TY - JOUR
T1 - Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome
T2 - A multicenter retrospective study
AU - Berens, Sabrina
AU - Dong, Yuanjun
AU - Fritz, Nikola
AU - Walstab, Jutta
AU - D'Amato, Mauro
AU - Zheng, Tenghao
AU - Wahl, Verena
AU - Boekstegers, Felix
AU - Bermejo, Justo Lorenzo
AU - Martinez, Cristina
AU - Schmitteckert, Stefanie
AU - Clevers, Egbert
AU - Engel, Felicitas
AU - Gauss, Annika
AU - Herzog, Wolfgang
AU - Spiller, Robin
AU - Goebel-Stengel, Miriam
AU - Mönnikes, Hubert
AU - Andresen, Viola
AU - Thomas, Frieling
AU - Keller, Jutta
AU - Pehl, Christian
AU - Stein-Thöringer, Christoph
AU - Clarke, Gerard
AU - Dinan, Timothy G.
AU - Quigley, Eamonn M.
AU - Sayuk, Gregory
AU - Simrén, Magnus
AU - Tesarz, Jonas
AU - Rappold, Gudrun
AU - van Oudenhove, Lukas
AU - Schaefert, Rainer
AU - Niesler, Beate
N1 - Funding Information:
We would like to thank all patients for their participation in this study and the supporting staff at each site. We acknowledge the kind support of Bartram CR and Hinderhofer K. We would also thank Startt B for proofreading and Bacon C for editing the manuscript. This manuscript 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) and is currently supported by the European Society of Neurogastroen-terology and Motility (ESNM, www.ESNM.eu).
Funding Information:
companies, including GSK, Pfizer, Cremo, Suntory, Wyeth, Mead Johnson, Nutricia, 4D Pharma, and DuPont. Dinan TG has been an invited speaker at meetings organized by Servier, Lundbeck, Janssen, and AstraZeneca and has received research funding from Mead Johnson, Cremo, Suntory Wellness, Nutricia, and 4D Pharma. Clarke G has been an invited speaker at meetings organized by Janssen and is receipt of research funding from Pharmavite. The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this report.
Publisher Copyright:
© The Author(s) 2022.
PY - 2022/6/7
Y1 - 2022/6/7
N2 - 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 (Fdepressive = 7.475, Pdepressive = 0.006; Fanxiety = 6.535, Panxiety = 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.
AB - 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 (Fdepressive = 7.475, Pdepressive = 0.006; Fanxiety = 6.535, Panxiety = 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.
KW - 5-HT3 receptor subunit gene polymorphisms
KW - Anxiety
KW - Depression
KW - Irritable bowel syndrome
KW - Single-nucleotide polymorphism score
KW - Somatization
UR - http://www.scopus.com/inward/record.url?scp=85131404201&partnerID=8YFLogxK
U2 - 10.3748/wjg.v28.i21.2334
DO - 10.3748/wjg.v28.i21.2334
M3 - Article
C2 - 35800179
AN - SCOPUS:85131404201
SN - 1007-9327
VL - 28
SP - 2334
EP - 2349
JO - World Journal of Gastroenterology
JF - World Journal of Gastroenterology
IS - 21
ER -