title: Pre-treatment role of inosine triphosphate pyrophosphatase polymorphism for predicting anemia in Egyptian hepatitis C virus patients.
abstract: OBJECTIVE
  To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA) polymorphism in Egyptian chronic hepatitis C virus (HCV) patients.
  
  
  METHODS
  The human genomic DNA of all patients was extracted from peripheral blood cells in order to determine the single nucleotide polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102 treatment-naive Egyptian patients with chronic HCV. All patients had no evidence of cardiovascular or renal diseases. They received a combination treatment of pegylated interferon α (PEG-IFNα) as a weekly subcutaneous dose plus an oral weight-adjusted dose of ribavirin (RBV). The majority received PEG-IFNα2a (70.6%) while 29.4% received PEG-IFNα2b. The planned duration of treatment was 24-48 wk according to the viral kinetics throughout the course of treatment. Pre-treatment liver biopsy was done for each patient for evaluation of fibrosis stage and liver disease activity. The basal viral load level was detected quantitatively by real time PCR while viral load throughout the treatment course was performed qualitatively by COBAS TaqMan assay.
  
  
  RESULTS
  Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC patients than for non-CC patients, particularly at weeks 4 and 8 (P = 0.047 and 0.034, respectively). During the first 12 wk of treatment, CC patients had significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at weeks 8 and 12, respectively, (P = 0.024 and 0.038). Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P = 0.021). The percentage of CC patients with RBV dose reduction was significantly greater than that of non-CC patients (77.4% vs 44.4%, P = 0.044). Multivariate analysis identified only the percentage of RBV dose as a predictor for Hb decline. Platelet decline was significantly higher in non-CC patients than CC patients at weeks 12, 24 and 48 (P = 0.018, 0.009 and 0.026, respectively).
  
  
  CONCLUSIONS
  Rs1127354 ITPA polymorphism plays a decisive role in protecting against treatment-induced anemia and the need for RBV dose reduction in Egyptian HCV patients.
authors.affiliation: Department of Environmental Medicine and Infectious Diseases, Kyushu University Hospital, Fukuoka 812-8582, Japan.
authors.forename: Walaa H
authors.initials: WH
authors.lastname: Ahmed
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.forename: Saad
authors.initials: S
authors.lastname: Zaky
authors.forename: Abeer Sharaf
authors.initials: AS
authors.lastname: Eldin
authors.forename: Hany
authors.initials: H
authors.lastname: Aboalam
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ogawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Murata
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000740:Anemia / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D000998:Antiviral Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D004534:Egypt / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006454:Hemoglobins / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D011092:Polyethylene Glycols / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D011994:Recombinant Proteins / Q000009:adverse effects; D012254:Ribavirin / Q000009:adverse effects*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; 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; C100416:peginterferon alfa-2a
keywords: Anemia; Dose reduction; Hepatitis C; Inosine triphosphate; Ribavirin; Rs1127354
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