title: Association between IPTA gene polymorphisms and hematological abnormalities in hepatitis C virus-infected patients receiving combination therapy.
abstract: OBJECTIVE
  Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon α and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combina-tion treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the as-sociation between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy.
  
  
  METHODS
  In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy.
  
  
  RESULTS
  The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86×10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055).
  
  
  CONCLUSIONS
  The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy. (Gut Liver, 2015;9214-223).
authors.affiliation: Section of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital and Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Chiayi, Taiwan.
authors.forename: Jow Jyh
authors.initials: JJ
authors.lastname: Hwang
authors.affiliation: Section of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan.
authors.forename: Ching Chu
authors.initials: CC
authors.lastname: Lo
authors.affiliation: Section of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan.
authors.forename: Chien Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Section of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan.
authors.forename: Hsu Sheng
authors.initials: HS
authors.lastname: Cheng
authors.affiliation: Outpatient Nursing Section, St. Martin De Porres Hospital, Chiayi, Taiwan.
authors.forename: I Wen
authors.initials: IW
authors.lastname: Hung
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Chiayi, Taiwan.
authors.forename: Wan Ju
authors.initials: WJ
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Chiayi, Taiwan.
authors.forename: Chien Hui
authors.initials: CH
authors.lastname: Hung
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000235:genetics; D000998:Antiviral Agents / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000235:genetics; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D012189:Retrospective Studies; D012254:Ribavirin / Q000009:adverse effects; D013624:Taiwan; D013921:Thrombocytopenia / Q000139:chemically induced / Q000235:genetics; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011755:Pyrophosphatases; D012254:Ribavirin; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase
keywords: Chronic hepatitis C; Hematologic abnormalities; ITPA; Polymorphism; Ribavirin