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

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 

机构地区：[1]Department of General Internal Medicine and Psychosomatics,University Hospital Heidelberg,Heidelberg 69120,Germany [2]Department of Human Molecular Genetics,Institute of Human Genetics,University of Heidelberg,Heidelberg 69120,Germany [3]Department of General Internal Medicine and Psychosomatics,Internal Medicine II,University Hospital Heidelberg,Heidelberg 69120,Germany [4]Department of Human Molecular Genetics,University of Heidelberg,Heidelberg 69120,Germany [5]Gastrointestinal Genetics Lab,CIC bioGUNE-BRTA,Derio 48160,Spain [6]IKERBASQUE,Basque Foundation for Science,Bilbao 48001,Spain [7]Unit of Clinical Epidemiology,Department of Medicine Solna,Karolinska Institutet,Stockholm 17177,Sweden [8]Institute of Medical Biometry and Informatics,Heidelberg University,Heidelberg 69120,Germany [9]Lleida Institute for Biomedical Research Dr.PifarréFoundation(IRBLleida),Av.Alcalde Rovira Roure,Lleida 25198,Spain [10]Department of Clinical and Experimental Medicine,Translational Research Center for Gastrointestinal Disorders,KU Leuven,Leuven 3000,Belgium [11]Department of Gastroenterology,Infectious Diseases and Intoxications,University of Heidelberg,Heidelberg 69120,Germany [12]Department of General Internal Medicine and Psychosomatics,Heidelberg University,Heidelberg 69120,Germany [13]Nottingham Digestive Diseases Centre,University of Nottingham,Nottingham NG72QL,United Kingdom [14]Helios Klinikum Rottweil,Rottweil 78628,Germany [15]Department of Medicine,Institute of Neurogastroenterology(H.M.),Martin-Luther-Hospital,Belin 14193,Germany [16]Israelitisches Krankenhaus in Hamburg,Hamburg 22297,Germany [17]Internal Medicine II,Helios Klinikum Krefeld,Krefeld 47805,Germany [18]Israelitisches Krankenhaus Hamburg,Hamburg 22297,Ghana [19]Krankenhaus Vilsbiburg,Vilsbiburg 84137,Germany [20]Division of Microbiome and Cancer,German Cancer Research Center(DKFZ),Heidelberg 69120,Germany [21]Department of Psychiatry and Neurobehavioral Science,University College Cork,Cork T23,Ireland [22]Medicine in Digestive Disorders,Departm

出　　处：《World Journal of Gastroenterology》2022年第21期2334-2349,共16页世界胃肠病学杂志（英文版）

基　　金：results in part from collaboration and network activities promoted under the frame of the international network GENIEUR (Genes in Irritable Bowel Syndrome Research Network Europe),which has been funded by the COST program (BM1106, www.GENIEUR.eu);currently supported by the European Society of Neurogastroenterology and Motility (ESNM, www.ESNM.eu)

摘　　要：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 IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four 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 models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS 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 IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The 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 

分 类 号：R574[医药卫生—消化系统]