title: Association of ITPA polymorphism with outcomes of peginterferon-α plus ribavirin combination therapy.
abstract: OBJECTIVE
  To analyzed the association between inosine triphosphatase (ITPA) (rs1127354) genotypes and sustained virological response (SVR) rates in peginterferon (Peg-IFN)α + ribavirin (RBV) treatment.
  
  
  METHODS
  Patients who underwent Peg-IFNα + RBV combination therapy were enrolled (n = 120) and they had no history of other IFN-based treatments. Variation in hemoglobin levels during therapy, cumulative reduction of RBV dose, frequency of treatment withdrawal, and SVR rates were investigated in each ITPA genotype.
  
  
  RESULTS
  In patients with ITPA CC genotype, hemoglobin decline was significantly greater and the percentage of patients in whom total RBV dose was < 60% of standard and/or treatment was withdrawn was significantly higher compared with CA/AA genotype. However, SVR rates were equivalent between CC and CA/AA genotypes, and within a subset of patients with Interleukin 28B (IL28B) (rs8099917) TT genotype, SVR rates tended to be higher in patients with ITPA CC genotype, although the difference was not significant.
  
  
  CONCLUSIONS
  ITPA CC genotype was a disadvantageous factor for Peg-IFNα + RBV treatment in relation to completion rates and RBV dose. However, CC genotype was not inferior to CA/AA genotype for SVR rates. When full-length treatment is accomplished, it is plausible that more SVR is achieved in patients with ITPA CC variant, especially in a background of IL28B TT genotype.
authors.affiliation: Tatsuya Fujino, Laboratory for Clinical Investigation, National Hospital Organization Nagasaki Medical Center, Ohmura, Nagasaki 856-8562, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujino
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Mariko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yada
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohishi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nishiura
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Kunitaka
authors.initials: K
authors.lastname: Fukuizumi
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakashima
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
keywords: Chronic hepatitis C; Inosine triphosphatase; Interleukin 28B; Peginterferon; Ribavirin
references.citation: J Gastroenterol. 2012 May;47(5):596-605
references.pmid: 22438096
references.citation: Hepatol Res. 2003 Apr;25(4):409-414
references.pmid: 12699851
references.citation: Nature. 2009 Sep 17;461(7262):399-401
references.pmid: 19684573
references.citation: Best Pract Res Clin Gastroenterol. 2012 Aug;26(4):413-27
references.pmid: 23199501
references.citation: Hepatology. 2000 Apr;31(4):997-1004
references.pmid: 10733558
references.citation: N Engl J Med. 2009 Apr 30;360(18):1839-50
references.pmid: 19403903
references.citation: N Engl J Med. 2009 Apr 30;360(18):1827-38
references.pmid: 19403902
references.citation: Ann Intern Med. 2004 Mar 2;140(5):346-55
references.pmid: 14996676
references.citation: Hepatol Res. 2010 Nov;40(11):1063-71
references.pmid: 20977565
references.citation: Biochem Biophys Res Commun. 1990 Aug 16;170(3):1021-5
references.pmid: 2117923
references.citation: J Med Virol. 2011 Jun;83(6):1048-57
references.pmid: 21503919
references.citation: J Med Virol. 2012 Jul;84(7):1106-14
references.pmid: 22585729
references.citation: J Hum Genet. 2002;47(11):620-2
references.pmid: 12436200
references.citation: Hepatology. 2011 Feb;53(2):389-95
references.pmid: 21274861
references.citation: Hum Mol Genet. 2011 Sep 1;20(17):3507-16
references.pmid: 21659334
references.citation: J Mol Biol. 2009 Sep 25;392(3):602-13
references.pmid: 19631656
references.citation: Gastroenterology. 2011 Apr;140(4):1314-21
references.pmid: 21199653
references.citation: Nat Genet. 2009 Oct;41(10):1100-4
references.pmid: 19749758
references.citation: Curr Med Chem. 2006;13(27):3351-7
references.pmid: 17168855
references.citation: Nature. 2010 Mar 18;464(7287):405-8
references.pmid: 20173735
references.citation: Hum Genet. 2002 Oct;111(4-5):360-7
references.pmid: 12384777
references.citation: Eur J Gastroenterol Hepatol. 2012 Aug;24(8):890-6
references.pmid: 22584257
references.citation: Gastroenterology. 2010 Oct;139(4):1181-9
references.pmid: 20547162
references.citation: Lancet. 2001 Sep 22;358(9286):958-65
references.pmid: 11583749
references.citation: Biochim Biophys Acta. 2007 Jan;1772(1):96-102
references.pmid: 17113761
references.citation: Hepatology. 2011 Feb;53(2):415-21
references.pmid: 21246582
references.citation: N Engl J Med. 2002 Sep 26;347(13):975-82
references.pmid: 12324553
references.citation: Gastroenterology. 2010 Oct;139(4):1190-7
references.pmid: 20637204
references.citation: J Med Virol. 2012 Jul;84(7):1097-105
references.pmid: 22585728
references.citation: Nat Genet. 2009 Oct;41(10):1105-9
references.pmid: 19749757