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 [-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.

SLC29A1 polymorphism and prediction of anaemia severity in patients with chronic hepatitis C receiving triple therapy with telaprevir / L. Milazzo, A.M. Peri, C. Mazzali, C. Magni, E. Calvi, A. De Nicolò, E. Clementi, S. Cheli, A. D'Avolio, S. Antinori, F.S. Falvella. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 1460-2091. - 70:4(2015 Apr), pp. 1155-1160.

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

A.M. Peri;C. Mazzali;E. Calvi;E. Clementi;S. Cheli;S. Antinori;F.S. Falvella
2015-04

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 [-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.
HCV; nucleoside transporters; ribavirin; single nucleotide polymorphisms
Settore MED/17 - Malattie Infettive
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/272888
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