title: Association of IPS1 polymorphisms with peginterferon efficacy in chronic hepatitis B with HBeAg-positive in the Chinese population.
abstract: OBJECTIVE
  To investigate whether IPS1 polymorphisms affect peginterferon alpha (PEG-IFN) efficacy in chronic hepatitis B (CHB) patients using a tag- single nucleotide polymorphism (SNP) approach.
  
  
  METHODS
  A total of 212 hepatitis B e antigen (HBeAg)-positive patients treated with a 48weeks of PEG-IFN monotherapy were enrolled initially and 127 patients were followed for 48weeks posttreatment. Genotype analysis was performed for 10 tag-SNPs in IPS1.
  
  
  RESULTS
  The end of virological response (EVR) rate was 45.8% (97/212) and the sustained virological response (SVR) rate was 45.7% (58/127). Meanwhile, 35.4% (75/212) achieved HBeAg seroconversion at the end of treatment. In a multivariate analysis, the rs2464 CC genotype was independently associated with EVR (OR 2.21, 95% CI 1.23-3.98, P=0.008) and SVR (OR 2.34, 95% CI 1.05-5.20, P=0.037) after adjustment for sex, age, HBV genotype, baseline levels of HBV DNA and ALT. Meanwhile, rs2464 CC genotype were also independently associated with decline of HBsAg levels below 1500IU/mL at 12weeks of treatment (OR 2.52, 95% CI 1.01-6.29, P=0.047). Furthermore, three SNPs were found to be independently associated with HBeAg seroconversion at the end of treatment. (1) The rs2326369 CC genotype was independently associated with no HBeAg seroconversion (OR 0.52, 95% CI 0.29-0.95, P=0.034); (2) The rs6515831 TT genotype was independently associated with HBeAg seroconversion (OR 2.11, 95% CI 1.14-3.90, P=0.017); (3) The rs2464 CC genotype was independently associated with HBeAg seroconversion (OR 2.36, 95% CI 1.26-4.42, P=0.007).
  
  
  CONCLUSIONS
  Polymorphisms in IPS1 are independently associated with treatment response to PEG-IFN among Chinese HBeAg-positive CHB patients.
authors: Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: wanghuirj@163.com.
authors: Hui
authors: H
authors: Wang
authors: Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Cardiology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors: Haiqing
authors: H
authors: Wu
authors: Discipline of Pathology, School of Medical Sciences and The Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia.
authors: Shisan
authors: S
authors: Bao
authors: Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Xiaogang
authors: X
authors: Xiang
authors: Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Gangde
authors: G
authors: Zhao
authors: Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Kehui
authors: K
authors: Liu
authors: Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Fengdi
authors: F
authors: Li
authors: Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Yumin
authors: Y
authors: Xu
authors: Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Baoyan
authors: B
authors: An
authors: Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Huijuan
authors: H
authors: Zhou
authors: Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Jie
authors: J
authors: Lu
authors: Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: xieqingrjh@163.com.
authors: Qing
authors: Q
authors: Xie
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002681:China; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D015810:Linkage Disequilibrium; D008297:Male; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000998:Antiviral Agents; D015415:Biomarkers; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; C505371:MAVS protein, human; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a
keywords: Chronic hepatitis B; IPS1; Interferon therapy; Single nucleotide polymorphism