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Published on: October 20, 2021
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.
Abstract:
Hepatitis B virus (HBV), a vaccine-avoidable infection, is a health concern worldwide, leading to liver disorders such as acute self-constraint and chronic hepatitis, liver failure, hepatic cirrhosis, and even hepatocellular carcinoma if untreated. 'Immunogeneticprofiling', genetic variations of the pro- and anti-inflammatory cytokines responsible for regulating the immune responses, cause person-to-person differences and impact the clinical manifestation of the disease. The current experimental-bioinformatics research was conducted to examine whether promoteric IL-18-rs187238 C > G and -rs1946518 T > G and intronic CD14-rs2569190 A > G variations are associated with chronic HBV. A total of 400 individuals (200 in each case and control group) participated in the study and were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The data was also assessed bioinformatics-wise for conservation, genomic transcription and splicing, and protein interactions. Findings proposed that unlike the IL-18-rs1946518 T > G and CD14-rs2569190 A > G, the IL-18-rs187238 C > G is a protector against chronic HBV (odds ratio [OR] = 0.62, 95% confidence intervals [CI]: 0.46-0.83, and p = 0.002). The TG/CC/AA, TG/CC/AG, TT/CC/AG, and GG/CC/AA combined genotypes significantly increased chronic HBV risk (p < 0.05), while the IL-18 G/T and G/G haplotypes lessened it (p < 0.05). Moreover, IL-18-rs1946518 T > G is in the protected genomic regions across mammalian species. In contrast to the IL-18-rs1946518 T > G, IL-18-rs187238 C > G is likely to create novel binding sites for transcription factors, and the CD14-rs2569190 A > G presumably changed the ribonucleic acid splicing pattern. More research on larger populations and other ethnicities is required to authenticate these results.
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