Association of IL-6 G-174C (rs1800795) variant with the susceptibility to hepatocellular carcinoma in patients with chronic hepatitis

J Egypt Natl Canc Inst. 2024 Oct 21;36(1):32. doi: 10.1186/s43046-024-00238-y.

Abstract

Aim: An ineffective immune response resulting from dysregulation of cytokine production might encourage viral persistence and cause chronic viral hepatitis to worsen. This study examined the relationship between alterations in interleukin-6 (IL-6) levels and the IL-6 - 174 G > C (rs1800795) polymorphism, as well as how this polymorphism affects the development and progression of chronic hepatitis brought on by hepatitis B (HBV) and hepatitis C (HCV) into hepatocellular carcinoma (HCC).

Patients and methods: Whole blood samples from 126 Egyptian patients with HCC (111 with HCV and 15 with HBV), as well as 126 age- and sex-matched healthy individuals, were used to extract DNA. Using PCR-based allele-specific amplification (ASA), the existence of the IL-6 G-174C polymorphism was investigated. Additionally, each participant's serum IL-6 levels were determined using an enzyme-linked immunosorbent assay (ELISA).

Results: The primary observations revealed that HCC patients had greater serum levels of IL-6 compared to the control groups (p < 0.001). Patients with the variant (CG and GG) genotype in the HCC group were found to have more disease severity indicated by higher levels of alpha-fetoprotein (AFP) and a higher ascites grade, as well as increased inflammatory activity as defined by higher levels of IL-6 and C-reactive protein (CRP) (p < 0.001 for both) in comparison to patients with the wild-type (CC) genotype (p < 0.001 and p = 0.002, respectively).

Conclusion: The rs1800795 SNP in the IL-6 gene was associated with increased inflammatory activity and high levels of IL-6, indicating that this SNP may play a role in the development of HCC in Egyptian patients with chronic viral hepatitis.

Keywords: HCC; IL-6; Polymorphism; Viral hepatitis.

MeSH terms

  • Adult
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / etiology
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / virology
  • Case-Control Studies
  • Egypt / epidemiology
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Hepatitis B, Chronic* / blood
  • Hepatitis B, Chronic* / complications
  • Hepatitis B, Chronic* / genetics
  • Hepatitis B, Chronic* / virology
  • Hepatitis C, Chronic* / blood
  • Hepatitis C, Chronic* / complications
  • Hepatitis C, Chronic* / genetics
  • Hepatitis C, Chronic* / virology
  • Humans
  • Interleukin-6* / blood
  • Interleukin-6* / genetics
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / etiology
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / virology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • Interleukin-6
  • IL6 protein, human