Yonsei Med J.  2015 Sep;56(5):1415-1420. 10.3349/ymj.2015.56.5.1415.

Association of 5-HT3B Receptor Gene Polymorphisms with the Efficacy of Ondansetron for Postoperative Nausea and Vomiting

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea. csho99@yuhs.ac
  • 2Department of Anesthesiology and Pain Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
Postoperative nausea and vomiting (PONV) is a common problem after general anesthesia. Although 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists have significantly reduced PONV, over 35% of patients treated with ondansetron can experience PONV. In this study, we investigated whether the Y129S and -100_-102AAG deletion polymorphisms of the 5-HT3B receptor gene affect the efficacy of ondansetron in preventing PONV.
MATERIALS AND METHODS
Two hundred and forty-five adult patients who underwent laparoscopic cholecystectomy were enrolled. Ondansetron 0.1 mg/kg was intravenously administered 30 minutes before the end of surgery. Genomic DNA was prepared from blood samples using a nucleic acid isolation device. Both the Y129S variant and the -100_-102AAG deletion variant were screened for using a single base primer extension assay and a DNA direct sequencing method, respectively. The relationship between genetic polymorphisms and clinical outcomes of ondansetron treatment was investigated.
RESULTS
Among the 5-HT3B AAG deletion genotypes, the incidence of PONV was higher in patients with the homomutant than with other genotypes during the first 2 hours after surgery (p=0.02). There were no significant differences in the incidence of PONV among genotypes at 2-24 hours after surgery. In the Y129S variants of the 5-HT3B receptor gene, there were no significant differences in the incidence of PONV among genotypes during the first 2 hours and at 2-24 hours after surgery.
CONCLUSION
The response to ondansetron for PONV was significantly influenced by the -100_-102AAG deletion polymorphisms of the 5-HT3B gene. Thus, the -100_-102AAG deletion variants may be a pharmacogenetic predictor for responsiveness to ondansetron for PONV.

Keyword

Postoperative nausea and vomiting; 5-HT3 receptor; ondansetron; genetic polymorphism

MeSH Terms

Adult
Aged
Anesthesia, General
Antiemetics/administration & dosage/*pharmacology
Cholecystectomy, Laparoscopic
Female
Genome, Human
Genotype
Humans
Incidence
Injections, Intravenous
Male
Middle Aged
Ondansetron/administration & dosage/*pharmacology
Polymorphism, Genetic
Postoperative Nausea and Vomiting/chemically induced/*drug therapy/epidemiology
Receptors, Serotonin, 5-HT3/*drug effects/*genetics
Time Factors
Antiemetics
Ondansetron
Receptors, Serotonin, 5-HT3

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