Association of ITPA polymorphisms rs6051702/rs1127354 instead of rs7270101/rs1127354 as predictor of ribavirin-associated anemia in chronic hepatitis C treated patients.
Functional variants rs7270101 and rs1127354 of inosine triphosphatase (ITPA) were recently found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no definitive data are yet available on the role of no functional rs6051702 polymorphism. Since a simultaneous evaluation of the three ITPA SNPs for hemolytic anemia has not yet been investigated, we aimed to understand the contribution of each SNPs and its potential clinical use to predict anemia in HCV treated patients. A retrospective analysis included 379 HCV treated patients. The ITPA variants rs6051702, rs7270101 and rs1127354 were genotyped and tested for association with achieving anemia at week 4. We also investigated, using multivariate logistic regression, the impact of each single and paired associated polymorphism on anemia onset. All SNPs were associated with Hb decrease. The carrier of at least one variant allele in the functional ITPA SNPs was associated with a lower decrement of Hb, as compared to patients without a variant allele. In multivariate logistic regression analyses the carrier of a variant allele in the rs6051702/rs1127354 association (OR=0.11, p=1.75×10(-5)) and Hb at baseline (OR=1.51, p=1.21×10(-4)) were independently associated with protection against clinically significant anemia at week 4. All ITPA polymorphisms considered were shown to be significantly associated with anemia onset. A multivariate regression model based on ITPA genetic polymorphisms was developed for predicting the risk of anemia. Considering the characterization of pre-therapy anemia predictors, rs6051702 SNP in association to rs1127354 is more informative in order to avoid this relevant adverse event.
Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy. Electronic address: antonio.davolio@unito.it.
Antonio
A
D'Avolio
Amedeo
A
De Nicolò
Jessica
J
Cusato
Alessia
A
Ciancio
Lucio
L
Boglione
Silvia
S
Strona
Giuseppe
G
Cariti
Giulia
G
Troshina
Gian Paolo
GP
Caviglia
Antonina
A
Smedile
Mario
M
Rizzetto
Giovanni
G
Di Perri
D000328:Adult; D000740:Anemia / Q000209:etiology / Q000235:genetics*; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D012189:Retrospective Studies; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D000097630:Inosine Triphosphatase
D000998:Antiviral Agents; D011755:Pyrophosphatases; D012254:Ribavirin; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase
Adverse event; Anemia; HCV; Hb; IQR; ITP; ITPA; PEG/IFN; RBV; Ribavirin; SNPs; SVR; Single nucleotide polymorphism; TDM; WT; haemoglobin; hepatitis C virus; inosine triphosphatase; inosine triphosphate; inter-quartile range; pegylated interferon; ribavirin; single nucleotide polymorphisms; sustained virological response; therapeutic drug monitoring; wild type