Serotonin Receptors Polymorphisms Are Associated With Cyclic Vomiting Syndrome

Background: Cyclic vomiting syndrome (CVS) is a disorder characterized by sudden, recurrent episodes of severe nausea and vomiting. The pathophysiology of CVS is not known but genetic factors that regulate emetic neurocircuitry have been proposed. The aim of this study was to investigate whether different variations in genes encoding serotonin receptors (HTRs) are associated with susceptibility to CVS and/or CVS symptoms. Methods: This case-control study included 70 patients with CVS:16 male and 54 female, and 2504 healthy controls from the 1000 Genomes Project database. Single-nucleotide polymorphisms (SNPs) in genes encoding serotonin receptors (HTR1B, HTR1D, HTR3B and HTR3C) and correlations between SNPs and the symptoms of CVS were determined. Key Results: Our study discovered that patients with GG, AA and GG genotypes of HTR1B/D rs6296, rs6298 and rs6300, respectively, as well as the CC genotype of HTR3B rs176744 are associated with an increased risk (p < 0.001), whereas allele C in rs3788987 (HTR3B, p < 0.01) and allele A in rs6766410 (HTR3C, p < 0.05) were associated with a decreased risk of CVS. In addition, statistical analysis indicated that CVS patients with GA or AA genotypes of HTR1D rs676643 gene have a seven-fold increase in risk of depression compared to patients with GG genotype (p < 0.01). Conclusions and Inferences: Our study revealed for the first time that variations in 5-HTR genes may contribute to CVS susceptibility and CVS-related symptoms.