An association study of functional polymorphic genes IRF-1, IFNGR-1, and IFN-γ with disease progression, aspartate aminotransferase, alanine aminotransferase, and viral load in chronic hepatitis B and C

Int J Infect Dis. 2013 Jan;17(1):e44-9. doi: 10.1016/j.ijid.2012.08.004. Epub 2012 Oct 3.

Abstract

Background: Investigational approaches based on genome-wide association studies have proven useful in identifying genetic predictors for many diseases, including susceptibility to chronic hepatitis B and C. In these studies, the majority of genetic variants that have shown a positive association have been identified in genes involved in the immune response. In this study IFN-γ, IFNGR-1, and IRF-1 genes were analyzed for their role in susceptibility to the development of chronic hepatitis B and chronic hepatitis C in a Turkish population.

Methods: Polymorphic genes IRF-1 (-410, -388), IFNGR-1 (-56, -611), and IFN-γ (+874) were analyzed in a total of 400 individuals: 100 chronic hepatitis B patients, 100 hepatitis B carriers, 100 chronic hepatitis C patients, and 100 healthy controls. A single base primer extension assay was used. Correlations between genes and gender, viral load, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were also investigated.

Results: The IRF-1 gene at positions -388 and -410 were observed to be candidate gene markers for susceptibility to the development of chronic hepatitis B and C (p<0.05). IFN-γ +874 and IFNGR-1 (-56 and -611) correlated with chronic hepatitis B but not chronic hepatitis C. Correlation of functional genotype with viral load and AST and ALT levels revealed an association of IFN-γ +874 and IFNGR-1 -611 with chronic hepatitis C and IFN-γ +874 with viral load and chronic hepatitis B (p<0.05).

Conclusions: Findings suggest that IFN-γ (+874), IRF-1 (-410, -388), and IFNGR-1 (-56, -611) are candidate gene markers for determining patient susceptibility to the development of chronic hepatitis B and C.

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood*
  • Aspartate Aminotransferases / blood*
  • Case-Control Studies
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Hepacivirus / physiology
  • Hepatitis B virus / physiology
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / virology
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon Regulatory Factor-1 / genetics
  • Interferon gamma Receptor
  • Interferon-gamma / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptors, Interferon / genetics*
  • Turkey
  • Viral Load

Substances

  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Receptors, Interferon
  • Interferon-gamma
  • Aspartate Aminotransferases
  • Alanine Transaminase