title: IL28B polymorphisms and clinical implications for hepatitis C virus infection in Uzbekistan.
abstract: OBJECTIVE
  Genome-wide association studies highlighted single nucleotide polymorphisms (SNPs) within the IFNL3/IL28B locus predict the treatment outcome for patients with HCV. Furthermore, SNPs in newly discovered IFNL4 are shown to have population-specific correlation with spontaneous clearance of HCV. The aim of this study was to examine the prevalence and clinical significance of the outlined SNPs in a population from Central Asia, a multi-ethnic region with a developing economy and a high prevalence of HCV infection.
  
  
  METHODS
  One hundred and thirty-five chronic HCV patients from Uzbekistan were enrolled. DNA specimens were extracted from peripheral blood mononuclear cells and the IFNL3 SNPs (rs8099917, rs12979860) were genotyped by the Invader Plus assay, the TaqMan assay, and by direct sequence analysis. The IFL4 region (ss469415590) was sequenced.
  
  
  RESULTS
  Of the 135 patients that completed 24 or 48 weeks of treatment with Peg-IFN-α plus RBV, 87.4% were of Central Asian (CA) ancestry and 12.6% were of Eastern European (EE) ancestry. A non-virological response was observed in 21.2% of CA and in 35.3% of EE, respectively (p<0.32). The rs12979860 was strongly associated with treatment response (OR, 5.2; 95% CI, 1.9-14.6; p<0.004) in the overall sample; however, SNP rs8099917 was the most predictive of outcome for CA group (OR, 6.9; 95% CI, 2.6-18.0; p<0.002). The allele frequency of IFNL4 SNP, ss469415590, was identical with that of rs12979860 in all samples.
  
  
  CONCLUSIONS
  SNPs in IFNL3 and IFNL4 can be used to predict HCV treatment outcome in a population of Central Asian ancestry.
authors.affiliation: Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan; Institute of Virology, Ministry of Public Health of Uzbekistan, Tashkent, Uzbekistan.
authors.forename: Dinara
authors.initials: D
authors.lastname: Khudayberganova
authors.affiliation: Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Masaki
authors.affiliation: Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Motokazu
authors.initials: M
authors.lastname: Mukaide
authors.affiliation: Institute of Virology, Ministry of Public Health of Uzbekistan, Tashkent, Uzbekistan.
authors.forename: Dildora
authors.initials: D
authors.lastname: Sekler
authors.affiliation: Institute of Virology, Ministry of Public Health of Uzbekistan, Tashkent, Uzbekistan.
authors.forename: Renat
authors.initials: R
authors.lastname: Latipov
authors.affiliation: Institute of Virology, Ministry of Public Health of Uzbekistan, Tashkent, Uzbekistan.
authors.forename: Kan
authors.initials: K
authors.lastname: Nataliya
authors.affiliation: Institute of Virology, Ministry of Public Health of Uzbekistan, Tashkent, Uzbekistan.
authors.forename: Suyarkulova
authors.initials: S
authors.lastname: Dildora
authors.affiliation: Institute of Virology, Ministry of Public Health of Uzbekistan, Tashkent, Uzbekistan.
authors.forename: Said
authors.initials: S
authors.lastname: Sharapov
authors.affiliation: Institute of Virology, Ministry of Public Health of Uzbekistan, Tashkent, Uzbekistan.
authors.forename: Guzal
authors.initials: G
authors.lastname: Usmanova
authors.affiliation: Institute of Virology, Ministry of Public Health of Uzbekistan, Tashkent, Uzbekistan.
authors.forename: Mahmarajab
authors.initials: M
authors.lastname: Raxmanov
authors.affiliation: Institute of Virology, Ministry of Public Health of Uzbekistan, Tashkent, Uzbekistan.
authors.forename: Erkin
authors.initials: E
authors.lastname: Musabaev
authors.affiliation: Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D044466:Asian People; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014610:Uzbekistan / Q000453:epidemiology; D044465:White People; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda