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 language | English |
|---|---|
| Pages (from-to) | 1155-1160 |
| Number of pages | 6 |
| Journal | Journal of Antimicrobial Chemotherapy |
| Volume | 70 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Sep 16 2014 |
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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 journal › Article
}
TY - JOUR
T1 - SLC29A1 polymorphism and prediction of anaemia severity in patients with chronic hepatitis C receiving triple therapy with telaprevir
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
PY - 2014/9/16
Y1 - 2014/9/16
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.
KW - HCV
KW - Nucleoside transporters
KW - Ribavirin
KW - Single nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=84926505393&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926505393&partnerID=8YFLogxK
U2 - 10.1093/jac/dku519
DO - 10.1093/jac/dku519
M3 - Article
C2 - 25583751
AN - SCOPUS:84926505393
VL - 70
SP - 1155
EP - 1160
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 4
ER -