SLC29A1 polymorphism and prediction of anaemia severity in patients with chronic hepatitis C receiving triple therapy with telaprevir. (11th January 2015)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 70:Number 4(2015:Apr.)
• Page Start: 1155
• Page End: 1160
• Publication Date: 2015-01-11
• Subjects: HCV -- ribavirin -- nucleoside transporters -- single nucleotide polymorphisms; Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dku519
• Languages: English
• ISSNs: 0305-7453

Abstract

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.