Regulatory polymorphisms in the interleukin-18 promoter are associated with hepatitis C virus clearance

The immune response is critical in determining the outcome of hepatitis C virus (HCV) infection. Interleukin (IL)-18 is a pivotal mediator of the Th1/Th2-driven immune response. Two IL-18 promoter polymorphisms (-607C/A and -137G/C) and their haplotypes were known to affect IL-18 expression. We examined the role played by these polymorphisms in determining HCV clearance or persistence. Genotyping was performed among African American injection drug users with HCV clearance (n = 91) or HCV persistence ( n = 182) and among European Americans with hemophilia who were mainly infected through plasma transfusion. Among injection drug users, IL18 -607A (odds ratio [OR], 3.68 [95% confidence interval{CI}, 1.85-7.34]) and IL18 -137C ( OR, 2.33 [95% CI, 1.24-4.36]) were significantly associated with HCV clearance. A haplotype carrying -607A and -137C (OR, 4.53 [95% CI, 1.77-11.6]) was also strongly associated with viral clearance. No association was found among those with hemophilia. These results suggest that IL-18 promoter polymorphism may affect the outcome of HCV infection in certain groups.