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Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome:A multicenter retrospective study

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World Journal of Gastroenterology 2022年第21期28卷 2334-2349页

作者： Sabrina Berens Yuanjun Dong Nikola Fritz Jutta Walstab Mauro D'Amato Tenghao Zheng Verena Wahl felix boekstegers Justo Lorenzo Bermejo Cristina Martinez Stefanie Schmitteckert Egbert Clevers Felicitas Engel Annika Gauss Wolfgang Herzog Robin Spiller Miriam Goebel-Stengel Hubert Mönnikes Viola Andresen Frieling Thomas Jutta Keller Christian Pehl Christoph Stein-Thöringer Gerard Clarke Timothy G Dinan Eamonn M Quigley Gregory Sayuk Magnus Simrén Jonas Tesarz Gudrun Rappold Lukas van Oudenhove Rainer Schaefert Beate Niesler Department of General Internal Medicine and Psychosomatics University Hospital HeidelbergHeidelberg 69120Germany Department of Human Molecular Genetics Institute of Human GeneticsUniversity of HeidelbergHeidelberg 69120Germany Department of General Internal Medicine and Psychosomatics Internal Medicine IIUniversity Hospital HeidelbergHeidelberg 69120Germany Department of Human Molecular Genetics University of HeidelbergHeidelberg 69120Germany Gastrointestinal Genetics Lab CIC bioGUNE-BRTADerio 48160Spain IKERBASQUE Basque Foundation for ScienceBilbao 48001Spain Unit of Clinical Epidemiology Department of Medicine SolnaKarolinska InstitutetStockholm 17177Sweden Institute of Medical Biometry and Informatics Heidelberg UniversityHeidelberg 69120Germany Lleida Institute for Biomedical Research Dr.PifarréFoundation(IRBLleida) Av.Alcalde Rovira RoureLleida 25198Spain Department of Clinical and Experimental Medicine Translational Research Center for Gastrointestinal DisordersKU LeuvenLeuven 3000Belgium Department of Gastroenterology Infectious Diseases and IntoxicationsUniversity of HeidelbergHeidelberg 69120Germany Department of General Internal Medicine and Psychosomatics Heidelberg UniversityHeidelberg 69120Germany Nottingham Digestive Diseases Centre University of NottinghamNottingham NG72QLUnited Kingdom Helios Klinikum Rottweil Rottweil 78628Germany Department of Medicine Institute of Neurogastroenterology(H.M.)Martin-Luther-HospitalBelin 14193Germany Israelitisches Krankenhaus in Hamburg Hamburg 22297Germany Internal Medicine II Helios Klinikum KrefeldKrefeld 47805Germany Israelitisches Krankenhaus Hamburg Hamburg 22297Ghana Krankenhaus Vilsbiburg Vilsbiburg 84137Germany Division of Microbiome and Cancer German Cancer Research Center(DKFZ)Heidelberg 69120Germany Department of Psychiatry and Neurobehavioral Science University College CorkCork T23Ireland Medicine in Digestive Disorders Department of MedicineLynda K.and David M.Underwood Center for Digestive DisordersHou

BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with *** In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and ***,anxiety,and somatization symptoms and sociodemographic characteristics were *** functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive *** also performed separate analyses for sex and IBS *** scores were calculated as the number of minor alleles of the SNPs *** impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx *** Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in *** potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant *** We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with *** SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.

关键词： Irritable bowel syndrome 5-HT3 receptor subunit gene polymorphisms Single-nucleotide polymorphism score Depression Anxiety Somatization

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