title: 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.
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.
authors.affiliation: Genetics & Bio-Engineering Department, Yeditepe University, Kayisdagi, 34755 Istanbul, Turkey. mkorachi@yeditepe.edu.tr
authors.forename: May
authors.initials: M
authors.lastname: Korachi
authors.forename: Nurgül
authors.initials: N
authors.lastname: Ceran
authors.forename: Riza
authors.initials: R
authors.lastname: Adaleti
authors.forename: Adil
authors.initials: A
authors.lastname: Nigdelioglu
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sökmen
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D016174:Hepacivirus / Q000502:physiology; D006515:Hepatitis B virus / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000235:genetics* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000235:genetics* / Q000821:virology; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017471:Receptors, Interferon / Q000235:genetics*; D014421:Turkey; D019562:Viral Load; D000096743:Interferon gamma Receptor
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C494257:IRF1 protein, human