title: Effect of gender and ITPA polymorphisms on ribavirin-induced anemia in chronic hepatitis C patients.
abstract: OBJECTIVE
  Single nucleotide polymorphisms (SNPs) in the inosine triphosphate pyrophosphatase (ITPA) gene protect patients from ribavirin induced anemia. To investigate other possible protective cofactors, gender differences were analyzed in patients with HCV genotype 1.
  
  
  METHODS
  Hemoglobin levels at baseline (Hb0) and the decline after 4 weeks of treatment (HbΔ4) were analyzed in 308 chronic hepatitis C patients participating in 5 Austrian trials (n=308, age 43.9 ± 11.1, male:185, female:123, BMI 25.3 ± 3.9, no cirrhosis: n=259, liver cirrhosis: n=49). All patients were treated with 180 μg peginterferon-alpha 2a and ribavirin [1000-1200 mg/d; females: mean (95% CI) 15.8 mg/kg (15.4-16.2); males 14.3 (14.1-14.5); p<0.001]. The SNPs rs6051702, rs1127354, rs7270101 and IL28B rs12979860 were analyzed by the StepOnePlus Real time PCR System.
  
  
  RESULTS
  188 were major alleles homozygotes; 95 (30.8%) carried the minor allele (C) of rs6051702, 47 (15.3%) of rs1127354 (A), and 69 (22.4%) of rs7270101 (C). The overall Hb0 was 14.8 g/dl (14.6-14.9) [mean (95%CI); females 13.7 (13.5-13.9); males 15.5; 15.3-15.6; p<0.001]. The overall HbΔ4 was greater in major allele homozygotes [2.8 g/dl (2.6-3.0)] than in minor allele carriers [1.6 (1.4-1.9); p<0.001]. Irrespective of the ITPA genotypes HbΔ4 was smaller in female [2.0 (1.7-2.2)] than in male patients [2.6 (2.4-2.8); p<0.001] and among females in premenopausal [1.5 (1.3-1.8)] than in postmenopausal patients [2.7 (2.3-3.1); p<0.001].
  
  
  CONCLUSIONS
  Irrespective of the protective effect of ITPA mutations, premenopausal females less likely develop ribavirin induced anemia.
authors.affiliation: Department of Internal Medicine III, Medical University, Vienna, Austria.
authors.forename: Thomas-Matthias
authors.initials: TM
authors.lastname: Scherzer
authors.forename: Albert Friedrich
authors.initials: AF
authors.lastname: Stättermayer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stauber
authors.forename: Andreas
authors.initials: A
authors.lastname: Maieron
authors.forename: Michael
authors.initials: M
authors.lastname: Strasser
authors.forename: Hermann
authors.initials: H
authors.lastname: Laferl
authors.forename: Remy
authors.initials: R
authors.lastname: Schwarzer
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
authors.forename: Karoline
authors.initials: K
authors.lastname: Rutter
authors.forename: Sandra
authors.initials: S
authors.lastname: Beinhardt
authors.forename: Petra
authors.initials: P
authors.lastname: Steindl-Munda
authors.forename: Harald
authors.initials: H
authors.lastname: Hofer
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
mesh_terms: D000328:Adult; D000483:Alleles; D000740:Anemia / Q000139:chemically induced*; D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006720:Homozygote; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017697:Premenopause / Q000502:physiology; D011755:Pyrophosphatases / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use*; D012737:Sex Factors; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D012254:Ribavirin; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase; C100416:peginterferon alfa-2a
keywords: Age; GWAS; Gender; HCV; Hepatitis C virus; ITPA; RVR; Ribavirin-induced anemia; SNP; SVR; genome-wide association study; rapid virologic response; single nucleotide polymorphism; sustained virologic response