The Association between Single-Nucleotide Polymorphisms in the Inosine Triphosphate Pyrophosphatase Gene and Ribavirin-Induced Hemolytic Anemia in Genotype 2 Hepatitis C Virus-Infected Taiwanese Patients Receiving Pegylated Interferon and Ribavirin Combination Therapy

Background: Genome-wide association studies have reported a significant association between single-nucleotide polymorphisms (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene and ribavirin (RBV)-induced anemia in hepatitis C virus (HCV)-infected patients receiving pegylated interferon (pegIFN) and RBV combination therapy. However, few studies have analyzed genotype 2 HCV (HCV-2)-infected Taiwanese patients.This study aimed to evaluate the effects of these polymorphisms on anemia, hemoglobin (Hb) decline, and treatment outcomes.Materials and Methods: Two hundred and thirty-five eligible HCV-2 infected Taiwanese participants received 24 weeks of therapy. Genomic DNA from peripheral blood mononuclear cells was genotyped for one functional ITPA variant on chromosome 20 (C/C, A/A or C/A, rs1127354). Predictors of severe anemia (Hb ＜ 10 g/dL) and Hb decline (≧ 4 g/dL) were identified. Odds ratios (OR) and hazards ratios (HR) were determined based on a 95% confidence interval (CI).Results: Multivariate logistic regressions identified age (≧ 60 years) (OR, 2.337; CI, 1.180-4.627; P = 0.015), female gender (OR, 3.463; CI, 1.913-6.269; P ＜ 0.001), and ITPA rs1127354 C/C (OR, 2.227; CI, 1.168-4.247; P = 0.015) as predictors of severe anemia throughout treatment. Male gender (OR, 2.224; CI, 1.275-3.879; P = 0.005) and ITPA rs1127354 C/C (OR, 3.135; CI, 1.702-5.775; P ＜ 0.001) were associated with Hb decline. Multivariate Cox regression analysis also identified age (≧60 years) (HR, 1.915; CI, 1.226-2.993; P = 0.004), female gender (HR, 2.712; CI, 1.680-4.380; P ＜ 0.001), and ITPA rs1127354 C/C (HR, 2.162; CI, 1.302-3.590; P = 0.003) as predictors of severe anemia. Sustained virological response (SVR) was not associated with anemia or ITPA SNP.Conclusions: In HCV-2 infected Taiwanese patients on combination therapy, ITPA SNP predicts RBV-induced hemolytic anemia, Hb decline, but does not affect the SVR.