Association of IL-18 promoter polymorphism with liver disease severity in HCV-infected patients

Abstract

Interleukin (IL)-18 plays an important dual role in Th1 polarization and viral clearance, as well as in the development of liver fibrosis. Single-nucleotide promoter polymorphisms influence the transcription of IL-18 mRNA. Promoter polymorphisms are linked to delayed virus clearance and disease susceptibility in many diseases. However, there is no information about their role in hepatitis C virus (HCV) infection. To investigate the association between -607 or -137 polymorphism with susceptibility and severity of HCV infection. Two hundred and four serologically proven patients with chronic HCV infection and 350 matched healthy controls were included in this study. Patients were segregated in 2 groups: group A with mild liver disease and group B with severe liver disease on the basis of histological activity index (HAI </=5 or >5) and hepatic fibrosis score (</=2 or >2). IL-18 promoter genotyping was performed with sequence-specific primers. There was no significant difference in the frequencies of -607 and -137 allelic distribution in patients and controls. The -607 A/A allele was more common in group A patients with mild liver disease than in patients with severe liver disease on the basis of HAI (38.6% vs. 21%, P = 0.05; odds ratio [OR] = 0.424, confidence interval [CI] = 0.233-0.773; R (2) = 0.631) and stage of fibrosis (38.7% vs. 16.7%, P = 0.008; OR = 0282, CI = 0.134-0.596; R (2) = 0.434). IL-18 promoter polymorphism at -607 position with A/A allele is a potential protective marker, as it is associated with milder liver disease in patients with chronic HCV infection.