ITPA gene polymorphisms significantly affect hemoglobin decline and treatment outcomes in patients coinfected with HIV and HCV
| Autor: | Martin Trippler, Dawn A. Fishbein, Michael A. Polis, Seerat Poonia, Joerg F. Schlaak, Shyam Kottilil, Zonghui Hu, Anu Osinusi, Susanna Naggie, Emily K. Funk, Henry Masur |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Hemolytic anemia Genotype Anemia Medizin HIV Infections Pilot Projects Single-nucleotide polymorphism Biology Antiviral Agents Polymorphism Single Nucleotide Article Hemoglobins chemistry.chemical_compound Pegylated interferon Virology Ribavirin medicine Humans Prospective Studies Pyrophosphatases Rapid Virologic Response Coinfection Hepatitis C Chronic Middle Aged medicine.disease Treatment Outcome Infectious Diseases chemistry Female Interferons Hemoglobin ITPA medicine.drug |
| Zdroj: | Journal of Medical Virology. 84:1106-1114 |
| ISSN: | 0146-6615 |
| DOI: | 10.1002/jmv.23302 |
| Popis: | Published studies have described a strong association with a single-nucleotide polymorphism (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene and ribavirin (RBV)-induced hemolytic anemia in HCV-infected patients receiving pegylated interferon (pegIFN) and RBV. This study sought to evaluate the effect of these polymorphisms on anemia, hemoglobin reduction, HCV kinetics, and treatment outcomes. Sixty-three patients coinfected with HIV and HCV and 58 patients infected with HCV only were treated with pegIFN/RBV were genotyped using the ABI Taq-Man allelic discrimination kit for the 2 ITPA SNP variants rs1127354 and rs7270101. A composite variable of ITPA deficiency using both SNPs was created as previously reported. Statistical analysis was performed using Mann-Whitney test or Chi square/Fishers exact test for categorical data and mixed model analysis for multiple variables. Thirty-five patients (30%) were predicted to have reduced ITPA activity. ITPA deficiency was found to be protective against the development of hemoglobin reduction >3 g/dl over the course of treatment. The rates of hemoglobin reduction >3 g/dl decreased in correlation with the severity of ITPA deficiency. ITPA deficiency was associated with slower hemoglobin decline early in treatment (week 4, P = 0.020) and rapid virologic response (RVR) at week 4 (P = 0.017) in patients coinfected with HIV and HCV. ITPA polymorphisms are associated with hemoglobin decline and in patients coinfected with HIV and HCV it is also associated with early virologic outcomes. Determination of ITPA polymorphisms may allow prediction of RBV-induced anemia and earlier initiation of supportive care to ensure optimal therapeutic outcomes. |
| Databáze: | OpenAIRE |
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