title: Common genetic polymorphism of ITPA gene affects ribavirin-induced anemia and effect of peg-interferon plus ribavirin therapy.
abstract: An association between a single nucleotide polymorphism (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene and reduction of hemoglobin during peg-interferon plus ribavirin combination therapy for patients with chronic hepatitis C virus (HCV) infection has been reported. However, the effect of the SNP on outcome of therapy has not been fully elucidated. Factors associated with anemia during combination therapy, including rs1127354 genotype, were analyzed in 1,002 treated patients. The effect of the SNP on outcome of therapy was analyzed in a subset of 830 patients with genotype 1. A rapid initial decrease in hemoglobin levels was observed in patients with rs1127354 genotype CC compared with a slow decrease in non-CC patients. Cumulative reduction of ribavirin was significantly more frequent in genotype CC patients than non-CC patients (odds ratio 1.928, P = 8.6 × 10(-8) ). The frequency of patients who received at least the recommended 80% of scheduled ribavirin was significantly lower among genotype CC patients, especially among those who had pretreatment hemoglobin levels between 13.5 and 15 g/dl (P < 0.03), and the sustained viral response rate was significantly lower in this group of patients. Independent predictive factors for sustained virological response included a SNP in the IL28B locus (rs809991), age, fibrosis, ITPA SNP rs1127354 as well as pretreatment hemoglobin levels. Our data suggests that measures to prevent anemia should be considered for patients who have pretreatment hemoglobin levels less than 13.5 g/dl or who have rs1127354 genotype CC and pretreatment hemoglobin levels between 13.5 and 15 g/dl.
authors.affiliation: Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Azakami
authors.forename: C Nelson
authors.initials: CN
authors.lastname: Hayes
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.forename: Yoshiiku
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Shoichi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D019943:Amino Acid Substitution; D000740:Anemia / Q000139:chemically induced* / Q000235:genetics / Q000517:prevention & control; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000032:analysis / Q000378:metabolism; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011755:Pyrophosphatases / Q000235:genetics*; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D016898:Interferon-alpha; D011755:Pyrophosphatases; D012367:RNA, Viral; D012254:Ribavirin; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase