The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome
5-HT; IBS; Transportador de serotonina
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Departament de Salut de la Generalitat de Catalunya (DS) |
| Repositorio: | Scientia. Dipòsit d'Informació Digital del Departament de Salut |
| OAI Identifier: | oai:scientiasalut.gencat.cat:11351/7233 |
| Acceso en línea: | https://hdl.handle.net/11351/7233 |
| Access Level: | acceso abierto |
| Palabra clave: | Còlon irritable - Fisiologia patològica Serotonina - Metabolisme DISEASES::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colonic Diseases, Functional::Irritable Bowel Syndrome CHEMICALS AND DRUGS::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Tryptamines::Serotonin Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedades del colon::enfermedades funcionales del colon::síndrome del colon irritable COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::triptaminas::serotonina Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
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The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndromeMohr, SandraFritz, NikolaHammer, ChristianMartínez, CristinaBerens, SabrinaSchmitteckert, StefanieSantos Vicente, Fco JavierVicario Perez, MariaCòlon irritable - Fisiologia patològicaSerotonina - MetabolismeDISEASES::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colonic Diseases, Functional::Irritable Bowel SyndromeCHEMICALS AND DRUGS::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Tryptamines::SerotoninOther subheadings::Other subheadings::Other subheadings::/metabolismENFERMEDADES::enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedades del colon::enfermedades funcionales del colon::síndrome del colon irritableCOMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::triptaminas::serotoninaOtros calificadores::Otros calificadores::Otros calificadores::/metabolismo5-HT; IBS; Transportador de serotonina5-HT; IBS; Transportador de serotonina5-HT; IBS; Serotonin transporterIrritable 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.WileyInstitut Català de la Salut[Mohr S, Fritz N, Schmitteckert S] Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany. [Hammer C] Department of Cancer Immunology, Genentech, South San Francisco, CA, USA. Department of Human Genetics, Genentech, South San Francisco, CA, USA. [Martínez C] Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany. Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain. Lleida Institute for Biomedical Research, Dr. Pifarré Foundation (IRBLleida), Lleida, Spain. [Berens S] Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany. [Vicario M, Santos J] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202220222021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/7233Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésJournal of Cellular and Molecular Medicine;25(16)https://doi.org/10.1111/jcmm.16736Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/72332026-06-12T09:38:37Z |
| dc.title.none.fl_str_mv |
The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome |
| title |
The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome |
| spellingShingle |
The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome Mohr, Sandra Còlon irritable - Fisiologia patològica Serotonina - Metabolisme DISEASES::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colonic Diseases, Functional::Irritable Bowel Syndrome CHEMICALS AND DRUGS::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Tryptamines::Serotonin Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedades del colon::enfermedades funcionales del colon::síndrome del colon irritable COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::triptaminas::serotonina Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
| title_short |
The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome |
| title_full |
The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome |
| title_fullStr |
The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome |
| title_full_unstemmed |
The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome |
| title_sort |
The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome |
| dc.creator.none.fl_str_mv |
Mohr, Sandra Fritz, Nikola Hammer, Christian Martínez, Cristina Berens, Sabrina Schmitteckert, Stefanie Santos Vicente, Fco Javier Vicario Perez, Maria |
| author |
Mohr, Sandra |
| author_facet |
Mohr, Sandra Fritz, Nikola Hammer, Christian Martínez, Cristina Berens, Sabrina Schmitteckert, Stefanie Santos Vicente, Fco Javier Vicario Perez, Maria |
| author_role |
author |
| author2 |
Fritz, Nikola Hammer, Christian Martínez, Cristina Berens, Sabrina Schmitteckert, Stefanie Santos Vicente, Fco Javier Vicario Perez, Maria |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
Institut Català de la Salut [Mohr S, Fritz N, Schmitteckert S] Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany. [Hammer C] Department of Cancer Immunology, Genentech, South San Francisco, CA, USA. Department of Human Genetics, Genentech, South San Francisco, CA, USA. [Martínez C] Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany. Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain. Lleida Institute for Biomedical Research, Dr. Pifarré Foundation (IRBLleida), Lleida, Spain. [Berens S] Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany. [Vicario M, Santos J] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus |
| dc.subject.none.fl_str_mv |
Còlon irritable - Fisiologia patològica Serotonina - Metabolisme DISEASES::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colonic Diseases, Functional::Irritable Bowel Syndrome CHEMICALS AND DRUGS::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Tryptamines::Serotonin Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedades del colon::enfermedades funcionales del colon::síndrome del colon irritable COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::triptaminas::serotonina Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
| topic |
Còlon irritable - Fisiologia patològica Serotonina - Metabolisme DISEASES::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colonic Diseases, Functional::Irritable Bowel Syndrome CHEMICALS AND DRUGS::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Tryptamines::Serotonin Other subheadings::Other subheadings::Other subheadings::/metabolism ENFERMEDADES::enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedades del colon::enfermedades funcionales del colon::síndrome del colon irritable COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::triptaminas::serotonina Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo |
| description |
5-HT; IBS; Transportador de serotonina |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2022 2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/11351/7233 |
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https://hdl.handle.net/11351/7233 |
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Inglés |
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Inglés |
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Journal of Cellular and Molecular Medicine;25(16) https://doi.org/10.1111/jcmm.16736 |
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Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf application/pdf |
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Wiley |
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Wiley |
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Scientia reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut instname:Departament de Salut de la Generalitat de Catalunya (DS) |
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Departament de Salut de la Generalitat de Catalunya (DS) |
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Scientia. Dipòsit d'Informació Digital del Departament de Salut |
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Scientia. Dipòsit d'Informació Digital del Departament de Salut |
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15,81155 |