The serotonin receptor 3E variant is a risk factor for female IBS-D Article Swipe
Nikola Fritz
,
Sabrina Berens
,
Yuanjun Dong
,
Cristina Martínez
,
Stefanie Schmitteckert
,
Lesley A. Houghton
,
Miriam Goebel‐Stengel
,
Verena Wahl
,
Maria Kabisch
,
Dorothea Götze
,
Mauro D’Amato
,
Tenghao Zheng
,
Ralph Röth
,
Hubert Mönnikes
,
Jonas Tesarz
,
Felicitas Engel
,
Annika Gauss
,
Martin Raithel
,
Viola Andresen
,
Jutta Keller
,
Thomas Frieling
,
Christian Pehl
,
Christoph Stein-Thöringer
,
Gerard Clarke
,
Paul J. Kennedy
,
John F. Cryan
,
Timothy G. Dinan
,
Eamonn M.M. Quigley
,
Robert E. Spiller
,
Caroll J. Beltrán
,
Ana María Madrid
,
Verónica Torres
,
Emeran A. Mayer
,
Gregory S. Sayuk
,
Maria Gazouli
,
George Karamanolis
,
Mariona Bustamante
,
Xavier Estivil
,
Raquel Rabionet
,
Per Hoffmann
,
Markus M. Nöthen
,
Stefanie Heilmann‐Heimbach
,
Börge Schmidt
,
André Franke
,
Wolfgang Lieb
,
Wolfgang Herzog
,
Guy E. Boeckxstaens
,
Mira M. Wouters
,
Magnus Simrén
,
Gudrun Rappold
,
María Vicario
,
Javier Santos
,
Rainer Schaefert
,
Justo Lorenzo Bermejo
,
Beate Niesler
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1007/s00109-022-02244-w
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1007/s00109-022-02244-w
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.
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- Type
- review
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- en
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- https://doi.org/10.1007/s00109-022-02244-w
- https://link.springer.com/content/pdf/10.1007/s00109-022-02244-w.pdf
- OA Status
- hybrid
- Cited By
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- References
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- Related Works
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- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4296322556Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1007/s00109-022-02244-wDigital Object Identifier
- Title
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The serotonin receptor 3E variant is a risk factor for female IBS-DWork title
- Type
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reviewOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-09-19Full publication date if available
- Authors
-
Nikola Fritz, Sabrina Berens, Yuanjun Dong, Cristina Martínez, Stefanie Schmitteckert, Lesley A. Houghton, Miriam Goebel‐Stengel, Verena Wahl, Maria Kabisch, Dorothea Götze, Mauro D’Amato, Tenghao Zheng, Ralph Röth, Hubert Mönnikes, Jonas Tesarz, Felicitas Engel, Annika Gauss, Martin Raithel, Viola Andresen, Jutta Keller, Thomas Frieling, Christian Pehl, Christoph Stein-Thöringer, Gerard Clarke, Paul J. Kennedy, John F. Cryan, Timothy G. Dinan, Eamonn M.M. Quigley, Robert E. Spiller, Caroll J. Beltrán, Ana María Madrid, Verónica Torres, Emeran A. Mayer, Gregory S. Sayuk, Maria Gazouli, George Karamanolis, Mariona Bustamante, Xavier Estivil, Raquel Rabionet, Per Hoffmann, Markus M. Nöthen, Stefanie Heilmann‐Heimbach, Börge Schmidt, André Franke, Wolfgang Lieb, Wolfgang Herzog, Guy E. Boeckxstaens, Mira M. Wouters, Magnus Simrén, Gudrun Rappold, María Vicario, Javier Santos, Rainer Schaefert, Justo Lorenzo Bermejo, Beate NieslerList of authors in order
- Landing page
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https://link.springer.com/content/pdf/10.1007/s00109-022-02244-w.pdfDirect link to full text PDF
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
- OA URL
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https://link.springer.com/content/pdf/10.1007/s00109-022-02244-w.pdfDirect OA link when available
- Concepts
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Irritable bowel syndrome, Internal medicine, Gastroenterology, Medicine, Context (archaeology), Endocrinology, Biology, PaleontologyTop concepts (fields/topics) attached by OpenAlex
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6Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 3, 2023: 1Per-year citation counts (last 5 years)
- References (count)
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44Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| primary_location.raw_source_name | Journal of Molecular Medicine |
| primary_location.landing_page_url | https://doi.org/10.1007/s00109-022-02244-w |
| publication_date | 2022-09-19 |
| publication_year | 2022 |
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