Variants in the ITPA Gene Protect Against Ribavirin-Induced Hemolytic Anemia in HIV/HCV-Coinfected Patients With All HCV Genotypes

Abstract

This study confirms that polymorphisms in the ITPA gene are associated with protection from RBV-induced anemia in HIV/HCV-coinfected patients but not improved clinical outcomes.

Association of ITPA Gene Polymorphisms and the Risk of Ribavirin-Induced Anemia in HIV/Hepatitis C Virus (HCV)-Coinfected Patients Receiving HCV Combination Therapy

“…Recent evidence indicates that ITP protects against RBV-induced anemia by substituting for GTP (depleted by RBV) in the biosynthesis of ATP (13). Since ITP intracellular levels are dependent on ITPA activity, which in turn is modulated by functional polymorphisms in the ITPA gene (26), these polymorphisms may in the end determine the degree of protection against RBV-induced hemolytic anemia in HIV/HCVcoinfected patients, as has been recently reported (19,23) and our work suggests.…”

“…Data regarding the association of ITPA polymorphism and combination HCV treatment outcome are quite controversial, with some studies showing such an association (14), whereas others (7,19,23,31,32) do not see any association between the ITPA gene, anemia, and SVR. This association may only be the reflection of decreased treatment efficacy due to dose reduction of RBV in patients with severe anemia, because the potential of RBV dose reduction to limit treatment efficacy is well-known (28).…”

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

“…The polymorphism rs7072101, which is functional and often it is studied in association with the rs1127354 (Caviglia et al, 2012;D'Avolio et al, 2012a;Fellay et al, 2010;Naggie et al, 2012;Rau et al, 2012;Thompson et al, 2010a;Thompson et al, 2010c) seems to have minor clinical significance, compared to the other.…”

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

“…This was in agreement with Delvaux et al [23] who reported that in Brazilian population the frequency of allelic dis tribution at rs7270101 and rs1127354 shows high rates of the genotypes AA (84%) and CC (94.3%), respectively. Also, Domingo et al [24], D'Avolio et al [25], Naggie et al [26] Rau et al [27] who demonstrated that the majority of European indi viduals carry AA and CC genotypes for rs7270101 and rs1127354, respectively. Also, Ochi et al [28], Tanaka et al [29], Kim et al [18] reported that among Japanese and Korean populations, the CC genotype is also more prevalent at rs1127354, but they are monoal lelic for the rs7270101 AA genotype.…”