SLC29A1 polymorphism and prediction of anaemia severity in patients with chronic hepatitis C receiving triple therapy with telaprevir

Laura Milazzo, Anna Maria Peri, Cristina Mazzali, Carlo Magni, Elisa Calvi, Amedeo De Nicolò, Emilio Clementi, Stefania Cheli, Antonio D'Avolio, Spinello Antinori, Felicia Stefania Falvella

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: 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 [25.4 (25.6; 25.0) g/dL in GG versus 24.2 (25.1; 23.4) 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; PG at the SLC29A1 gene influences the severity of ribavirin-induced anaemia, possibly mirroring the erythrocyte uptake of ribavirin.

Original languageEnglish
Pages (from-to)1155-1160
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume70
Issue number4
DOIs
Publication statusPublished - Sep 16 2014

Fingerprint

Ribavirin
Chronic Hepatitis C
Anemia
Equilibrative Nucleoside Transporter 1
Hemoglobins
Genotype
Therapeutics
Hepacivirus
Genes
telaprevir
Computer Systems
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction
Erythrocytes
Incidence

Keywords

  • HCV
  • Nucleoside transporters
  • Ribavirin
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases
  • Medicine(all)

Cite this

SLC29A1 polymorphism and prediction of anaemia severity in patients with chronic hepatitis C receiving triple therapy with telaprevir. / Milazzo, Laura; Peri, Anna Maria; Mazzali, Cristina; Magni, Carlo; Calvi, Elisa; De Nicolò, Amedeo; Clementi, Emilio; Cheli, Stefania; D'Avolio, Antonio; Antinori, Spinello; Falvella, Felicia Stefania.

In: Journal of Antimicrobial Chemotherapy, Vol. 70, No. 4, 16.09.2014, p. 1155-1160.

Research output: Contribution to journalArticle

Milazzo, L, Peri, AM, Mazzali, C, Magni, C, Calvi, E, De Nicolò, A, Clementi, E, Cheli, S, D'Avolio, A, Antinori, S & Falvella, FS 2014, 'SLC29A1 polymorphism and prediction of anaemia severity in patients with chronic hepatitis C receiving triple therapy with telaprevir', Journal of Antimicrobial Chemotherapy, vol. 70, no. 4, pp. 1155-1160. https://doi.org/10.1093/jac/dku519
Milazzo, Laura ; Peri, Anna Maria ; Mazzali, Cristina ; Magni, Carlo ; Calvi, Elisa ; De Nicolò, Amedeo ; Clementi, Emilio ; Cheli, Stefania ; D'Avolio, Antonio ; Antinori, Spinello ; Falvella, Felicia Stefania. / SLC29A1 polymorphism and prediction of anaemia severity in patients with chronic hepatitis C receiving triple therapy with telaprevir. In: Journal of Antimicrobial Chemotherapy. 2014 ; Vol. 70, No. 4. pp. 1155-1160.
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abstract = "Objectives: 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 [25.4 (25.6; 25.0) g/dL in GG versus 24.2 (25.1; 23.4) 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; PG at the SLC29A1 gene influences the severity of ribavirin-induced anaemia, possibly mirroring the erythrocyte uptake of ribavirin.",
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AU - Milazzo, Laura

AU - Peri, Anna Maria

AU - Mazzali, Cristina

AU - Magni, Carlo

AU - Calvi, Elisa

AU - De Nicolò, Amedeo

AU - Clementi, Emilio

AU - Cheli, Stefania

AU - D'Avolio, Antonio

AU - Antinori, Spinello

AU - Falvella, Felicia Stefania

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N2 - Objectives: 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 [25.4 (25.6; 25.0) g/dL in GG versus 24.2 (25.1; 23.4) 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; PG at the SLC29A1 gene influences the severity of ribavirin-induced anaemia, possibly mirroring the erythrocyte uptake of ribavirin.

AB - Objectives: 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 [25.4 (25.6; 25.0) g/dL in GG versus 24.2 (25.1; 23.4) 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; PG at the SLC29A1 gene influences the severity of ribavirin-induced anaemia, possibly mirroring the erythrocyte uptake of ribavirin.

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