title: Association of interferon-gamma inducible protein 10 polymorphism with treatment response to pegylated interferon in HBeAg-positive chronic hepatitis B.
abstract: Interferon-gamma inducible protein 10 (IP-10) plays an important role in the clinical outcome of chronic hepatitis B (CHB). This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) G-201A of the IP-10 gene and treatment response to pegylated interferon (PEG-IFN) in patients with hepatitis B e antigen (HBeAg)-positive CHB.
  
  
  
  We retrospectively analysed data of patients with HBeAg-positive CHB treated with PEG-IFN for 48 weeks. Virological response (VR) was defined as HBeAg clearance and HBV DNA <2,000 IU/ml at 24 weeks post-treatment. The SNPs G-201A, IFNL3 (rs12979860) and HLA-DPA1 (rs3077) were assessed.
  
  
  
  Among 107 patients, VR was achieved in 45 (42.1%) patients. Hepatitis B surface antigen (HBsAg) clearance and decline (<100 IU/ml) were observed in 10 (9.3%) and 22 (20.6%) patients, respectively. The distribution of GG, GA and AA genotypes of G-201A was 76.6%, 19.6% and 3.7%, respectively. Patients with GG genotype, compared to those with non-GG genotype, achieved higher VR rate (48.8% versus 19.2%; P=0.011), decreased HBsAg (25.6% versus 4.0%; P=0.019), and demonstrated a trend in HBsAg clearance (11.0% versus 4%; P=0.294). Patients with GG genotype had more rapid HBsAg decline and higher baseline serum IP-10 levels than those with non-GG genotype (432.2 ±339.0 versus 257.3 ±145.7 pg/ml; P=0.028). SNPs rs12979860 and rs3077 were not associated with VR. Logistic regression analysis suggested that SNP G-201A was an independent predictor of VR (odds ratio 3.81, 95% CI 1.31, 11.12; P=0.014).
  
  
  
  Data from this study demonstrated for the first time that IP-10 polymorphism is independently associated with treatment response to PEG-IFN in patients with HBeAg-positive CHB.
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Umaporn
authors.initials: U
authors.lastname: Limothai
authors.forename: Natthaya
authors.initials: N
authors.lastname: Chuaypen
authors.forename: Apichaya
authors.initials: A
authors.lastname: Khlaiphuengsin
authors.forename: Nawarat
authors.initials: N
authors.lastname: Posuwan
authors.forename: Rujipat
authors.initials: R
authors.lastname: Wasitthankasem
authors.forename: Yong
authors.initials: Y
authors.lastname: Poovorawan
authors.forename: Pisit
authors.initials: P
authors.lastname: Tangkijvanich
mesh_terms: D000328:Adult; D054357:Chemokine CXCL10 / Q000235:genetics*; D004279:DNA, Viral; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006513:Hepatitis B e Antigens; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a