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 B5 or [5) and hepatic fibrosis score (B2 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.

Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients

“…Accordingly, the C allele was the most common allele in both patients and controls. These fi ndings are consistent with previous studies that reported no differences in -607C/A genotype distributions and allele frequencies between patients and controls 26,27 .…”

“…variant -607AA was evident. This fi nding was attributed to an association with milder forms of liver disease in chronic HCV 27 .…”

“…Additionally, complicated cases with cirrhosis and hepatocellular carcinoma (HCC) were associated with the -607C allele. Manohar et al excluded the effe ct of IL-18 gene polymorphisms on susceptibility to chronic HCV infection 27 .…”

Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients

“…We have previously reported association studies of the IL-18, IFN-c, and IL-10 single nucleotide polymorphisms with chronic hepatitis C outcome [25,34]. In accordance with our findings, some significant associations with regard to IL-18 and IFN-c polymorphisms have been observed [30,35]. However, other studies revealed opposing results [36,37].…”

“…Therefore, the majority of studies related to associations between polymorphisms within immune genes and hepatitis C outcome have focused on cytokine genes, and particularly on those participating to Th1 and/or Th2 immune responses [28][29][30][31][32][33]. We have previously reported association studies of the IL-18, IFN-c, and IL-10 single nucleotide polymorphisms with chronic hepatitis C outcome [25,34].…”