Inosine Triphosphate Pyrophosphatase Gene Polymorphisms and Ribavirin-Induced Anemia in HCV Patients

Abstract

In spite of the interferon (INF) redundancy in treating HCV, ribavirin (RBV) is still included with the new direct antiviral therapies. Ribavirin-induced hematological alterations had been referred to ITPA gene polymorphisms. Objective: Evaluate ITPA gene polymorphisms (rs1127354 and rs7270101) with development of anemia in chronic hepatitis C (CHC) Egyptian patients during treatment with pegylated-interferon (Peg-IFN) plus ribavirin (RBV). Methods: 100 Egyptian CHC patients treated with PEG-IFN/RBV were recruited, 55 patients developed anemia (Hb decline>2 g/dl), and other 45 would not developed anemia (Hb decline ≤ 2 g/dl) at week 12 throughout the treatment course. Routine laboratory investigations were done for all participates (HCV-Abs, HBs Ag, HCV-RNA levels, complete blood picture, liver and kidney function tests. Single nucleotide polymorphism (SNP) was done by ABI TaqMan allelic discrimination kit for ITPA polymorphisms (rs1127354 and rs7270101). Results: CC and AA were the most prevalent genotypes of SNPs rs1127354 and rs7270101 respectively among two studied groups. rs1127354 polymorphism was associated with Hb-decline at week 12 of treatment and with rs7270101 polymorphism for predicting platelet decline during treatment. Lower levels of platelet decline were detected with CC rs1127354 and AA rs7270101. Conclusion: While ITPA polymorphisms rs1127354 CC genotype carried a predilection of anemia occurrence in PEG-IFN/RBV HCV treated subjects, the minor allele rs1127354 AA plays a crucial role in their protection. Platelet decline was reported in both ITPA rs1127354 and rs7270101 polymorphisms. Screening for ITPA polymorphisms in Egyptian HCV patients would be of value in avoiding hematological disturbances and dose modulations in RBVbased therapies.