IL-18 and CD14 variants in chronic HBV predisposition: a case-control study with in silico analyses focused on

Mohammad Sarhadi1, Elham Pahlavani2, Niloufar Hosseini Razavi1

  • 1Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.

Insights

Genetic variations in IL-18 and CD14 influence chronic Hepatitis B virus (HBV) infection risk. The IL-18-rs187238 C>G variation acts as a protective factor against chronic HBV, while other combined genotypes increase risk.

Area of Science:

  • Immunogenetics
  • Hepatology
  • Bioinformatics

Background:

  • Hepatitis B virus (HBV) infection is a global health concern, potentially leading to severe liver diseases like cirrhosis and hepatocellular carcinoma.
  • Individual differences in immune response, influenced by genetic variations in cytokines, affect HBV clinical manifestations.
  • Immunogenetic profiling aids in understanding disease susceptibility and progression.

Purpose of the Study:

  • To investigate the association between specific genetic variations in the promoter regions of IL-18 (rs187238 C>G, rs1946518 T>G) and the intronic region of CD14 (rs2569190 A>G) and the risk of chronic HBV infection.
  • To analyze the functional impact of these genetic variations using bioinformatics tools.

Main Methods:

  • Genotyping of 400 individuals (200 cases, 200 controls) using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).
  • Bioinformatic analysis to assess genomic conservation, transcription, splicing, and protein interactions.
  • Statistical analysis to determine the association between genotypes, haplotypes, and chronic HBV risk.

Main Results:

  • The IL-18-rs187238 C>G variation showed a protective effect against chronic HBV (OR=0.62, 95% CI: 0.46-0.83, p=0.002).
  • Specific combined genotypes (TG/CC/AA, TG/CC/AG, TT/CC/AG, GG/CC/AA) significantly increased chronic HBV risk (p<0.05).
  • IL-18 G/T and G/G haplotypes were associated with reduced risk (p<0.05). Bioinformatics suggested functional roles for IL-18-rs187238 C>G and CD14-rs2569190 A>G variations.

Conclusions:

  • The IL-18-rs187238 C>G polymorphism is a significant protective factor against chronic HBV infection.
  • Genetic variations in IL-18 and CD14 play a role in modulating the risk of chronic HBV.
  • Further research in larger, diverse populations is warranted to confirm these findings and explore underlying mechanisms.

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