title: IL28B and IL10R -1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort.
abstract: BACKGROUND
  Previous studies have shown that single nucleotide polymorphisms (SNP) in IL28B and IL10R are associated with sustained virological response (SVR) in chronic hepatitis C patients treated with pegilated interferon plus ribavirin (P/R). The present study extends our earlier investigations on a large East-Central European cohort. The allele frequencies of IL28B and IL10R in genotype 1 HCV infection were compared with that of healthy controls for the purpose of examining the relationship between the polymorphisms and the SVR to P/R treatment.
  
  
  METHODS
  A total of 748 chronic HCV1 infected patients (365 male, 383 female; 18-82 years) and 105 voluntary blood donors as controls were enrolled. Four hundred and twenty HCV patients were treated with P/R for 24-72 weeks, out of them 195 (46.4%) achieved SVR. The IL28 rs12979860 SNP was determined using Custom Taqman SNP Genotyping Assays. The IL10R -1087 (also known as IL10R -1082 (rs1800896) promoter region SNP was determined by RT-PCR and restriction fragment length polymorphism analysis.
  
  
  RESULTS
  The IL28B CC genotype occurred with lower frequency in HCV patients than in controls (26.1% vs 51.4%, p<0.001). P/R treated patients with the IL28B CC genotype achieved higher SVR rate, as compared to patients with CT (58.6% vs 40.8%, p=0.002). The prevalence of IL10R -1087 GG genotype was lower in patients than in controls (31.8 % vs 52.2%, p<0.001). Among patients achieving SVR, the IL10R -1087 GG genotype occurred with higher frequency than the AA (32.0% vs 17.4%, p=0.013). The IL28B T allele plus IL10R A allele combination was found with higher prevalence in patients than in controls (52% vs 20.7%, p<0.001). The IL28B CC plus IL10R A allele combination occurred with higher frequency among patients with SVR than in non-responders (21.3% vs 12.8%, p=0.026). Both the IL28B CC plus IL10R GG and the IL28B CC plus IL10R A allele combinations occurred with lower frequency in patients than in controls.
  
  
  CONCLUSIONS
  In our HCV1 patients, both the IL28B CC and IL10R GG genotypes are associated with clearance of HCV. Moreover, distinct IL28B and IL10R allele combinations appear to be protective against chronic HCV1 infection and predictors of response to P/R therapy.
authors.affiliation: First Department of Medicine, University of Pécs, Rákóczi u, 2, 7623 Pécs, Hungary. alajos.par@aok.pte.hu.
authors.forename: Alajos
authors.initials: A
authors.lastname: Pár
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pár
authors.forename: István
authors.initials: I
authors.lastname: Tornai
authors.forename: Ferenc
authors.initials: F
authors.lastname: Szalay
authors.forename: Dalma
authors.initials: D
authors.lastname: Várszegi
authors.forename: Edit
authors.initials: E
authors.lastname: Fráter
authors.forename: Mária
authors.initials: M
authors.lastname: Papp
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lengyel
authors.forename: János
authors.initials: J
authors.lastname: Fehér
authors.forename: Márta
authors.initials: M
authors.lastname: Varga
authors.forename: Judit
authors.initials: J
authors.lastname: Gervain
authors.forename: János
authors.initials: J
authors.lastname: Schuller
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Nemes
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Péterfi
authors.forename: Anna
authors.initials: A
authors.lastname: Tusnádi
authors.forename: Béla
authors.initials: B
authors.lastname: Hunyady
authors.forename: Attila
authors.initials: A
authors.lastname: Haragh
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szinku
authors.forename: Aron
authors.initials: A
authors.lastname: Vincze
authors.forename: László
authors.initials: L
authors.lastname: Szereday
authors.forename: Péter
authors.initials: P
authors.lastname: Kisfali
authors.forename: Béla
authors.initials: B
authors.lastname: Melegh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D024921:Drug Resistance, Multiple, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D006801:Humans; D006814:Hungary; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D053701:Receptors, Interleukin-10 / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a