title: Impact of IL28B andOASgene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus.
abstract: OBJECTIVE
  To investigate the impact of IL28B andOASgene polymorphisms on interferon treatment responses in children with chronic hepatitis B.
  
  
  METHODS
  We enrolled 52 children (between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B (CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1 (rs1131476), OAS2 (rs1293747), OAS3 (rs2072136), OASL (rs10849829) and IL28B (rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus (HBV) DNA level < 2000 IU/mL and normalization of ALT activity (< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response (PR) and a complete response (CR) upon measurement at the 24-wk post-treatment follow-up.
  
  
  RESULTS
  The PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response (partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown (P< 0.05). The allele association analysis revealed that only the IL-28B rs12979860 (CvsT) and IL28B rs12980275 (AvsG) markers significantly affected the achievement of PR (P= 0.021, OR = 3.3, 95%CI: 1.2-9.2 andP= 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28B rs12980275 was significantly associated with PR (AAvsAG-GG,P= 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28B rs12979860 was present only in the no-CR group (P= 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the no-CR group (P= 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype (P= 0.0002 andP= 0.001, respectively), but no association with IL28B haplotype was observed.
  
  
  CONCLUSIONS
  IL28B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.
authors.affiliation: Krzysztof Domagalski, Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Toruń, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Domagalski
authors.affiliation: Krzysztof Domagalski, Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Toruń, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Pawłowska
authors.affiliation: Krzysztof Domagalski, Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Toruń, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zaleśna
authors.affiliation: Krzysztof Domagalski, Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Toruń, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Pilarczyk
authors.affiliation: Krzysztof Domagalski, Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Toruń, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Rajewski
authors.affiliation: Krzysztof Domagalski, Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Toruń, Poland.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Halota
authors.affiliation: Krzysztof Domagalski, Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Toruń, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Tretyn
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D000293:Adolescent; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D005787:Gene Frequency; D006239:Haplotypes; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016015:Logistic Models; D015999:Multivariate Analysis; D016017:Odds Ratio; D000071184:Pharmacogenomic Variants; D011044:Poland / Q000453:epidemiology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D000072230:Sustained Virologic Response; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D044465:White People / Q000235:genetics*; D000095022:Interferon Lambda
chemical_list: D015088:2',5'-Oligoadenylate Synthetase; D000410:Alanine Transaminase; D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a
keywords: Children; Chronic hepatitis B; IFN therapy; IL28B; OAS; Single-nucleotide polymorphisms