enrolled. Genomic DNA was extracted, and IL-17A/F and IL-23R genotyping were performed by using the PCR-RFLP method.

Results: Out of 338 subjects, 238 and 100 were respectively male and /female with a mean age of 47.61±13.41. The frequency of GA genotype (p=0.01) and A alleles (p=0.001) of IL-17A rs2275913 (G197A), as well as the frequency of AA genotype (p=0.014) and A alleles (p=0.018) of IL-17F rs763780 (A7488G) gene locus, was found to be significantly higher in the C/HCC than CA and AC groups. Furthermore, the frequency of GA and AG haplotype in CA individuals was higher than those with C/HCC and AC (p=0.003). Also, the GG haplotype was higher in AC individuals than those with C/HCC (P=0.022), and the AA haplotype was higher in C/HCC individuals than the CA patients (P=0.001).

Conclusion: Our findings suggest that A allele and GA genotype at IL-17A rs2275913 (G197A), as well as A allele and AA genotype at IL-17F rs763780 (A7488G) locus, might be associated with increased risk of C/HCC among patients with hepatitis B virus infection.

MeSH terms

  • Adult
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / genetics*
  • Female
  • Genotype
  • Haplotypes
  • Hepatitis B / complications*
  • Hepatitis B / genetics
  • Humans
  • Interleukin-17 / genetics*
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / genetics*
  • Liver Neoplasms / etiology
  • Liver Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Interleukin / genetics
  • Risk
  • Young Adult

Substances

  • IL17A protein, human
  • IL17F protein, human
  • IL23R protein, human
  • Interleukin-17
  • Receptors, Interleukin