The female-specific effect of 5-hydroxytryptamine receptor 3A gene on postoperative vomiting in Taiwan

Abstract Postoperative vomiting (POV) is a common complication after general anesthesia. Clarifying the genetic factors that affect POV are important for evaluating a patient's susceptibility to the condition. Although evidence suggests that the 5-hydroxytryptamine (serotonin) receptor 3A ( HTR3A ) gene may be important in the occurrence of POV, associations for HTR3A polymorphisms with POV have not been investigated in a Taiwanese population. Three single nucleotide polymorphisms (SNPs) of the HTR3A gene were used to study the genetic association with POV in 369 postoperative Taiwanese adults who underwent general anesthesia. Although no significant differences were found at the single-locus level for HTR3A polymorphisms, a significant haplotype-based association was found between HTR3A and POV. In addition, because female sex is associated with a higher risk of PONV (postoperative nausea and vomiting), we separately analyzed the haplotypic associations for both sexes to test whether HTR3A genetic factors interact with female sex and specifically contribute to the etiology of POV. We found that a significant haplotype effect was identified only for females. The CTT haplotype, the most common, showed a significant protective effect (odds ratio: 0.68), and the CTG haplotype was associated with a significantly higher risk (odds ratio: 2.08) for POV in females. Furthermore, p values from an overall comparison of all haplotypes and from permutation tests were still significant. These data suggest that the HTR3A gene may have a sex-specific effect on the etiology of POV in Taiwan. The effects and the biological causal variants related to POV are worth additional investigation.