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-1alpha, -511 and +3954 IL-1beta, 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.