Interleukin-1, interleukin-10 and tumour necrosis factor-alpha gene polymorphisms in hepatitis C virus infection: an investigation of the relationships with spontaneous viral clearance and response to alpha-interferon therapy Constantini PK, Wawrzynowicz-Syczewska M, Clare M, BoronKaczmarska A, McFarlane IG, Cramp ME, Donaldson PT. Interleukin-1, interleukin-10 and tumour necrosis factor-alpha gene polymorphisms in hepatitis C virus infection: an investigation of the relationships with spontaneous viral clearance and response to alpha-interferon therapy. Abstract: Background/Aims: Though there is a consensus that the HLA DQB1*0301 allele is important in untreated HCV clearance, this association is not universal and a number of genes outside the major histocompatibility complex may also play a role in host responses to HCV infection. Prime candidates, at present, are the genes encoding pro-in¯ammatory and immuno-regulatory cytokines. The aim of this study was to investigate the relationship between a number of these candidate genes and both spontaneous and treatment related clearance of hepatitis C virus infection. Methods: Three members of the interleukin-1 gene family: IL-1A, IL-1B and IL-1RN, three polymorphic sites in the interleukin-10 gene promoter (À 1082, À819, À592) and two in the tumour necrosis factor-alpha promoter (À 308, À238) were studied in two independent DNA banks, each with appropriate controls. Standard PCR-based genotyping techniques were used. Results: No signi®cant difference in the distribution of any of the polymorphisms was found in either study set. Conclusions: These ®ndings in two large groups suggest that future investigations should focus on other candidate genes and may support the view that MHC-encoded susceptibility to chronic HCV infection may be determined by MHC class II rather than MHC class III genes.