Interleukin 27 polymorphisms in HCV RNA positive patients: is there an impact on response to interferon therapy?

Background: Interleukin 27 (IL-27) has pleiotropic properties that can either limit or enhance immune responses. Recent studies revealed that single nucleotide polymorphisms (SNPs) of the IL-27 promoter region modulate the development of infectious diseases and individual's susceptibility to therapeutic response. Little is known about the relationship between IL-27 single nucleotide polymorphisms and therapy response in patients infected by hepatitis C virus (HCV). In this study we have investigated the potential role of SNPs in the promoter region of IL27 p28 gene (alleles rs153109) on the outcome of HCV infected patients. Methods: rs153109, corresponding to position c.-964A>G of the IL-27 locus, was amplified from genomic DNA extracted from 15 patients with chronic hepatitis C stratified by sustained viral response (SVR), relapser and nonresponder, after treatment with peginterferon-alpha (PegIFN-alpha) combined with ribavirin (RBV). Amplification products were studied by direct sequencing. Results: This method has been applied in a preliminary study on patients with chronic hepatitis C to provide information for a standardized assay useful to genotyping of rs153109 SNPs of IL-27p28. The genotype distribution of the c.-964 A>G polymorphism was more present in patients who did not achieve a SVR. By contrast, the genotype G/G was absent in non-responder and relapser patients. Moreover, the analysis of allelic distribution of rs153109 highlighted a predominance of allele A in all genotypes in spite of allele G. Conclusions: Our work provides preliminary information for a standardized method potentially useful for genotyping rs153109, and suggests its utility as a candidate approach to evaluate IL-27 p28 polymorphisms as additional clinical predictors of response to therapies in HCV infected patients.

Interleukin 27 (IL-27) has pleiotropic properties that can either limit or enhance immune responses. Recent studies revealed that single nucleotide polymorphisms (SNPs) of the IL-27 promoter region modulate the development of infectious diseases and individual's susceptibility to therapeutic response. Little is known about the relationship between IL-27 single nucleotide polymorphisms and therapy response in patients infected by hepatitis C virus (HCV). In this study we have investigated the potential role of SNPs in the promoter region of IL27 p28 gene (alleles rs153109) on the outcome of HCV infected patients. METHODS: rs153109, corresponding to position c.-964A>G of the IL-27 locus, was amplified from genomic DNA extracted from 15 patients with chronic hepatitis C stratified by sustained viral response (SVR), relapser and non-responder, after treatment with peginterferon-α (PegIFN- α) combined with ribavirin (RBV). Amplification products were studied by direct sequencing. RESULTS: This method has been applied in a preliminary study on patients with chronic hepatitis C to provide information for a standardized assay useful to genotyping of rs153109 SNPs of IL-27p28. The genotype distribution of the c.-964 A>G polymorphism was more present in patients who did not achieve a SVR. By contrast, the genotype G/G was absent in non-responder and relapser patients. Moreover, the analysis of allelic distribution of rs153109 highlighted a predominance of allele A in all genotypes in spite of allele G. CONCLUSIONS: Our work provides preliminary information for a standardized method potentially useful for genotyping rs153109, and suggests its utility as a candidate approach to evaluate IL-27 p28 polymorphisms as additional clinical predictors of response to therapies in HCV infected patients