ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection.
BACKGROUND/OBJECTIVE:Genetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection. The aim of the present study was to investigate the associat...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4595504?pdf=render |
| _version_ | 1818267323295858688 |
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| author | Raoel Maan Adriaan J van der Meer Willem Pieter Brouwer Elisabeth P C Plompen Milan J Sonneveld Robert Roomer Annemiek A van der Eijk Zwier M A Groothuismink Bettina E Hansen Bart J Veldt Harry L A Janssen Andre Boonstra Robert J de Knegt |
| author_facet | Raoel Maan Adriaan J van der Meer Willem Pieter Brouwer Elisabeth P C Plompen Milan J Sonneveld Robert Roomer Annemiek A van der Eijk Zwier M A Groothuismink Bettina E Hansen Bart J Veldt Harry L A Janssen Andre Boonstra Robert J de Knegt |
| author_sort | Raoel Maan |
| collection | DOAJ |
| description | BACKGROUND/OBJECTIVE:Genetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection. The aim of the present study was to investigate the association between the functional ITPA variants and hematological side effects during antiviral therapy with pegylated interferon (PegIFN) and RBV. PATIENTS AND METHODS:This cohort study included all consecutive Caucasian patients treated for chronic HCV infection with PegIFN and RBV between 2000 and 2009 for whom a serum sample was available for genetic testing. The predicted inosine triphosphate pyrophosphatase (ITPase) activity was based on the genotypes of the SNPs rs1127354 and rs7270101. Decline in hemoglobin (Hb) during antiviral therapy, as well as dose reductions, blood transfusions and use of erythropoietin were assessed. RESULTS:In total, 213 patients were included. The predicted ITPase activity was normal among 152 (71%) patients; 61 (29%) patients had ITPase deficiency. By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p<0.001) and normal ITPase activity (Beta 0.89, 95%CI 0.64-1.14, p<0.001) were associated with more Hb decline at week 4 of treatment. Patients with normal ITPase activity underwent more dose adjustments of RBV than patients with ITPase deficiency (19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%) vs 0 (0%),p = 0.024). CONCLUSION:Genetic variants in the ITPA gene protected against RBV treatment-induced anemia among Caucasian patients with chronic HCV infection. Patients with normal ITPase activity underwent more dose reductions of RBV and received erythropoietin more frequently. |
| first_indexed | 2024-12-12T20:20:46Z |
| format | Article |
| id | doaj.art-90c09a9295144d4bbc02a649ba585bd1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T20:20:46Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-90c09a9295144d4bbc02a649ba585bd12022-12-22T00:13:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e013931710.1371/journal.pone.0139317ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection.Raoel MaanAdriaan J van der MeerWillem Pieter BrouwerElisabeth P C PlompenMilan J SonneveldRobert RoomerAnnemiek A van der EijkZwier M A GroothuisminkBettina E HansenBart J VeldtHarry L A JanssenAndre BoonstraRobert J de KnegtBACKGROUND/OBJECTIVE:Genetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection. The aim of the present study was to investigate the association between the functional ITPA variants and hematological side effects during antiviral therapy with pegylated interferon (PegIFN) and RBV. PATIENTS AND METHODS:This cohort study included all consecutive Caucasian patients treated for chronic HCV infection with PegIFN and RBV between 2000 and 2009 for whom a serum sample was available for genetic testing. The predicted inosine triphosphate pyrophosphatase (ITPase) activity was based on the genotypes of the SNPs rs1127354 and rs7270101. Decline in hemoglobin (Hb) during antiviral therapy, as well as dose reductions, blood transfusions and use of erythropoietin were assessed. RESULTS:In total, 213 patients were included. The predicted ITPase activity was normal among 152 (71%) patients; 61 (29%) patients had ITPase deficiency. By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p<0.001) and normal ITPase activity (Beta 0.89, 95%CI 0.64-1.14, p<0.001) were associated with more Hb decline at week 4 of treatment. Patients with normal ITPase activity underwent more dose adjustments of RBV than patients with ITPase deficiency (19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%) vs 0 (0%),p = 0.024). CONCLUSION:Genetic variants in the ITPA gene protected against RBV treatment-induced anemia among Caucasian patients with chronic HCV infection. Patients with normal ITPase activity underwent more dose reductions of RBV and received erythropoietin more frequently.http://europepmc.org/articles/PMC4595504?pdf=render |
| spellingShingle | Raoel Maan Adriaan J van der Meer Willem Pieter Brouwer Elisabeth P C Plompen Milan J Sonneveld Robert Roomer Annemiek A van der Eijk Zwier M A Groothuismink Bettina E Hansen Bart J Veldt Harry L A Janssen Andre Boonstra Robert J de Knegt ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection. PLoS ONE |
| title | ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection. |
| title_full | ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection. |
| title_fullStr | ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection. |
| title_full_unstemmed | ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection. |
| title_short | ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection. |
| title_sort | itpa polymorphisms are associated with hematological side effects during antiviral therapy for chronic hcv infection |
| url | http://europepmc.org/articles/PMC4595504?pdf=render |
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