Investigation of HTR3C mutations for association with 5HT(3) receptor antagonist anti-emetic efficacy.
OBJECTIVE
Chemotherapy-induced nausea and vomiting is a significant clinical problem. The 5HT(3) receptor antagonists are effective anti-emetic medications but approximately 30% of patients do not respond.


METHODS
We examined the HTR3C gene, which is believed to encode a subunit of the 5HT(3) receptor, 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.


CONCLUSIONS
The results of this investigation indicate that the genetic variants that have been identified within HTR3C do not predict response to 5HT(3) antagonists, necessitating further investigation of possible genetic determinants of 5HT(3) antagonist efficacy.
Ward
Michael B
MB
Sansom Institute, University of South Australia, Frome Road, Adelaide, Australia. michael.ward@unisa.edu.au
Kotasek
Dusan
D
McKinnon
Ross A
RA
D000932:Antiemetics / Q000494:pharmacology* / Q000627:therapeutic use; D005787:Gene Frequency / Q000187:drug effects / Q000235:genetics; D014644:Genetic Variation / Q000187:drug effects / Q000235:genetics; D006239:Haplotypes / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000187:drug effects / Q000235:genetics*; D009325:Nausea / Q000235:genetics / Q000517:prevention & control; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D014839:Vomiting / Q000235:genetics / Q000517:prevention & control
D000932:Antiemetics; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists