Linked Life Data

21274861

Source:http://linkedlifedata.com/resource/pubmed/id/21274861

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-28
pubmed:abstractText
Two functional variants in the inosine triphosphatase (ITPA) gene causing inosine triphosphatase (ITPase) deficiency protect against ribavirin (RBV)-induced hemolytic anemia and the need for RBV dose reduction in patients with genotype 1 hepatitis C virus (HCV). No data are available for genotype 2/3 HCV. We evaluated the association between the casual ITPA variants and on-treatment anemia in a well-characterized cohort of genotype 2/3 patients treated with variable-duration pegylated interferon alfa-2b (PEG-IFN-?2b) and RBV. Two hundred thirty-eight Caucasian patients were included in this retrospective study [185 (78%) with genotype 2 and 53 (22%) with genotype 3]. Patients were treated with PEG-IFN-?2b plus weight-based RBV (1000/1200 mg) for 12 (n = 109) or 24 weeks (n = 129). The ITPA polymorphisms rs1127354 and rs7270101 were genotyped, and an ITPase deficiency variable was defined that combined both ITPA variants according to their effect on ITPase activity. The primary endpoint was hemoglobin (Hb) reduction in week 4. We also considered Hb reduction over the course of therapy, the need for RBV dose modification, and the rate of sustained virological response (SVR). The ITPA variants were strongly and independently associated with protection from week 4 anemia (P = 10(-6) for rs1127354 and P = 10(-7) for rs7270101). Combining the variants into the ITPase deficiency variable increased the strength of association (P = 10(-11) ). ITPase deficiency protected against anemia throughout treatment. ITPase deficiency was associated with a delayed time to an Hb level < 10 g/dL (hazard ratio = 0.25, 95% confidence interval = 0.08-0.84, P = 0.025) but not with the rate of RBV dose modification (required per protocol at Hb < 9.5 g/dL). There was no association between the ITPA variants and SVR. Conclusion: Two ITPA variants were strongly associated with protection against treatment-related anemia in patients with genotype 2/3 HCV, but they did not decrease the need for RBV dose reduction or increase the rate of SVR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1527-3350
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 American Association for the Study of Liver Diseases.
pubmed:issnType
Electronic
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
389-95
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21274861-Adult, pubmed-meshheading:21274861-Anemia, pubmed-meshheading:21274861-Antiviral Agents, pubmed-meshheading:21274861-Dose-Response Relationship, Drug, pubmed-meshheading:21274861-Drug Therapy, Combination, pubmed-meshheading:21274861-Female, pubmed-meshheading:21274861-Genotype, pubmed-meshheading:21274861-Hepacivirus, pubmed-meshheading:21274861-Hepatitis C, pubmed-meshheading:21274861-Humans, pubmed-meshheading:21274861-Interferon-alpha, pubmed-meshheading:21274861-Italy, pubmed-meshheading:21274861-Linear Models, pubmed-meshheading:21274861-Male, pubmed-meshheading:21274861-Middle Aged, pubmed-meshheading:21274861-Polyethylene Glycols, pubmed-meshheading:21274861-Polymorphism, Genetic, pubmed-meshheading:21274861-Pyrophosphatases, pubmed-meshheading:21274861-Recombinant Proteins, pubmed-meshheading:21274861-Retrospective Studies, pubmed-meshheading:21274861-Ribavirin, pubmed-meshheading:21274861-Risk Factors, pubmed-meshheading:21274861-Treatment Outcome
pubmed:year
2011
pubmed:articleTitle
Inosine triphosphatase genetic variants are protective against anemia during antiviral therapy for HCV2/3 but do not decrease dose reductions of RBV or increase SVR.
pubmed:affiliation
Duke Clinical Research Institute, Durham, NC, USA.
pubmed:publicationType
Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Multicenter Study