The serotonin receptor 3E variant is a risk factor for female IBS-D

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• dc.contributor.author Fritz, Nikola
• dc.contributor.author Bustamante Pineda, Mariona
• dc.contributor.author Niesler, Beate
• dc.date.accessioned 2022-11-02T07:29:03Z
• dc.date.available 2022-11-02T07:29:03Z
• dc.date.issued 2022
• dc.description.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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Fritz N, Berens S, Dong Y, Martínez C, Schmitteckert S, Houghton LA et al. The serotonin receptor 3E variant is a risk factor for female IBS-D. J Mol Med (Berl). 2022 Nov;100(11):1617-27. DOI: 10.1007/s00109-022-02244-w
• dc.identifier.doi http://dx.doi.org/10.1007/s00109-022-02244-w
• dc.identifier.issn 0946-2716
• dc.identifier.uri http://hdl.handle.net/10230/54650
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof J Mol Med (Berl). 2022 Nov;100(11):1617-27
• dc.rights © The Author(s) 2022. 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 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/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Females
• dc.subject.keyword IBS-D
• dc.subject.keyword Irritable bowel syndrome
• dc.subject.keyword Serotonin type 3 receptor
• dc.title The serotonin receptor 3E variant is a risk factor for female IBS-D
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion