Tryptophan Breakdown in Patients with HCV Infection is Influenced by IL28B Polymorphism
Until recently, the standard treatment of chronic hepatitis C virus (HCV) infection was a combination therapy with PEG-IFN-α plus ribavirin. Previous studies have proven that several markers predict the outcome of such therapy, e.g., pretreatment plasma levels of interferon inducible protein IP-10,...
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MDPI AG
2015-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | http://www.mdpi.com/1424-8247/8/2/337 |
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| author | Heinz Zoller Annina Jenal Albert F. Staettermayer Sebastian Schroecksnadel Peter Ferenci Dietmar Fuchs |
| author_facet | Heinz Zoller Annina Jenal Albert F. Staettermayer Sebastian Schroecksnadel Peter Ferenci Dietmar Fuchs |
| author_sort | Heinz Zoller |
| collection | DOAJ |
| description | Until recently, the standard treatment of chronic hepatitis C virus (HCV) infection was a combination therapy with PEG-IFN-α plus ribavirin. Previous studies have proven that several markers predict the outcome of such therapy, e.g., pretreatment plasma levels of interferon inducible protein IP-10, HCV RNA and IL28B-related single nucleotide polymorphisms (SNP). Altered activity of tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been also shown in patients suffering from HCV infection. In this study, we investigated whether IL28B SNP in patients infected with HCV is related to the tryptophan breakdown rate. Before therapy, serum tryptophan and kynurenine concentrations were determined in 25 patients with established HCV infection and the kynurenine to tryptophan ratio (KYN/TRP) was calculated as an estimate of the tryptophan breakdown rate. In parallel, neopterin and nitrite concentrations were determined. A significant difference of serum KYN/TRP existed between the three IL28B polymorphism groups: C/C genotype had the highest and T/T genotype had the lowest KYN/TRP (p < 0.05). Likewise, C/C genotype was associated with higher KYN/TRP than non-C/C genotype (p = 0.01). There was a smaller difference between the three groups regarding the absolute kynurenine concentrations, the C/C genotype being associated with higher kynurenine concentrations. None of the other comparisons revealed any statistical significance. In conclusion, patients with C/C genotype presented with the highest tryptophan breakdown rate already before antiretroviral therapy with IFN-α/ribavirin. The differences in tryptophan metabolism might relate to HCV clearance and also to side effects of IFN-α therapy. |
| first_indexed | 2024-12-10T14:17:16Z |
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| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-12-10T14:17:16Z |
| publishDate | 2015-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-e3464dfb407144feaf6c1a230e097e682022-12-22T01:45:19ZengMDPI AGPharmaceuticals1424-82472015-06-018233735010.3390/ph8020337ph8020337Tryptophan Breakdown in Patients with HCV Infection is Influenced by IL28B PolymorphismHeinz Zoller0Annina Jenal1Albert F. Staettermayer2Sebastian Schroecksnadel3Peter Ferenci4Dietmar Fuchs5Department of Internal Medicine, Biocenter, Innsbruck Medical University, Innsbruck 6020, AustriaDivision of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck 6020, AustriaDepartment of Medicine III, Medical University of Vienna, Vienna 1090, AustriaDivision of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck 6020, AustriaDepartment of Medicine III, Medical University of Vienna, Vienna 1090, AustriaDivision of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck 6020, AustriaUntil recently, the standard treatment of chronic hepatitis C virus (HCV) infection was a combination therapy with PEG-IFN-α plus ribavirin. Previous studies have proven that several markers predict the outcome of such therapy, e.g., pretreatment plasma levels of interferon inducible protein IP-10, HCV RNA and IL28B-related single nucleotide polymorphisms (SNP). Altered activity of tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been also shown in patients suffering from HCV infection. In this study, we investigated whether IL28B SNP in patients infected with HCV is related to the tryptophan breakdown rate. Before therapy, serum tryptophan and kynurenine concentrations were determined in 25 patients with established HCV infection and the kynurenine to tryptophan ratio (KYN/TRP) was calculated as an estimate of the tryptophan breakdown rate. In parallel, neopterin and nitrite concentrations were determined. A significant difference of serum KYN/TRP existed between the three IL28B polymorphism groups: C/C genotype had the highest and T/T genotype had the lowest KYN/TRP (p < 0.05). Likewise, C/C genotype was associated with higher KYN/TRP than non-C/C genotype (p = 0.01). There was a smaller difference between the three groups regarding the absolute kynurenine concentrations, the C/C genotype being associated with higher kynurenine concentrations. None of the other comparisons revealed any statistical significance. In conclusion, patients with C/C genotype presented with the highest tryptophan breakdown rate already before antiretroviral therapy with IFN-α/ribavirin. The differences in tryptophan metabolism might relate to HCV clearance and also to side effects of IFN-α therapy.http://www.mdpi.com/1424-8247/8/2/337IL28B polymorphismtryptophan breakdownindoleamine 2,3-dioxygenasekynurenine to tryptophan rationeopterin |
| spellingShingle | Heinz Zoller Annina Jenal Albert F. Staettermayer Sebastian Schroecksnadel Peter Ferenci Dietmar Fuchs Tryptophan Breakdown in Patients with HCV Infection is Influenced by IL28B Polymorphism Pharmaceuticals IL28B polymorphism tryptophan breakdown indoleamine 2,3-dioxygenase kynurenine to tryptophan ratio neopterin |
| title | Tryptophan Breakdown in Patients with HCV Infection is Influenced by IL28B Polymorphism |
| title_full | Tryptophan Breakdown in Patients with HCV Infection is Influenced by IL28B Polymorphism |
| title_fullStr | Tryptophan Breakdown in Patients with HCV Infection is Influenced by IL28B Polymorphism |
| title_full_unstemmed | Tryptophan Breakdown in Patients with HCV Infection is Influenced by IL28B Polymorphism |
| title_short | Tryptophan Breakdown in Patients with HCV Infection is Influenced by IL28B Polymorphism |
| title_sort | tryptophan breakdown in patients with hcv infection is influenced by il28b polymorphism |
| topic | IL28B polymorphism tryptophan breakdown indoleamine 2,3-dioxygenase kynurenine to tryptophan ratio neopterin |
| url | http://www.mdpi.com/1424-8247/8/2/337 |
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