OBJECTIVES: Acute cytostatic drug induced nausea and vomiting is provoked by a release of endogenous serotonin that mediates its effect by binding to the 5-hydroxytryptamine type 3 (5-HT3) receptors. The most effective antiemetic drugs are the 5-HT3 receptor antagonists. Nevertheless about 30% of the patients do not respond satisfactorily. Five 5-HT3 receptor genes (5-HT(3A-E)) with high sequence homology have been identified. Two subunits, the 5-HT3A and 5-HT3B are expressed in anatomical structures known to be involved in the mechanism of acute cytostatic drug induced emesis. METHODS: We included 242 cancer patients at their first day of chemotherapy to investigate the influence of genetic polymorphisms of the 5-HT3A receptor gene on the intensity of nausea and vomiting which was documented using standardized interviews and visual analog scales. RESULTS: Sequencing of the entire 5-HT3A receptor gene of all patients revealed 21 polymorphisms, two of them were amino acid substitutions (Ala33Thr, Met257Ile). Linkage disequilibrium analysis revealed that 15 polymorphisms of the 5-HT3A receptor gene are partially linked to each other. However, none of the haplotypes was significantly associated with the intensity of cytostatic induced nausea and vomiting. CONCLUSION: Polymorphisms and haplotype analysis of the 5-HT3A receptor gene may not serve as a pharmacogenetic predictor of the antiemetic treatment with 5-HT3 receptor antagonists in cancer patients. Copyright 2004 Lippincott Williams & Wilkins
OBJECTIVES: Acute cytostatic drug induced nausea and vomiting is provoked by a release of endogenous serotonin that mediates its effect by binding to the 5-hydroxytryptamine type 3 (5-HT3) receptors. The most effective antiemetic drugs are the 5-HT3 receptor antagonists. Nevertheless about 30% of the patients do not respond satisfactorily. Five 5-HT3 receptor genes (5-HT(3A-E)) with high sequence homology have been identified. Two subunits, the 5-HT3A and 5-HT3B are expressed in anatomical structures known to be involved in the mechanism of acute cytostatic drug induced emesis. METHODS: We included 242 cancerpatients at their first day of chemotherapy to investigate the influence of genetic polymorphisms of the 5-HT3A receptor gene on the intensity of nausea and vomiting which was documented using standardized interviews and visual analog scales. RESULTS: Sequencing of the entire 5-HT3A receptor gene of all patients revealed 21 polymorphisms, two of them were amino acid substitutions (Ala33Thr, Met257Ile). Linkage disequilibrium analysis revealed that 15 polymorphisms of the 5-HT3A receptor gene are partially linked to each other. However, none of the haplotypes was significantly associated with the intensity of cytostatic induced nausea and vomiting. CONCLUSION: Polymorphisms and haplotype analysis of the 5-HT3A receptor gene may not serve as a pharmacogenetic predictor of the antiemetic treatment with 5-HT3 receptor antagonists in cancerpatients. Copyright 2004 Lippincott Williams & Wilkins
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