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  • Fritz, N. (author)

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

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-09-19
  • Springer Science and Business Media LLC,2022

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/321216
  • https://gup.ub.gu.se/publication/321216URI
  • https://doi.org/10.1007/s00109-022-02244-wDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:150779665URI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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-HT(3)Rs 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.

Subject headings and genre

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  • Berens, S. (author)
  • Dong, Y. J. (author)
  • Martinez, C. (author)
  • Schmitteckert, S. (author)
  • Houghton, L. A. (author)
  • Goebel-Stengel, M. (author)
  • Wahl, V. (author)
  • Kabisch, M. (author)
  • Gotze, D. (author)
  • D'Amato, M. (author)
  • Zheng, T. H. (author)
  • Roth, R. (author)
  • Monnikes, H. (author)
  • Tesarz, J. (author)
  • Engel, F. (author)
  • Gauss, A. (author)
  • Raithel, M. (author)
  • Andresen, V. (author)
  • Keller, J. (author)
  • Frieling, T. (author)
  • Pehl, C. (author)
  • Stein-Thoringer, C. (author)
  • Clarke, G. (author)
  • Kennedy, P. J. (author)
  • Cryan, J. F. (author)
  • Dinan, T. G. (author)
  • Quigley, E. M. M. (author)
  • Spiller, R. (author)
  • Beltran, C. (author)
  • Madrid, A. M. (author)
  • Torres, V. (author)
  • Mayer, E. A. (author)
  • Sayuk, G. (author)
  • Gazouli, M. (author)
  • Karamanolis, G. (author)
  • Bustamante, M. (author)
  • Estivil, X. (author)
  • Rabionet, R. (author)
  • Hoffmann, P. (author)
  • Nothen, M. M. (author)
  • Heilmann-Heimbach, S. (author)
  • Schmidt, B. (author)
  • Franke, A. (author)
  • Lieb, W. (author)
  • Herzog, W. (author)
  • Boeckxstaens, G. (author)
  • Wouters, M. M. (author)
  • Simrén, Magnus,1966Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine(Swepub:gu)xsimrm (author)
  • Rappold, G. A. (author)
  • Vicario, M. (author)
  • Santos, J. (author)
  • Schaefert, R. (author)
  • Lorenzo-Bermejo, J. (author)
  • Niesler, B. (author)
  • Göteborgs universitetInstitutionen för medicin (creator_code:org_t)

Related titles

  • In:Journal of Molecular Medicine-Jmm: Springer Science and Business Media LLC100:11, s. 1617-16270946-27161432-1440

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