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IL28B and IL10R −1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort

BACKGROUND: Previous studies have shown that single nucleotide polymorphisms (SNP) in IL28B and IL10R are associated with sustained virological response (SVR) in chronic hepatitis C patients treated with pegilated interferon plus ribavirin (P/R). The present study extends our earlier investigations...

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Autores principales: Pár, Alajos, Pár, Gabriella, Tornai, István, Szalay, Ferenc, Várszegi, Dalma, Fráter, Edit, Papp, Mária, Lengyel, Gabriella, Fehér, János, Varga, Márta, Gervain, Judit, Schuller, János, Nemes, Zsuzsanna, Péterfi, Zoltán, Tusnádi, Anna, Hunyady, Béla, Haragh, Attila, Szinku, Zsolt, Vincze, Áron, Szereday, László, Kisfali, Péter, Melegh, Béla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896726/
https://www.ncbi.nlm.nih.gov/pubmed/24398031
http://dx.doi.org/10.1186/1756-0500-7-12
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author Pár, Alajos
Pár, Gabriella
Tornai, István
Szalay, Ferenc
Várszegi, Dalma
Fráter, Edit
Papp, Mária
Lengyel, Gabriella
Fehér, János
Varga, Márta
Gervain, Judit
Schuller, János
Nemes, Zsuzsanna
Péterfi, Zoltán
Tusnádi, Anna
Hunyady, Béla
Haragh, Attila
Szinku, Zsolt
Vincze, Áron
Szereday, László
Kisfali, Péter
Melegh, Béla
author_facet Pár, Alajos
Pár, Gabriella
Tornai, István
Szalay, Ferenc
Várszegi, Dalma
Fráter, Edit
Papp, Mária
Lengyel, Gabriella
Fehér, János
Varga, Márta
Gervain, Judit
Schuller, János
Nemes, Zsuzsanna
Péterfi, Zoltán
Tusnádi, Anna
Hunyady, Béla
Haragh, Attila
Szinku, Zsolt
Vincze, Áron
Szereday, László
Kisfali, Péter
Melegh, Béla
author_sort Pár, Alajos
collection PubMed
description BACKGROUND: Previous studies have shown that single nucleotide polymorphisms (SNP) in IL28B and IL10R are associated with sustained virological response (SVR) in chronic hepatitis C patients treated with pegilated interferon plus ribavirin (P/R). The present study extends our earlier investigations on a large East-Central European cohort. The allele frequencies of IL28B and IL10R in genotype 1 HCV infection were compared with that of healthy controls for the purpose of examining the relationship between the polymorphisms and the SVR to P/R treatment. METHODS: A total of 748 chronic HCV1 infected patients (365 male, 383 female; 18–82 years) and 105 voluntary blood donors as controls were enrolled. Four hundred and twenty HCV patients were treated with P/R for 24–72 weeks, out of them 195 (46.4%) achieved SVR. The IL28 rs12979860 SNP was determined using Custom Taqman SNP Genotyping Assays. The IL10R −1087 (also known as IL10R −1082 (rs1800896) promoter region SNP was determined by RT-PCR and restriction fragment length polymorphism analysis. RESULTS: The IL28B CC genotype occurred with lower frequency in HCV patients than in controls (26.1% vs 51.4%, p<0.001). P/R treated patients with the IL28B CC genotype achieved higher SVR rate, as compared to patients with CT (58.6% vs 40.8%, p=0.002). The prevalence of IL10R −1087 GG genotype was lower in patients than in controls (31.8 % vs 52.2%, p<0.001). Among patients achieving SVR, the IL10R −1087 GG genotype occurred with higher frequency than the AA (32.0% vs 17.4%, p=0.013). The IL28B T allele plus IL10R A allele combination was found with higher prevalence in patients than in controls (52% vs 20.7%, p<0.001). The IL28B CC plus IL10R A allele combination occurred with higher frequency among patients with SVR than in non-responders (21.3% vs 12.8%, p=0.026). Both the IL28B CC plus IL10R GG and the IL28B CC plus IL10R A allele combinations occurred with lower frequency in patients than in controls. CONCLUSIONS: In our HCV1 patients, both the IL28B CC and IL10R GG genotypes are associated with clearance of HCV. Moreover, distinct IL28B and IL10R allele combinations appear to be protective against chronic HCV1 infection and predictors of response to P/R therapy.
