Association of ITPA polymorphisms rs6051702/rs1127354 instead of rs7270101/rs1127354 as predictor of ribavirin-associated anemia in chronic hepatitis C treated patients

Intracellular accumulation of boceprevir according to plasma concentrations and pharmacogenetics

“…The genetics of IL28B and inosine triphosphate pyrophosphohydrolase (ITPA) have played an important role in predicting outcome and toxicity in dual therapy as well as the pharmacokinetics of RBV [7][8][9].…”

Variant Inosine Triphosphatase Phenotypes Are Associated With Increased Ribavirin Triphosphate Levels

“…This observation is also supported by the fact that rs1127354 homozygous variants have the lowest ITPA activity at < 5%. Other studies have also shown that rs7270101 may be less important for anemia protection than other SNPs studied in combination with rs1127354 …”

VDR gene polymorphisms impact on anemia at 2 weeks of anti-HCV therapy

“…RBV frequently induces dosedependent anemia, requiring dose reduction in 22-40% of monoinfected patients and in 50% of coinfected (HIV/HCV) ones [7,8]. Baseline hemoglobin (Hb) level, baseline platelet, female sex, age, dose, RBV plasma concentrations, and the haptoglobin phenotype are factors that contribute toward this side effect and dose reduction [9][10][11]. Erythrocyte hemolysis is considered the main etiology of this kind of anemia [12], but the fine mechanism remains to be elucidated.…”

“…An increase in the ITP concentration may cause a decrease in the phosphate concentration, reducing the conversion of RBV into RBV-triphosphate and, consequently, the risk of anemia [15,16]. ITPA activity is modulated by ITPA gene single nucleotide polymorphisms (SNPs): reduced ITPA function has been fully documented from a missense variation in exon 2 (rs1127354), a splicing SNP located in the second intron (rs7270101) and a SNP in a noncoding region (rs6051702) [10,11,18]. ITPA activity is modulated by ITPA gene single nucleotide polymorphisms (SNPs): reduced ITPA function has been fully documented from a missense variation in exon 2 (rs1127354), a splicing SNP located in the second intron (rs7270101) and a SNP in a noncoding region (rs6051702) [10,11,18].…”

“…ITP is hydrolyzed by inosine triphosphatase (ITPA) enzyme and the deficiency of ITPA causes an increase in ITP levels; thus, there is a direct association with the greatest protection against the development of anemia [17]. The anemia-predicting role of these SNPs has been shown only at 4 weeks of therapy [10,11]. The anemia-predicting role of these SNPs has been shown only at 4 weeks of therapy [10,11].…”