Background
The non-functional ITPArs6051702 gene polymorphism was associated with ribavirin (RBV)-induced reduction in hemoglobin in some populations (1,2). We explored for the first time the relationship between this non-functional variant in addition to the known functional rs1127354 and rs7270101 ones, and the reduction in hematological parameters: hemoglobin, white blood cells (WBCs) and platelets in Egyptian hepatitis patients treated with RBV.
Materials and Methods
Hundred and twenty-three patients treated with pegylated-interferon (peg-IFN) alpha and RBV have been enrolled. DNA was extracted from buffy coat using Qiagen DNA extraction kits; allelic discrimination was performed for ITPArs6051702, rs1127354 and rs7270101 polymorphisms through real time PCR. Evaluated clinical features were delta hemoglobin, WBCs and platelets reductions at 1, 2, 4, 8 and 12 weeks of therapy.
Results
We found that the genotypes AC/CC for rs6051702 at week 4 and CA/AA for rs1127354 at week 8 were associated with lower hemoglobin reduction (p = 0.012 and p = 0.019, respectively). Association was found between the presence of at least one variant allele of rs1127354 and less WBCs reduction at week 1 and week 4 (p = 0.038 and 0.020 respectively). Less WBCs reduction at week 1 in AA/AC genotypes of rs7270101 (p = 0.025) has been observed. Multivariate linear regression analysis has been done to detect factors independently associated with hemoglobin reduction at weeks 4, 8 and 12. RBV dose (p = 0.017) and ITPArs6051702 (p = 0.028) were independently associated with hemoglobin reduction at week 4. CA/AA group for rs1127354 (p = 0.005), peg-IFN dose (p = 0.033) and sex (p = 0.036) were independent predictors at week 8. Peg-IFN type (p = 0.001) was the independent predictor at week 12.
Conclusions
Genotyping of ITPA variants rs6051702 and rs1127354 could be performed to predict anemia before the start of treatment in Egyptian patients.
References
1. Fellay J, Thompson J, Ge D, et al. ITPA gene variants protect against anemia in patients treated for chronic hepatitis C. Nature 2010, 464, 405–8.
2. Sakamoto N, Tanaka Y, Nakagawa M, et al. ITPA gene variant protects against anemia induced by pegylated interferon-alpha and ribavirin therapy for Japanese patients with chronic hepatitis C. Hepatology Research 2010,40, 1063–71.
