The Human Serotonin Type 3 Receptor Gene (HTR3A-E) Allelic Variant Database

Abstract

Serotonin type 3 (5-HT ) receptors are ligand-gated ion channels formed by five subunits (5-HT3A-E), which are encoded by the HTR3A, HTR3B, HTR3C, HTR3D, and HTR3E genes. Functional receptors are pentameric complexes of diverse composition. Different receptor subtypes confer a predisposition to nausea and vomiting during chemotherapy, pregnancy, and following surgery. In addition, different subtypes contribute to neurogastroenterologic disorders such irritable bowel syndrome (IBS) and eating disorders as well as comorbid psychiatric conditions. 5-HT receptor antagonists are established treatments for emesis and IBS and are beneficial in the treatment of psychiatric diseases. Several case-control and pharmacogenetic studies have demonstrated an association between HTR3 variants and psychiatric and neurogastroenterologic phenotypes. Recently, their potential as predictors of nausea and vomiting and treatment of psychiatric disorders became evident. This information is now available in the serotonin receptor 3 HTR3 gene allelic variant database (www.htr3.uni-hd.de), which contains five sub-databases, one for each of the five different serotonin receptor genes HTR3A-E. Information on HTR3 variants, their functional relevance, associated phenotypes, and pharmacogenetic data such as drug response and side effects are available. This central information pool should help clinicians as well as scientists to evaluate their findings and to use the relevant information for subsequent genotype-phenotype correlation studies and pharmacogenetic approaches.

Editorial: understanding differences in patient response to ondansetron in irritable bowel syndrome with diarrhoea—are we any closer?

“…Stool consistency responders were more likely to carry the CC genotype (SNP p.N163K rs6766410) of the HTR3C gene encoding the 3C subunit of the 5‐HT 3 receptor, although the implications of this are unclear. Despite genes encoding subunits HTR3A, HTR3B, and HTR3E having shown an association with IBS‐D previously, no associations were detected in this study.…”

Uncovering the pathophysiology of irritable bowel syndrome by exploring the gut-brain axis: a narrative review

“…For instance, 5-HT3 receptor antagonists have been used. However, the 5-HT3 receptor genes are polymorphic, and these variants are thought to affect the treatment response (85). The roles of the different 5-HT3 receptor variants are now detailed in an electronic database (85), which allows genetic and pharmacogenetic data to be continuously gathered as a reference for potential clinical use.…”

Pharmacogenetics and the Treatment of Functional Gastrointestinal Disorders

“…Serotonin receptors are therapeutic targets in IBS, such as with the use of 5-HT 3 receptor antagonists in IBS-D and 5-HT 4 agonists in IBS-C or functional constipation. In addition to the influence of 5-HTTLPR on SERT function, the genes for 5-HT 3 receptors are also polymorphic, and these variants are thought to affect the response to treatment [58].…”

“…To date, no trials have studied the effects of such 5-HT 3B receptor polymorphisms on responses to drugs in FGIDs. Celli et al summarized the role of the different 5-HT 3 receptor variants (CHTRA-E), provided an electronic database where genetic and pharmacogenetic data will be gathered as a reference for potential clinical use, and postulated that polymorphisms in 5-HT 3 receptor genes may have clinical utility in the management of FGIDs [58].…”