The serotonin receptor 3E variant is a risk factor for female IBS-D
Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R ant...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/192381 |
| Acceso en línea: | https://hdl.handle.net/2445/192381 |
| Access Level: | acceso abierto |
| Palabra clave: | Malalties inflamatòries intestinals Malalties del tracte gastrointestinal Dones Inflammatory bowel diseases Gastrointestinal system diseases Women |
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The serotonin receptor 3E variant is a risk factor for female IBS-DFritz, NikolaBerens, SabrinaDong, YuanjunMartínez, CristinaSchmitteckert, StefanieHoughton, Lesley A.Goebel-Stengel, MiriamWahl, VerenaKabisch, MariaGötze, DorotheaD'Amato, MauroZheng, TenghaoRöth, RalpMönnikes, HubertTesarz, JonasEngel, FelicitasGauss, AnnikaRaithel, MartinAndresen, ViolaKeller, JuttaFrieling, ThomasPehl, ChristianStein-Thöringer, ChristophClarke, GerardKennedy, Paul J.Cryan, John F.Dinan, Timothy G.Quigley, Eamonn M. M.Spiller, RobinBeltrán, CarollMadrid, Ana MaríaTorres, VerónicaMayer, Emeran A.Sayuk, GregoryGazouli, MariaKaramanolis, GeorgeBustamante, MarionaEstivil, XavierRabionet Janssen, RaquelHoffmann, P.Malalties inflamatòries intestinalsMalalties del tracte gastrointestinalDonesInflammatory bowel diseasesGastrointestinal system diseasesWomenIrritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.Springer Verlag2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/192381Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1007/s00109-022-02244-wJournal of Molecular Medicine-JMM, 2022, vol. 100, num. 11, p. 1617-1627https://doi.org/10.1007/s00109-022-02244-wcc by (c) Fritz, Nikola et al., 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1923812026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
The serotonin receptor 3E variant is a risk factor for female IBS-D |
| title |
The serotonin receptor 3E variant is a risk factor for female IBS-D |
| spellingShingle |
The serotonin receptor 3E variant is a risk factor for female IBS-D Fritz, Nikola Malalties inflamatòries intestinals Malalties del tracte gastrointestinal Dones Inflammatory bowel diseases Gastrointestinal system diseases Women |
| title_short |
The serotonin receptor 3E variant is a risk factor for female IBS-D |
| title_full |
The serotonin receptor 3E variant is a risk factor for female IBS-D |
| title_fullStr |
The serotonin receptor 3E variant is a risk factor for female IBS-D |
| title_full_unstemmed |
The serotonin receptor 3E variant is a risk factor for female IBS-D |
| title_sort |
The serotonin receptor 3E variant is a risk factor for female IBS-D |
| dc.creator.none.fl_str_mv |
Fritz, Nikola Berens, Sabrina Dong, Yuanjun Martínez, Cristina Schmitteckert, Stefanie Houghton, Lesley A. Goebel-Stengel, Miriam Wahl, Verena Kabisch, Maria Götze, Dorothea D'Amato, Mauro Zheng, Tenghao Röth, Ralp Mönnikes, Hubert Tesarz, Jonas Engel, Felicitas Gauss, Annika Raithel, Martin Andresen, Viola Keller, Jutta Frieling, Thomas Pehl, Christian Stein-Thöringer, Christoph Clarke, Gerard Kennedy, Paul J. Cryan, John F. Dinan, Timothy G. Quigley, Eamonn M. M. Spiller, Robin Beltrán, Caroll Madrid, Ana María Torres, Verónica Mayer, Emeran A. Sayuk, Gregory Gazouli, Maria Karamanolis, George Bustamante, Mariona Estivil, Xavier Rabionet Janssen, Raquel Hoffmann, P. |
| author |
Fritz, Nikola |
| author_facet |
Fritz, Nikola Berens, Sabrina Dong, Yuanjun Martínez, Cristina Schmitteckert, Stefanie Houghton, Lesley A. Goebel-Stengel, Miriam Wahl, Verena Kabisch, Maria Götze, Dorothea D'Amato, Mauro Zheng, Tenghao Röth, Ralp Mönnikes, Hubert Tesarz, Jonas Engel, Felicitas Gauss, Annika Raithel, Martin Andresen, Viola Keller, Jutta Frieling, Thomas Pehl, Christian Stein-Thöringer, Christoph Clarke, Gerard Kennedy, Paul J. Cryan, John F. Dinan, Timothy G. Quigley, Eamonn M. M. Spiller, Robin Beltrán, Caroll Madrid, Ana María Torres, Verónica Mayer, Emeran A. Sayuk, Gregory Gazouli, Maria Karamanolis, George Bustamante, Mariona Estivil, Xavier Rabionet Janssen, Raquel Hoffmann, P. |
| author_role |
author |
| author2 |
Berens, Sabrina Dong, Yuanjun Martínez, Cristina Schmitteckert, Stefanie Houghton, Lesley A. Goebel-Stengel, Miriam Wahl, Verena Kabisch, Maria Götze, Dorothea D'Amato, Mauro Zheng, Tenghao Röth, Ralp Mönnikes, Hubert Tesarz, Jonas Engel, Felicitas Gauss, Annika Raithel, Martin Andresen, Viola Keller, Jutta Frieling, Thomas Pehl, Christian Stein-Thöringer, Christoph Clarke, Gerard Kennedy, Paul J. Cryan, John F. Dinan, Timothy G. Quigley, Eamonn M. M. Spiller, Robin Beltrán, Caroll Madrid, Ana María Torres, Verónica Mayer, Emeran A. Sayuk, Gregory Gazouli, Maria Karamanolis, George Bustamante, Mariona Estivil, Xavier Rabionet Janssen, Raquel Hoffmann, P. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Malalties inflamatòries intestinals Malalties del tracte gastrointestinal Dones Inflammatory bowel diseases Gastrointestinal system diseases Women |
| topic |
Malalties inflamatòries intestinals Malalties del tracte gastrointestinal Dones Inflammatory bowel diseases Gastrointestinal system diseases Women |
| description |
Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://hdl.handle.net/2445/192381 |
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https://hdl.handle.net/2445/192381 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1007/s00109-022-02244-w Journal of Molecular Medicine-JMM, 2022, vol. 100, num. 11, p. 1617-1627 https://doi.org/10.1007/s00109-022-02244-w |
| dc.rights.none.fl_str_mv |
cc by (c) Fritz, Nikola et al., 2022 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess |
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cc by (c) Fritz, Nikola et al., 2022 http://creativecommons.org/licenses/by/3.0/es/ |
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openAccess |
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application/pdf |
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Springer Verlag |
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Springer Verlag |
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Articles publicats en revistes (Genètica, Microbiologia i Estadística) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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15,300719 |