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

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...

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Veröffentlicht in:WORLD JOURNAL OF GASTROENTEROLOGY 2022-06, Vol.28 (21), p.2334-2349
Hauptverfasser: Berens, Sabrina, Dong, Yuanjun, Fritz, Nikola, Walstab, Jutta, D'Amato, Mauro, Zheng, Tenghao, Wahl, Verena, Boekstegers, Felix, Bermejo, Justo Lorenzo, Martinez, Cristina, Schmitteckert, Stefanie, Clevers, Egbert, Engel, Felicitas, Gauss, Annika, Herzog, Wolfgang, Spiller, Robin, Goebel-Stengel, Miriam, Moennikes, Hubert, Andresen, Viola, Thomas, Frieling, Keller, Jutta, Pehl, Christian, Stein-Thoeringer, Christoph, Clarke, Gerard, Dinan, Timothy G, Quigley, Eamonn M, Sayuk, Gregory, Simren, Magnus, Tesarz, Jonas, Rappold, Gudrun, van Oudenhove, Lukas, Schaefert, Rainer, Niesler, Beate
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container_issue 21
container_start_page 2334
container_title WORLD JOURNAL OF GASTROENTEROLOGY
container_volume 28
creator Berens, Sabrina
Dong, Yuanjun
Fritz, Nikola
Walstab, Jutta
D'Amato, Mauro
Zheng, Tenghao
Wahl, Verena
Boekstegers, Felix
Bermejo, Justo Lorenzo
Martinez, Cristina
Schmitteckert, Stefanie
Clevers, Egbert
Engel, Felicitas
Gauss, Annika
Herzog, Wolfgang
Spiller, Robin
Goebel-Stengel, Miriam
Moennikes, Hubert
Andresen, Viola
Thomas, Frieling
Keller, Jutta
Pehl, Christian
Stein-Thoeringer, Christoph
Clarke, Gerard
Dinan, Timothy G
Quigley, Eamonn M
Sayuk, Gregory
Simren, Magnus
Tesarz, Jonas
Rappold, Gudrun
van Oudenhove, Lukas
Schaefert, Rainer
Niesler, Beate
description 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.
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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&gt;T, HTR3B c.386A&gt;C, HTR3C c.489C&gt;A, and HTR3E c.*76G&gt;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&gt;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&gt;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&gt;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.</description><identifier>ISSN: 1007-9327</identifier><language>eng</language><publisher>BAISHIDENG PUBLISHING GROUP INC</publisher><ispartof>WORLD JOURNAL OF GASTROENTEROLOGY, 2022-06, Vol.28 (21), p.2334-2349</ispartof><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,780,784,27860</link.rule.ids></links><search><creatorcontrib>Berens, Sabrina</creatorcontrib><creatorcontrib>Dong, Yuanjun</creatorcontrib><creatorcontrib>Fritz, Nikola</creatorcontrib><creatorcontrib>Walstab, Jutta</creatorcontrib><creatorcontrib>D'Amato, Mauro</creatorcontrib><creatorcontrib>Zheng, Tenghao</creatorcontrib><creatorcontrib>Wahl, Verena</creatorcontrib><creatorcontrib>Boekstegers, Felix</creatorcontrib><creatorcontrib>Bermejo, Justo Lorenzo</creatorcontrib><creatorcontrib>Martinez, Cristina</creatorcontrib><creatorcontrib>Schmitteckert, Stefanie</creatorcontrib><creatorcontrib>Clevers, Egbert</creatorcontrib><creatorcontrib>Engel, Felicitas</creatorcontrib><creatorcontrib>Gauss, Annika</creatorcontrib><creatorcontrib>Herzog, Wolfgang</creatorcontrib><creatorcontrib>Spiller, Robin</creatorcontrib><creatorcontrib>Goebel-Stengel, Miriam</creatorcontrib><creatorcontrib>Moennikes, Hubert</creatorcontrib><creatorcontrib>Andresen, Viola</creatorcontrib><creatorcontrib>Thomas, Frieling</creatorcontrib><creatorcontrib>Keller, Jutta</creatorcontrib><creatorcontrib>Pehl, Christian</creatorcontrib><creatorcontrib>Stein-Thoeringer, Christoph</creatorcontrib><creatorcontrib>Clarke, Gerard</creatorcontrib><creatorcontrib>Dinan, Timothy G</creatorcontrib><creatorcontrib>Quigley, Eamonn M</creatorcontrib><creatorcontrib>Sayuk, Gregory</creatorcontrib><creatorcontrib>Simren, Magnus</creatorcontrib><creatorcontrib>Tesarz, Jonas</creatorcontrib><creatorcontrib>Rappold, Gudrun</creatorcontrib><creatorcontrib>van Oudenhove, Lukas</creatorcontrib><creatorcontrib>Schaefert, Rainer</creatorcontrib><creatorcontrib>Niesler, Beate</creatorcontrib><title>Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study</title><title>WORLD JOURNAL OF GASTROENTEROLOGY</title><description>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&gt;T, HTR3B c.386A&gt;C, HTR3C c.489C&gt;A, and HTR3E c.*76G&gt;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&gt;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&gt;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&gt;A is involved in depressive and anxiety symptoms in individuals with IBS. 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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&gt;T, HTR3B c.386A&gt;C, HTR3C c.489C&gt;A, and HTR3E c.*76G&gt;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&gt;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&gt;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&gt;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.</abstract><pub>BAISHIDENG PUBLISHING GROUP INC</pub><oa>free_for_read</oa></addata></record>
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title Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study
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