Search

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-HT 3 AC 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., Competing Interests: Conflict-of-interest statement: APC Microbiome Ireland has conducted studies in collaboration with several 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., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)