Association of 5-HT3B Receptor Gene Polymorphisms with the Efficacy of Ondansetron for Postoperative Nausea and Vomiting
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Purpose: Postoperative nausea and vomiting (PONV) is a common problem after general anesthesia. Although 5-hydroxytryptaminetype 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 geneticpolymorphisms 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 ondansetronfor PONV.
Abstract
Purpose: Postoperative nausea and vomiting (PONV) is a common problem after general anesthesia. Although 5-hydroxytryptaminetype 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 geneticpolymorphisms 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 ondansetronfor PONV.
참고문헌 (21)
- Candiotti KA, "The impact of pharmacogenomics on postoperative nausea and vomiting: do CYP2D6 allele copy number and polymorphisms affect the success or failure of ondansetron prophylaxis?", Anesthesiology, 102, pp.543~549 (2005)
- Lunn DV, "Low-dose droperidol reduces postoperative vomiting in paediatric day surgery", Br J Anaesth, 74, pp.509~511 (1995)
- Choi EM, "Association of ABCB1 polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting", Anaesthesia, 65, pp.996~1000 (2010)
- White H, "Randomized comparison of two anti-emetic strategies in high-risk patients undergoing day-case gynaecological surgery", Br J Anaesth, 98, pp.470~476 (2007)
- Bunce KT, "The role of 5-HT in postoperative nausea and vomiting", Br J Anaesth, 69(7 Suppl 1), pp.60S~62S (1992)
- Moon YE, "Anti-emetic effect of ondansetron and palonosetron in thyroidectomy: a prospective, randomized, double-blind study", Br J Anaesth, 108, pp.417~422 (2012)
- Kim SI, "Comparison of ramosetron with ondansetron for prevention of postoperative nausea and vomiting in patients undergoing gynaecological surgery", Br J Anaesth, 103, pp.549~553 (2009)
- Kaiser R, "Investigation of the association between 5-HT3A receptor gene polymorphisms and efficiency of antiemetic treatment with 5-HT3 receptor antagonists", Pharmacogenetics, 14, pp.271~278 (2004)
- Rueffert H, "Do variations in the 5-HT3A and 5-HT3B serotonin receptor genes (HTR3A and HTR3B) influence the occurrence of postoperative vomiting?", Anesth Analg, 109, pp.1442~1447 (2009)
- Janicki PK, "Genetic factors associated with pharmacotherapy and background sensitivity to postoperative and chemotherapy-induced nausea and vomiting", Exp Brain Res, 232, pp.2613~2625 (2014)
- Fasching PA, "Polymorphisms in the novel serotonin receptor subunit gene HTR3C show different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy", J Cancer Res Clin Oncol, 134, pp.1079~1086 (2008)
- Sugai T, "The effect of 5-hydroxytryptamine 3A and 3B receptor genes on nausea induced by paroxetine", Pharmacogenomics J, 6, pp.351~356 (2006)
- Tremblay PB, "Variations in the 5-hydroxytryptamine type 3B receptor gene as predictors of the efficacy of antiemetic treatment in cancer patients", J Clin Oncol, 21, pp.2147~2155 (2003)
- Kato M, "Effects of the serotonin type 2A, 3A and 3B receptor and the serotonin transporter genes on paroxetine and fluvoxamine efficacy and adverse drug reactions in depressed Japanese patients", Neuropsychobiology, 53, pp.186~195 (2006)
- Watcha MF, "Postoperative nausea and vomiting. Its etiology, treatment, and prevention", Anesthesiology, 77, pp.162~184 (1992)
- Krzywkowski K, "Do polymorphisms in the human 5-HT3 genes contribute to pathological phenotypes?", Biochem Soc Trans, 34(Pt 5), pp.872~876 (2006)
- Dubin AE, "The pharmacological and functional characteristics of the serotonin 5-HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit", J Biol Chem, 274, pp.30799~30810 (1999)
- Davies PA, "The 5-HT3B subunit is a major determinant of serotonin-receptor function", Nature, 397, pp.359~363 (1999)
- Frank B, "Investigation of the human serotonin receptor gene HTR3B in bipolar affective and schizophrenic patients", Am J Med Genet B Neuropsychiatr Genet, 131B, pp.1~5 (2004)
- Meineke C, "Functional characterization of a -100_-102delAAG deletion-insertion polymorphism in the promoter region of the HTR3B gene", Pharmacogenet Genomics, 18, pp.219~230 (2008)
- Apfel CC, "A simplified risk score for predicting postoperative nausea and vomiting:conclusions from cross-validations between two centers", Anesthesiology, 91, pp.693~700 (1999)