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spelling pubmed-38967262014-01-22 IL28B and IL10R −1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort Pár, Alajos Pár, Gabriella Tornai, István Szalay, Ferenc Várszegi, Dalma Fráter, Edit Papp, Mária Lengyel, Gabriella Fehér, János Varga, Márta Gervain, Judit Schuller, János Nemes, Zsuzsanna Péterfi, Zoltán Tusnádi, Anna Hunyady, Béla Haragh, Attila Szinku, Zsolt Vincze, Áron Szereday, László Kisfali, Péter Melegh, Béla BMC Res Notes Research Article BACKGROUND: Previous studies have shown that single nucleotide polymorphisms (SNP) in IL28B and IL10R are associated with sustained virological response (SVR) in chronic hepatitis C patients treated with pegilated interferon plus ribavirin (P/R). The present study extends our earlier investigations on a large East-Central European cohort. The allele frequencies of IL28B and IL10R in genotype 1 HCV infection were compared with that of healthy controls for the purpose of examining the relationship between the polymorphisms and the SVR to P/R treatment. METHODS: A total of 748 chronic HCV1 infected patients (365 male, 383 female; 18–82 years) and 105 voluntary blood donors as controls were enrolled. Four hundred and twenty HCV patients were treated with P/R for 24–72 weeks, out of them 195 (46.4%) achieved SVR. The IL28 rs12979860 SNP was determined using Custom Taqman SNP Genotyping Assays. The IL10R −1087 (also known as IL10R −1082 (rs1800896) promoter region SNP was determined by RT-PCR and restriction fragment length polymorphism analysis. RESULTS: The IL28B CC genotype occurred with lower frequency in HCV patients than in controls (26.1% vs 51.4%, p<0.001). P/R treated patients with the IL28B CC genotype achieved higher SVR rate, as compared to patients with CT (58.6% vs 40.8%, p=0.002). The prevalence of IL10R −1087 GG genotype was lower in patients than in controls (31.8 % vs 52.2%, p<0.001). Among patients achieving SVR, the IL10R −1087 GG genotype occurred with higher frequency than the AA (32.0% vs 17.4%, p=0.013). The IL28B T allele plus IL10R A allele combination was found with higher prevalence in patients than in controls (52% vs 20.7%, p<0.001). The IL28B CC plus IL10R A allele combination occurred with higher frequency among patients with SVR than in non-responders (21.3% vs 12.8%, p=0.026). Both the IL28B CC plus IL10R GG and the IL28B CC plus IL10R A allele combinations occurred with lower frequency in patients than in controls. CONCLUSIONS: In our HCV1 patients, both the IL28B CC and IL10R GG genotypes are associated with clearance of HCV. Moreover, distinct IL28B and IL10R allele combinations appear to be protective against chronic HCV1 infection and predictors of response to P/R therapy. BioMed Central 2014-01-08 /pmc/articles/PMC3896726/ /pubmed/24398031 http://dx.doi.org/10.1186/1756-0500-7-12 Text en Copyright © 2014 Pár et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Pár, Alajos
Pár, Gabriella
Tornai, István
Szalay, Ferenc
Várszegi, Dalma
Fráter, Edit
Papp, Mária
Lengyel, Gabriella
Fehér, János
Varga, Márta
Gervain, Judit
Schuller, János
Nemes, Zsuzsanna
Péterfi, Zoltán
Tusnádi, Anna
Hunyady, Béla
Haragh, Attila
Szinku, Zsolt
Vincze, Áron
Szereday, László
Kisfali, Péter
Melegh, Béla
IL28B and IL10R −1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort
title IL28B and IL10R −1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort
title_full IL28B and IL10R −1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort
title_fullStr IL28B and IL10R −1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort
title_full_unstemmed IL28B and IL10R −1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort
title_short IL28B and IL10R −1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort
title_sort il28b and il10r −1087 polymorphisms are protective for chronic genotype 1 hcv infection and predictors of response to interferon-based therapy in an east-central european cohort
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896726/
https://www.ncbi.nlm.nih.gov/pubmed/24398031
http://dx.doi.org/10.1186/1756-0500-7-12
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