Combined analysis of interferon-γ and interleukin-10 gene polymorphisms and chronic hepatitis C severity

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

“…The logistic regression analysis showed that, in chronic hepatitis C, a predominant pro-inflammatory profile stemming from the co-inheritance of 3-4 putative high-risk genotypes of IL-18, IFN-c, and IL-10 is an independent factor associated with a greater risk for liver cirrhosis. Interestingly, this result seems to be more relevant compared to those we reported previously on each individual polymorphism [25,34]. It underscores the hypothesis that the pro/antiinflammatory response imbalance toward a pro-inflammatory cytokine profile is associated with HCV-related fibrosis aggressiveness and the risk of cirrhosis [8-11, 26, 53, 63].…”

“…Genotype frequency analyses of IL-18, IFN-c, and IL-10 gene polymorphisms with regard to chronic hepatitis C severity were previously published [25,34]. Polymorphism genotype distribution in Tunisian HCV-infected patients with or without cirrhosis was summarized in Table 2.…”

“…Cytokine production varies among individuals and is associated with certain mutations within the coding and the regulatory regions [27]. In a previous study, we reported that IFN-c ?874T allele or a pro/anti-inflammatory response imbalance mediated by polymorphisms in IFN-c and IL-10 genes may influence the outcome of chronic HCV infection [34]. Furthermore, we previously suggested that the carriage of at least one allele C at position -607 or G at position -137 of IL-18 gene seems to be a risk factor for developing more severe forms of chronic hepatitis in Table 2 Summary of genotype frequencies of polymorphisms in IL-18, IFN-c, and IL-10 genes in Tunisian chronic hepatitis C patients with or without liver cirrhosis [25,34] Genotypes (n) Liver cirrhosis (-) Tunisian HCV-infected patients [25].…”

“…The IL-18 -607C/A, IL-18 -137G/C, IFN-c ?874T/A and IL-10 -1082G/A genotypes were determined as previously described [25,34].…”

“…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]. In accordance with our findings, some significant associations with regard to IL-18 and IFN-c polymorphisms have been observed [30,35].…”