title: Impact of host IL28B rs12979860, rs8099917 in interferon responsiveness and advanced liver disease in chronic genotype 3 hepatitis C patients.
abstract: OBJECTIVE
  Genetic polymorphisms near interleukin 28B gene are associated with spontaneous and treatment induced clearance of hepatitis C virus (HCV). Our objective was to evaluate the impact of interleukin 28B single nucleotide polymorphism (rs12979860, rs8099917) variability in HCV genotype 3 infected populations.
  
  
  METHODS
  400 hepatitis C seroreactive patients from different population groups in Eastern and North Eastern part of India were assessed for host and viral genotypic analysis. 83 HCV genotype 3 infected patients were administered pegylated interferon- ribavirin therapy. Viral genotyping was performed using nested reverse transcriptase-PCR followed by direct sequencing methods. Host interleukin 28B genotyping was performed using real-time PCR based single nucleotide polymorphism analysis.
  
  
  RESULTS
  Out of 400 hepatitis C seroreactive individuals, 73.25% were found to be RNA positive. HCV genotype 3 (65.87%) was found to be the major circulating strain in this region followed by genotype 1 (32.08%). rs12979860 CC genotype was significantly associated with sustained virological response in HCV genotype 3 infected population. In patients achieving rapid virological response, favourable CC/TT allele at rs12979860, rs8099917 was found to be predominant at both the alleles at 77%, 73.2% respectively; whereas in case of patients with relapsed HCV infection CT, TG alleles were found to be predominant. Additionally, CC genotypes at rs12979860 were found to be associated with sustained virological response in patients with high viral load (OR = 6.75, 0.05<p). HCV unfavourable rs12979860 TT, rs8099917 GG alleles were present in 34%, 27.6% patients with relapsed HCV infection respectively. Also unfavourable CT, TG genotypes were found to be predominant in patients with advanced stages of liver disease.
  
  
  CONCLUSIONS
  CC, TT the two favourable markers at SNPs rs12979860 and rs8099917 are strongly associated with sustained virological response in genotype 3 infected populations. This information will aid clinicians to effectively design response based treatment regimen.
authors.affiliation: I.C.M.R. Virus Unit Kolkata, Indian Council of Medical Research, Kolkata, India.
authors.forename: Rushna
authors.initials: R
authors.lastname: Firdaus
authors.affiliation: I.C.M.R. Virus Unit Kolkata, Indian Council of Medical Research, Kolkata, India.
authors.forename: Aritra
authors.initials: A
authors.lastname: Biswas
authors.affiliation: I.C.M.R. Virus Unit Kolkata, Indian Council of Medical Research, Kolkata, India.
authors.forename: Kallol
authors.initials: K
authors.lastname: Saha
authors.affiliation: I.C.M.R. Virus Unit Kolkata, Indian Council of Medical Research, Kolkata, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Gastroenterology, AMRI Hospitals Salt Lake, Kolkata, India.
authors.forename: Sujit
authors.initials: S
authors.lastname: Chaudhuri
authors.affiliation: Department of Medicine and Gastroenterology, Command Hospital, Kolkata, India.
authors.forename: Alok
authors.initials: A
authors.lastname: Chandra
authors.affiliation: Department of Gastroenterology, Peerless Hospital and B.K. Roy Research Centre, Kolkata, India.
authors.forename: Asokananda
authors.initials: A
authors.lastname: Konar
authors.affiliation: I.C.M.R. Virus Unit Kolkata, Indian Council of Medical Research, Kolkata, India.
authors.forename: Provash Chandra
authors.initials: PC
authors.lastname: Sadhukhan
mesh_terms: D000328:Adult; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D060005:Genotyping Techniques; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000473:pathology* / Q000821:virology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012008:Recurrence; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda