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

Abstract

Introduction: 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. Aim: To investigate the association between -607 or -137 polymorphism with susceptibility and severity of HCV infection. Patients and methods: 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. Results: 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; R² = 0.631) and stage of fibrosis (38.7% vs. 16.7%, P = 0.008; OR = 0282, CI = 0.134-0.596; R² = 0.434). Conclusions: 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.