SLC29A1 706G>C predict haemoglobin decrease in patients with hepatitisC treated with interferon and ribavirin
Abstract number: P1142
D'Avolio A., Siccardi M., Ciancio A., Baietto L., Simiele M., Patanella S., Aguilar Marucco D., Cariti G., Calcagno A., Sciandra M., Smedile A., De Rosa F.G., Bonora S., Rizzetto M., Di Perri G.
Objective: Ribavirin (RBV) and pegylated interferon are the standard of treatment in chornic hepatitis C. RBV plasma exposure correlates with the achievement of sustained virological response and hematological toxicity. The role of the equilibrative nucleoside transporter 1 (ENT1), encoded by SLC29A1 gene, in the absorption, transport, metabolism and erythrocyte disposition of RBV has been recently reported. The objective of our investigation was to illustrate whether SNP -706G>C in this gene has an effect on the hematological toxicity and its possible role as a predictor of haemoglobin decrease.
Methods: Patients were recruited in Amedeo di Savoia Hospital and Molinette Hospital in Turin, Italy. Sampling was performed after written informed consent was obtained in accordance with local ethics committee indications. Patients receiving RBV (1000 mg/die) and pegylated interferon therapy were included in this study. Main inclusion criteria were: no concomitant interacting drugs, no renal function impairment, self-reported adherence >95%. Genotyping was conducted by real time PCR based allelic discrimination using standard methodology. Statistical analysis was conducted by SPSS software.
Results: 34 patients were included in the study meeting the inclusion criteria. No associations between patient demographics with ENT1 polymorphism were found. After 2 and 3 months of treatment with RBV the median haemoglobin decrease, expressed as g/dL, in patients with the mutant allele (GC or CC, n = 8) for SNP -706G>C was higher compared to patients with wild-type genotype (GG, n = 26); after 2 months: -4.00 (-4.57 to -2.90) Vs. -2.45 (-3.22 to -1.60), p = 0.017; and after 3 months: -3.90 (-4.82 to -2.95) Vs. -2.7 (-3.50 to -1.66), p = 0.031; In multivariate linear regressions analyses the presence of the mutant allele was the only independent predictor of higher decrease of haemoglobin after 2 (b = -1.13, 95% CI -2.04 to -0.23, p = 0.016) and 3 months (b = -1.05, 95% CI -2.00 to -0.10, p = 0.032).
Conclusions: The mutant allele C correlates with an higher decrease of haemoglobin after 2 and 3 months of treatment. This result suggests that hENT1706G>C may have an important influence on RBV-induced anemia. Further studies are required to confirm this association and to clarify its clinical value in predicting RBV-associated hematological toxicity.
hENT1 and Hb after 2 months of ribavirin treatment.
|Session name:||Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Vienna, Austria, 10 - 13 April 2010|
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