title: Role of serum level and genetic variation of IL-28B in interferon responsiveness and advanced liver disease in chronic hepatitis C patients.
abstract: Interleukin-28B (IL-28B) is suspected to be associated with response to treatment and one of the basic immunological backgrounds in liver transplant candidate (LTC). We aimed to assess whether genotypes of IL-28B can play a role in therapeutic response or advanced stages of liver disease. A total of 364 subjects were genotyped for IL-28B rs12979860 and rs8099917 SNPs using PCR-RFLP assay. Moreover, IL-28 serum level, HCV loads, and genotype were performed. A significant increase was observed in the frequencies of unfavorable rs12979860 genotypes/CT + TT in the chronic hepatitis C (CHC) and LTC groups. In the case of rs8099917, CHC group had a significantly higher frequency of unfavorable genotypes/GT + GG compared to the healthy group. IL-28B serum level was also significantly higher in healthy group compared with the CHC and LTC groups. There were no differences in the distribution of the IL-28B genotypes and haplotypes between responder and non-responder patients. Our results suggest, for the first time, that unfavorable rs12979860 genotypes can be considered one of the important immunological backgrounds in the Iranian LTC population that was confirmed with the lower IL-28 serum level compared to healthy group. Besides, there was a possible association of favorable IL-28B genotypes with lower odds of susceptibility to CHC infection but no support for a positive association between analyzed SNPs and an outcome of therapy. Moreover, non-CT haplotypes may be regarded as a genetic risk factor that can increase the chance of infection with HCV and progression toward end-stage HCV-related liver disease.
authors.affiliation: Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Abdolvahab
authors.initials: A
authors.lastname: Alborzi
authors.affiliation: Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. thashem@sums.ac.ir.
authors.forename: Tayebeh
authors.initials: T
authors.lastname: Hashempour
authors.affiliation: Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Moayedi
authors.affiliation: Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Musavi
authors.affiliation: Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Pouladfar
authors.affiliation: Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahin
authors.initials: S
authors.lastname: Merat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015415:Biomarkers; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007378:Interleukins / Q000097:blood* / Q000235:genetics*; D008099:Liver / Q000473:pathology* / Q000821:virology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D015415:Biomarkers; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: HCV; IL-28B; Liver transplant candidate; Treatment outcome