Investigation of HTR3C mutations for association with 5HT3 receptor antagonist anti-emetic efficacy
Abstract
Objective: Chemotherapy-induced nausea and vomiting is a significant clinical problem. The 5HT3 receptor antagonists are effective anti-emetic medications but approximately 30% of patients do not respond. Method: We examined the HTR3C gene, which is believed to encode a subunit of the 5HT3receptor, for genetic variation and association with anti-emetic efficacy in a group of 70 patients receiving cancer chemotherapy. Results: Seven novel mutations were identified; three mutations resulted in amino acid substitutions, two were synonymous and two were intronic. No statistically significant associations between either isolated mutations or estimated haplotypes and anti-emetic efficacy were detected. Conclusion: The results of this investigation indicate that the genetic variants that have been identified within HTR3C do not predict response to 5HT3antagonists, necessitating further investigation of possible genetic determinants of 5HT3antagonist efficacy.
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