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Title: | The serotonin receptor 3E variant is a risk factor for female IBS-D |
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, 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. |
Keywords: | Malalties inflamatòries intestinals Malalties del tracte gastrointestinal Dones Inflammatory bowel diseases Gastrointestinal system diseases Women |
Issue Date: | Nov-2022 |
Publisher: | Springer Verlag |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1007/s00109-022-02244-w |
It is part of: | Journal of Molecular Medicine-JMM, 2022, vol. 100, num. 11, p. 1617-1627 |
URI: | https://hdl.handle.net/2445/192381 |
Related resource: | https://doi.org/10.1007/s00109-022-02244-w |
ISSN: | 0946-2716 |
Appears in Collections: | Articles publicats en revistes (Genètica, Microbiologia i Estadística) |
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