Document Detail


Pre-treatment role of inosine triphosphate pyrophosphatase polymorphism for predicting anemia in Egyptian hepatitis C virus patients.
MedLine Citation:
PMID:  23538996     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA) polymorphism in Egyptian chronic hepatitis C virus (HCV) patients.
METHODS: The human genomic DNA of all patients was extracted from peripheral blood cells in order to determine the single nucleotide polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102 treatment-naive Egyptian patients with chronic HCV. All patients had no evidence of cardiovascular or renal diseases. They received a combination treatment of pegylated interferon α (PEG-IFNα) as a weekly subcutaneous dose plus an oral weight-adjusted dose of ribavirin (RBV). The majority received PEG-IFNα2a (70.6%) while 29.4% received PEG-IFNα2b. The planned duration of treatment was 24-48 wk according to the viral kinetics throughout the course of treatment. Pre-treatment liver biopsy was done for each patient for evaluation of fibrosis stage and liver disease activity. The basal viral load level was detected quantitatively by real time PCR while viral load throughout the treatment course was performed qualitatively by COBAS TaqMan assay.
RESULTS: Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC patients than for non-CC patients, particularly at weeks 4 and 8 (P = 0.047 and 0.034, respectively). During the first 12 wk of treatment, CC patients had significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at weeks 8 and 12, respectively, (P = 0.024 and 0.038). Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P = 0.021). The percentage of CC patients with RBV dose reduction was significantly greater than that of non-CC patients (77.4% vs 44.4%, P = 0.044). Multivariate analysis identified only the percentage of RBV dose as a predictor for Hb decline. Platelet decline was significantly higher in non-CC patients than CC patients at weeks 12, 24 and 48 (P = 0.018, 0.009 and 0.026, respectively).
CONCLUSION: Rs1127354 ITPA polymorphism plays a decisive role in protecting against treatment-induced anemia and the need for RBV dose reduction in Egyptian HCV patients.
Authors:
Walaa H Ahmed; Norihiro Furusyo; Saad Zaky; Abeer Sharaf Eldin; Hany Aboalam; Eiichi Ogawa; Masayuki Murata; Jun Hayashi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  19     ISSN:  2219-2840     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-29     Completed Date:  2013-12-06     Revised Date:  2014-05-20    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  1387-95     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Anemia / blood,  chemically induced,  enzymology,  genetics,  prevention & control*
Antiviral Agents / adverse effects*
Biological Markers / blood
Drug Therapy, Combination
Egypt / epidemiology
Female
Gene Frequency
Genetic Predisposition to Disease
Hemoglobins / metabolism
Hepatitis C, Chronic / diagnosis,  drug therapy*,  enzymology,  epidemiology,  genetics
Humans
Interferon-alpha / adverse effects*
Logistic Models
Male
Multivariate Analysis
Odds Ratio
Phenotype
Polyethylene Glycols / adverse effects*
Polymorphism, Single Nucleotide*
Pyrophosphatases / genetics*
Recombinant Proteins / adverse effects
Ribavirin / adverse effects*
Risk Factors
Time Factors
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antiviral Agents; 0/Biological Markers; 0/Hemoglobins; 0/Interferon-alpha; 0/Polyethylene Glycols; 0/Recombinant Proteins; 0/peginterferon alfa-2a; 0/peginterferon alfa-2b; 49717AWG6K/Ribavirin; EC 3.6.1.-/Pyrophosphatases; EC 3.6.1.19/ITPA protein, human
Comments/Corrections

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