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.

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.