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

Abstract

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.

A novel immune-related gene signature for diagnosis and potential immunotherapy of microsatellite stable endometrial carcinoma

“…In particular, the signal trasduction mechanism of 5-HT3 receptor is a ligand-gated ion channel (Na + /K + ), the binding of serotonin resulting in plasma membrane depolarization, whereas other 5-HT receptors are G protein-coupled receptors (GPCRs) and activated by cAMP. And 5-HT3 receptor had been proved to be positively expressed in lung cancer and colorectal carcinoma 19 , 20 . Schneider et al discovered that administration of antidepressants serotonin reuptake inhibitors (SSRIs) promoted the action of PD-1 checkpoint blockers and inhibited the tumor growth of untreatable pancreatic and colorectal cancers 21 .…”

Genetics of Functional Seizures; A Scoping Systematic Review

“…TPH2 has its most significant impact in the serotonin pathway. The study of somatization in other conditions often also points to serotonin [ 30 , 31 , 32 ]. A study showed increased methylation of the oxytocin receptor gene in 15 patients with motor functional neurological disorder compared with healthy controls [ 33 ].…”