title: SLC29A1 polymorphism and prediction of anaemia severity in patients with chronic hepatitis C receiving triple therapy with telaprevir.
abstract: OBJECTIVE
  The equilibrative nucleoside transporter 1 (ENT1) is the main protein involved in ribavirin cellular uptake. Polymorphisms at the SLC29A1 gene, encoding ENT1, may influence ribavirin-associated anaemia, which is observed at a higher incidence with telaprevir in combination with pegylated-IFNα and ribavirin than with pegylated-IFNα and ribavirin alone. In this study, we investigated the role of the rs760370 SLC29A1 variant in ribavirin-induced anaemia in chronic hepatitis C patients treated with telaprevir-based triple therapy.
  
  
  METHODS
  Forty patients infected with hepatitis C virus (HCV) genotype 1 and starting anti-HCV therapy with telaprevir in combination with pegylated-IFN/ribavirin were prospectively evaluated for SNPs at the SLC29A1 gene and inosine triphosphatase (ITPA) genes using a real-time PCR system.
  
  
  RESULTS
  40% of patients developed severe anaemia with a haemoglobin (Hb) decline ≥ 5 g/dL from the pretreatment value. The SLC29A1 rs760370 GG genotype was associated with the severity of Hb decrease as expressed by the median (IQR) Hb nadir change from baseline [-5.4 (-5.6; -5.0) g/dL in GG versus -4.2 (-5.1; -3.4) in AA/AG genotype; P=0.05] and by the Hb decrease ≥ 5 g/dL by week 12 (77.8% of GG carriers versus 24% of AA/AG; P<0.01). In multivariate analysis, older age (P=0.03), lower baseline Hb concentration (P=0.02) and SLC29A1 rs760370 GG (P=0.02) were associated with the development of severe anaemia during treatment, whereas no association was found with ITPA SNPs in our population receiving telaprevir-based therapy.
  
  
  CONCLUSIONS
  In patients with chronic hepatitis C receiving telaprevir-based therapy, SNP rs760370A>G at the SLC29A1 gene influences the severity of ribavirin-induced anaemia, possibly mirroring the erythrocyte uptake of ribavirin.
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy laura.milazzo@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Milazzo
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Peri
authors.affiliation: Department of Clinical Sciences, Section of Biostatistics, University of Milan, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mazzali
authors.affiliation: I Division of Infectious Diseases, Luigi Sacco Hospital, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Magni
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Calvi
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: De Nicolò
authors.affiliation: Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Milan, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Clementi
authors.affiliation: Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Cheli
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy.
authors.forename: Spinello
authors.initials: S
authors.lastname: Antinori
authors.affiliation: Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Milan, Italy.
authors.forename: Felicia Stefania
authors.initials: FS
authors.lastname: Falvella
mesh_terms: D000740:Anemia / Q000139:chemically induced* / Q000453:epidemiology*; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D033721:Equilibrative Nucleoside Transporter 1; D016898:Interferon-alpha; D009842:Oligopeptides; C438649:SLC29A1 protein, human; D012254:Ribavirin; C486464:telaprevir
keywords: HCV; nucleoside transporters; ribavirin; single nucleotide polymorphisms