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A truncating mutation in EPOR leads to hypo-responsiveness to erythropoietin with normal haemoglobin
The cytokine erythropoietin (EPO), signalling through the EPO receptor (EPO-R), is essential for the formation of red blood cells. We performed a genome-wide association study (GWAS) testing 32.5 million sequence variants for association with serum EPO levels in a set of 4187 individuals. We detect...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2018
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123817/ https://www.ncbi.nlm.nih.gov/pubmed/30271932 http://dx.doi.org/10.1038/s42003-018-0053-3 |
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| author | Oskarsson, Gudjon R. Kristjansson, Ragnar P. Lee, Amy L. Sveinbjornsson, Gardar Magnusson, Magnus K. Ivarsdottir, Erna V. Benonisdottir, Stefania Oddsson, Asmundur Davidsson, Olafur B. Saemundsdottir, Jona Halldorsson, Gisli H. Arthur, Joseph Arnadottir, Gudny A. Masson, Gisli Jensson, Brynjar O. Holm, Hilma Olafsson, Isleifur Onundarson, Pall T. Gudbjartsson, Daniel F. Norddahl, Gudmundur L. Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari |
| author_facet | Oskarsson, Gudjon R. Kristjansson, Ragnar P. Lee, Amy L. Sveinbjornsson, Gardar Magnusson, Magnus K. Ivarsdottir, Erna V. Benonisdottir, Stefania Oddsson, Asmundur Davidsson, Olafur B. Saemundsdottir, Jona Halldorsson, Gisli H. Arthur, Joseph Arnadottir, Gudny A. Masson, Gisli Jensson, Brynjar O. Holm, Hilma Olafsson, Isleifur Onundarson, Pall T. Gudbjartsson, Daniel F. Norddahl, Gudmundur L. Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari |
| author_sort | Oskarsson, Gudjon R. |
| collection | PubMed |
| description | The cytokine erythropoietin (EPO), signalling through the EPO receptor (EPO-R), is essential for the formation of red blood cells. We performed a genome-wide association study (GWAS) testing 32.5 million sequence variants for association with serum EPO levels in a set of 4187 individuals. We detect an association between a rare and well imputed stop-gained variant rs370865377[A] (p.Gln82Ter) in EPOR, carried by 1 in 550 Icelanders, and increased serum EPO levels (MAF = 0.09%, Effect = 1.47 SD, P = 3.3 × 10(−7)). We validated these findings by measuring serum EPO levels in 34 additional pairs of carriers and matched controls and found carriers to have 3.23-fold higher EPO levels than controls (P = 1.7 × 10(−6); P(combined) = 1.6 × 10(−11)). In contrast to previously reported EPOR mutations, p.Gln82Ter does not associate with haemoglobin levels (Effect = −0.045 SD, P = 0.32, N = 273,160), probably due to a compensatory EPO upregulation in response to EPO-R hypo-responsiveness. |
| format | Online Article Text |
| id | pubmed-6123817 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-61238172018-09-28 A truncating mutation in EPOR leads to hypo-responsiveness to erythropoietin with normal haemoglobin Oskarsson, Gudjon R. Kristjansson, Ragnar P. Lee, Amy L. Sveinbjornsson, Gardar Magnusson, Magnus K. Ivarsdottir, Erna V. Benonisdottir, Stefania Oddsson, Asmundur Davidsson, Olafur B. Saemundsdottir, Jona Halldorsson, Gisli H. Arthur, Joseph Arnadottir, Gudny A. Masson, Gisli Jensson, Brynjar O. Holm, Hilma Olafsson, Isleifur Onundarson, Pall T. Gudbjartsson, Daniel F. Norddahl, Gudmundur L. Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari Commun Biol Article The cytokine erythropoietin (EPO), signalling through the EPO receptor (EPO-R), is essential for the formation of red blood cells. We performed a genome-wide association study (GWAS) testing 32.5 million sequence variants for association with serum EPO levels in a set of 4187 individuals. We detect an association between a rare and well imputed stop-gained variant rs370865377[A] (p.Gln82Ter) in EPOR, carried by 1 in 550 Icelanders, and increased serum EPO levels (MAF = 0.09%, Effect = 1.47 SD, P = 3.3 × 10(−7)). We validated these findings by measuring serum EPO levels in 34 additional pairs of carriers and matched controls and found carriers to have 3.23-fold higher EPO levels than controls (P = 1.7 × 10(−6); P(combined) = 1.6 × 10(−11)). In contrast to previously reported EPOR mutations, p.Gln82Ter does not associate with haemoglobin levels (Effect = −0.045 SD, P = 0.32, N = 273,160), probably due to a compensatory EPO upregulation in response to EPO-R hypo-responsiveness. Nature Publishing Group UK 2018-05-17 /pmc/articles/PMC6123817/ /pubmed/30271932 http://dx.doi.org/10.1038/s42003-018-0053-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Oskarsson, Gudjon R. Kristjansson, Ragnar P. Lee, Amy L. Sveinbjornsson, Gardar Magnusson, Magnus K. Ivarsdottir, Erna V. Benonisdottir, Stefania Oddsson, Asmundur Davidsson, Olafur B. Saemundsdottir, Jona Halldorsson, Gisli H. Arthur, Joseph Arnadottir, Gudny A. Masson, Gisli Jensson, Brynjar O. Holm, Hilma Olafsson, Isleifur Onundarson, Pall T. Gudbjartsson, Daniel F. Norddahl, Gudmundur L. Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari A truncating mutation in EPOR leads to hypo-responsiveness to erythropoietin with normal haemoglobin |
| title | A truncating mutation in EPOR leads to hypo-responsiveness to erythropoietin with normal haemoglobin |
| title_full | A truncating mutation in EPOR leads to hypo-responsiveness to erythropoietin with normal haemoglobin |
| title_fullStr | A truncating mutation in EPOR leads to hypo-responsiveness to erythropoietin with normal haemoglobin |
| title_full_unstemmed | A truncating mutation in EPOR leads to hypo-responsiveness to erythropoietin with normal haemoglobin |
| title_short | A truncating mutation in EPOR leads to hypo-responsiveness to erythropoietin with normal haemoglobin |
| title_sort | truncating mutation in epor leads to hypo-responsiveness to erythropoietin with normal haemoglobin |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123817/ https://www.ncbi.nlm.nih.gov/pubmed/30271932 http://dx.doi.org/10.1038/s42003-018-0053-3 |
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