5489
Ahmed Mohamed Hussein Ahmed Heiba
Influence of Single Nucleotide Polymorphism “rs760370” at the Main Ribavirin Transporter Gene on the Early/Sustained Virological Response to Pegylated Interferon–Ribavirin Therapy in Chronic HCV Infection
HCV , Ribavirin , rs760370 SNP , Treatment response, Anaemia , ALT
Background/Aims: Ribavirin clearly plays a role in the HCV treatment response. Ribavirin is primarily transported by the equilibrative nucleoside transporter-1 (ENT1) codified by SLC29A1 gene. rs760370 polymorphism at the SLC29A1 gene was suggested to influence ribavirin activity as part of HCV therapy. Methods: A cross-sectional cohort study was conducted in 100 chronic hepatitis C infected patients who had received pegylated interferon (peg-IFN) / ribavirin. The patients were categorized as early virological responders ending with sustained virological response (EVR/SVR-50 patients) or null-responders (NR-50 patients). rs760370 single nucleotide polymorphism (SNP) at the SLC29A1 gene was examined using TaqMan 5-nuclease assay and also using our newly experimentally designed PCR-based RFLP assay. Results: Allelic frequencies at rs760370 were as follows: A/A genotype (28%), A/G genotype (58%) and G/G genotype (14%) in the studied 100 patients. No association was observed between the 2 groups (NR or EVR/SVR) concerning rs760370 polymorphism (p=0.5). Significant univariate association was found between EVR/SVR as related to basal activity grade (p=0.037) and to on-treatment decline in platelets till 12th ws of therapy (p=0.006). Multivariate logistic regression model conducted to predict responsiveness to Peg-INF/RBV (EVR/SVR) showed that baseline platelet count at cutoff value of 130 x103/mm3 (p=0.03), ALT level at 12 weeks of therapy (p=0.027) and hemoglobin reduction ˂10g/dl within the first 12 weeks of therapy (p= 0.02) were significant. The statistical significance of this model is indicating that the 3 predictors as a set reliably distinguished between SVR and Non-responders (X2 = 23.379, p = 0.00003), with predictive values of 90.9% for SVR and 58.8% for non-response to therapy. Conclusion: rs760370 SNP at the ENT1 gene does not predict the response to peg-IFN/ ribavirin therapy in patients with chronic HCV infection. However, baseline platelet level, ontreatment hemoglobin reduction ˂10g/dl and ALT levels within the first 12 weeks of therapy are good predictors for treatment response. Additionally, the newly designed PCR-based RFLP assay was successfully tested to detect the rs760370 SNP.
2015
M.D
Cairo
Medicine