title: Polymorphism of the inosine triphosphate pyrophosphatase gene predicts             ribavirin-induced anemia in chronic hepatitis C patients.
abstract: Ribavirin (RBV)-induced anemia is a serious side effect of pegylated interferon (PEG-IFN) plus RBV therapy which is the standard care most effective for hepatitis C virus (HCV) infection. In the present study, we investigated the association of inosine triphosphate pyrophosphatase (ITPA) genotypes with RBV-induced hemoglobin (Hb) reduction in HCV patients treated with PEG-IFN/RBV therapy. The genotypes of the ITPA rs1127354 single nucleotide polymorphism were determined in 179 patients with HCV infection. Among them, 52 patients were treated with PEG-IFN/RBV. The frequency of the ITPA major allele (CC) was 76.3% and that of the minor allele (CA and AA) was 23.7%. A rapid decrease in Hb levels during the initial 4 weeks was observed in patients with the ITPA major allele (CC), but not in patients with the ITPA minor allele (C/A and AA). Hb levels at 4 weeks were significantly lower in patients with the ITPA major allele than the levels in patients with the minor allele. Out of the 41 patients, 6 (14.6%) with ITPA major allele had Hb levels <10 g/dl and 11 patients (26.8%) had a decline in Hb of >3 g/dl. None of the patients with the ITPA minor allele had such data. There were no significant differences in virological responses of HCV-RNA between patients with the ITPA major allele and those with the minor allele. In conclusion, the ITPA genotypes may be a useful marker for prediction of RBV-induced anemia.
authors: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors: Takashi
authors: T
authors: Nishimura
authors: Rie
authors: R
authors: Osaki
authors: Makoto
authors: M
authors: Shioya
authors: Hirotsugu
authors: H
authors: Imaeda
authors: Tomoki
authors: T
authors: Aomatsu
authors: Takayuki
authors: T
authors: Takeuchi
authors: Yoshiaki
authors: Y
authors: Okumura
authors: Yoshihide
authors: Y
authors: Fujiyama
authors: Akira
authors: A
authors: Andoh
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000740:Anemia / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D012703:Serotyping; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D012254:Ribavirin; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase; C417083:peginterferon alfa-2b