Citations 2
The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome
Mohr, Sandra , Fritz, Nikola, Hammer, Christian , Martínez, Cristina , Berens, Sabrina , Schmitteckert, Stefanie , Wahl, Verena, Schmidt, Målin , Houghton, Lesley A. , Goebel‐Stengel, Miriam , Kabisch, Maria, Götze, Dorothea, Milovač, Irina , D’Amato, Mauro , Röth, Ralph , Mönnikes, Hubert, Engel, Felicitas , Gauss, Annika , Tesarz, Jonas , Raithel, Martin , Andresen, Viola , Frieling, Thomas , Pehl, Christian, Stein‐Thöringer, Christoph, Clarke, Gerard , Kennedy, Paul J. , Cryan, John F. , Spiller, Robert E. , Beltrán, Caroll J. , Madrid, Ana María , Torres, Verónica , Arce, Edith Pérez de , Herzog, Wolfgang , Sayuk, Gregory S. , Karamanolis, George, Pojskić, Lejla , Bustamante, Mariona , Rabionet, Raquel , Estivil, Xavier, Wouters, Mira M. , Rappold, Gudrun , Santos, Javier , Schaefert, Rainer , Niesler, Beate , Zheng, Tenghao , Engel, Felicitas , Gauss, Annika , Tesarz, Jonas , Raithel, Martin , Andresen, Viola , Frieling, Thomas , Keller, Jutta , Stein-Thöringer, Christoph , Clarke, Gerard , Kennedy, Paul J , Cryan, John F , Dinan, Timothy G , Quigley, Eamonn M M , Spiller, Robin , Madrid, Ana María , Pérez de Arce, Edith , Herzog, Wolfgang , Mayer, Emeran A , Sayuk, Gregory , Gazouli, Maria , Karamanolis, George , Kapur-Pojskič, Lejla , Bustamante, Mariona , Rabionet, Raquel , Estivil, Xavier , Franke, André , Lieb, Wolfgang , Boeckxstaens, Guy , Wouters, Mira M , Simrén, Magnus , Rappold, Gudrun A , Vicario, Maria , Santos, Javier , Schaefert, Rainer , Lorenzo-Bermejo, Justo , Niesler, Beate , D'Amato, Mauro , Houghton, L A , Martínez, Cristina , Zheng, Tenghao , Stein-Thöringer, Christoph K., Quigley, Eamonn M.M. , Torres, Verónica, Boeckxstaens, Guy E. , Simrén, Magnus , Bermejo, Justo Lorenzo
Journal of Cellular and Molecular Medicine | June 24, 2021 | Volume: 25 | Issue: 16 | Pages: 8047-8061
AbstractIrritable bowel syndrome (IBS) is a gut‐brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation‐predominant IBS (IBS‐C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta‐analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS‐C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow‐up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS‐C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.
The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function
Carrington, Emma V. , Heinrich, Henriette , Knowles, Charles H. , Fox, Mark , Rao, Satish S.C. , Altomare, Donato F. , Bharucha, Adil E. , Burgell, Rebecca , Chey, William D. , Chiarioni, Guiseppe, Dinning, Phil G. , Emmanuel, Anton , Felt‐Bersma, R. J. F. , Malcolm, Allison , Mittal, Ravinder K., Mion, François , O’Connell, P. R. , Pehl, Christian, Reveille, R. Matthew, Vaizey, C. J. , Vitton, Véronique , Whitehead, William E. , Scott, S. Mark , Group, All members of the International Anorectal Physiology Working, Rao, Satish , Jung, Kee Wook , Lembo, Anthony , Mittal, Ravinder K , Vitton, Veronique , Whitehead, W E , Farouk, Ridzuan , Jung, Kee Wook , Lembo, Anthony , Myung, Seung‐Jae , Remes Troche, José M , Wong, Reuben K. , Group, All members of the International Anorectal Physiology Working, Malcolm, Allison
Neurogastroenterology & Motility | August 12, 2019 | Volume: 32 | Issue: 1 | Pages: No page available
Abstract Background This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high‐resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. Methods Twenty‐nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face‐to‐face and three remote meetings to derive consensus between 2014 and 2018. Key recommendations The IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia. Conclusions and Inferences This framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much‐needed standardization to these techniques.