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-HT(3) receptor family. 5-HT(3)Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT(3...

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Autores principales: 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, Ralph, 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, Raquel, Hoffmann, Per, Nöthen, Markus M., Heilmann-Heimbach, Stefanie, Schmidt, Börge, Franke, André, Lieb, Wolfgang, Herzog, Wolfgang, Boeckxstaens, Guy, Wouters, Mira M., Simrén, Magnus, Rappold, Gudrun A., Vicario, Maria, Santos, Javier, Schaefert, Rainer, Lorenzo-Bermejo, Justo, Niesler, Beate
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9592668/
https://www.ncbi.nlm.nih.gov/pubmed/36121467
http://dx.doi.org/10.1007/s00109-022-02244-w
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author 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, Ralph
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, Raquel
Hoffmann, Per
Nöthen, Markus M.
Heilmann-Heimbach, Stefanie
Schmidt, Börge
Franke, André
Lieb, Wolfgang
Herzog, Wolfgang
Boeckxstaens, Guy
Wouters, Mira M.
Simrén, Magnus
Rappold, Gudrun A.
Vicario, Maria
Santos, Javier
Schaefert, Rainer
Lorenzo-Bermejo, Justo
Niesler, Beate
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, Ralph
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, Raquel
Hoffmann, Per
Nöthen, Markus M.
Heilmann-Heimbach, Stefanie
Schmidt, Börge
Franke, André
Lieb, Wolfgang
Herzog, Wolfgang
Boeckxstaens, Guy
Wouters, Mira M.
Simrén, Magnus
Rappold, Gudrun A.
Vicario, Maria
Santos, Javier
Schaefert, Rainer
Lorenzo-Bermejo, Justo
Niesler, Beate
author_sort Fritz, Nikola
collection PubMed
description Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT(3) receptor family. 5-HT(3)Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT(3)R 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00109-022-02244-w.
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spelling pubmed-95926682022-10-26 The serotonin receptor 3E variant is a risk factor for female IBS-D 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, Ralph 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, Raquel Hoffmann, Per Nöthen, Markus M. Heilmann-Heimbach, Stefanie Schmidt, Börge Franke, André Lieb, Wolfgang Herzog, Wolfgang Boeckxstaens, Guy Wouters, Mira M. Simrén, Magnus Rappold, Gudrun A. Vicario, Maria Santos, Javier Schaefert, Rainer Lorenzo-Bermejo, Justo Niesler, Beate J Mol Med (Berl) Original Article Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT(3) receptor family. 5-HT(3)Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT(3)R 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00109-022-02244-w. Springer Berlin Heidelberg 2022-09-19 2022 /pmc/articles/PMC9592668/ /pubmed/36121467 http://dx.doi.org/10.1007/s00109-022-02244-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
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, Ralph
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, Raquel
Hoffmann, Per
Nöthen, Markus M.
Heilmann-Heimbach, Stefanie
Schmidt, Börge
Franke, André
Lieb, Wolfgang
Herzog, Wolfgang
Boeckxstaens, Guy
Wouters, Mira M.
Simrén, Magnus
Rappold, Gudrun A.
Vicario, Maria
Santos, Javier
Schaefert, Rainer
Lorenzo-Bermejo, Justo
Niesler, Beate
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
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_short The serotonin receptor 3E variant is a risk factor for female IBS-D
title_sort serotonin receptor 3e variant is a risk factor for female ibs-d
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9592668/
https://www.ncbi.nlm.nih.gov/pubmed/36121467
http://dx.doi.org/10.1007/s00109-022-02244-w
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