title: Variation in genes encoding for interferon λ-3 and λ-4 in the prediction of HCV-1 treatment-induced viral clearance.
abstract: OBJECTIVE
  In patients with chronic HCV-1 infection, recent evidences indicate that determination of a dinucleotide polymorphism (ss469415590, ΔG/TT) of a new gene, designated IFN λ-4, might be more accurate than the 12979860CC type of the IL28B locus in predicting sustained virological response (SVR) following peg-interferon and ribavirin. In addition, combined genotyping of different SNPs of the IL28B locus was shown to help dissect patients most prone to SVR among those with rs12979860CT. We examined whether single or combined genotyping of two IL28B SNPs, rs12979860 and rs8099917, and ss469415590 variation might improve the prediction of SVR.
  
  
  RESULTS
  In the study cohort of 539 patients, 38% had SVR. The SNPs 12979860CC, rs8099917TT, and rs469415590TT/TT correlated significantly with SVR (68%, 50%, and 67%). Carriers of either the triplotype rs12979860CC_ss469415590TT/TT_rs8099917TT or the diplotype rs12979860CC_ss469415590TT/TT had the highest SVR rate (72%). In carriers of the rs12979860 T allele, neither the rs8099917 nor the ss469415590 improved the response prediction. After pooling this finding with data from previous studies, in rs12979860 T heterozygous individuals the co-presence of the rs8099917TT SNP was associated with improved response prediction.
  
  
  CONCLUSIONS
  In HCV-1 patients, the rs12979860 polymorphism appeared as the hit SNP better predicting response following peg-interferon and ribavirin treatment. Additional ss469415590 or rs8099917 genotyping had no added benefit for response prediction. In the subset of carriers of the rs12979860 T allele, genotyping of the rs8099917 SNP was unhelpful in the present investigation, but may inform clinical prediction of treatment response when our data were pooled with previous investigations.
authors.affiliation: Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Palmieri
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Ippolito
authors.forename: Maurizio
authors.initials: M
authors.lastname: Margaglione
authors.forename: Maria R
authors.initials: MR
authors.lastname: Valvano
authors.forename: Domenica
authors.initials: D
authors.lastname: Gioffreda
authors.forename: Massimo
authors.initials: M
authors.lastname: Fasano
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Corritore
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
authors.forename: Nicola
authors.initials: N
authors.lastname: Andriulli
authors.forename: Filomena
authors.initials: F
authors.lastname: Morisco
authors.forename: Lydia
authors.initials: L
authors.lastname: Giannitrapani
authors.forename: Anna
authors.initials: A
authors.lastname: Latiano
authors.forename: Rosanna
authors.initials: R
authors.lastname: Fontana
authors.forename: Pietro
authors.initials: P
authors.lastname: Gatti
authors.forename: Paolo
authors.initials: P
authors.lastname: Tundo
authors.forename: Michele
authors.initials: M
authors.lastname: Barone
authors.forename: Raffaele
authors.initials: R
authors.lastname: Cozzolongo
authors.forename: Teresa
authors.initials: T
authors.lastname: Santantonio
authors.forename: Angelo
authors.initials: A
authors.lastname: Andriulli
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human; C100416:peginterferon alfa-2a
keywords: HCV; IL28B/interferon lambda-3 gene; chronic hepatitis; interferon lambda-4 gene; peg-interferon/ribavirin