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

BackgroundHepatitis 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.MethodsPolymorphisms 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).ResultsThe 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).ConclusionThe 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.