Cytokine and apoptosis gene polymorphisms influence the outcome of hepatitis C virus infection

BACKGROUND:Hepatitis C virus (HCV) infection is thought to be chronic and the factors leading to viral clearance or persistence are poorly understood.This study was undertaken to investigate the possibility of a significant relationship between the spontaneous clearance or the persistence of hepatitis C virus (HCV) infection and cytokine and apoptosis gene polymorphisms in Tunisian patients on hemodialysis.METHODS:Polymorphisms of the genes IL-1 (-889 IL-1α,-511 and +3954 IL-1β,IL-1Ra),IL-18 (-137 and-607),IL-12 (-1188) and Apo1/Fas (-670) were determined by PCR-RFLP,PCR-SSP and PCR-VNTR in 100 healthy blood donors and 100 patients infected with HCV and undergoing hemodialysis.The patients were classified into two groups:G1 consisted of 76 active chronic hepatitis patients (positive for HCV RNA) and G2 consisted of 24 hemodialysed patients who spontaneously eliminated the virus (negative for HCV RNA).RESULTS:The frequency of genotype association [-137GC/-607CA] IL-18 was higher in G2 (41.7%) than in G1 (15.8%) (P=0.008;OR=0.26;95% CI,0.10-0.73).We also found a higher frequency of the AA genotype of the Apo1/Fas gene in G2 (41.6%) than in G1 (17.5%) (P=0.026;OR=3.49;95% CI,1.13-10.69).Adjustment for known covariate factors (age,gender and genotype) confirmed these univariate findings and revealed that the genotype association GC-CA of the (-137 and-607) IL-18 gene and the AA genotype of the Apo1/Fas gene were associated with the clearance of HCV (P=0.041 and 0.017,respectively).CONCLUSION:The two genotypes GC-CA of the (-137 and-607) IL-18 polymorphism and the AA genotype of the Apo1/Fas gene influence the outcome of HCV infection in Tunisian patients on hemodialysis.