Do variations in the 5-HT3A and 5-HT3B serotonin receptor genes (HTR3A and HTR3B) influence the occurrence of postoperative vomiting?
BACKGROUND
Postoperative nausea and vomiting are unpleasant side effects of general anesthesia. Besides known risk factors (female gender, nonsmoker, history, and opioids), a genetic influence of the serotonin receptor system on the development of nausea and vomiting has repeatedly been proposed. In this pilot study, we therefore investigated the genes of the serotonin receptor subunits A and B (HTR3A and HTR3B) for genetic variants.


METHODS
We included 95 patients who had suffered from postoperative vomiting (POV) after general anesthesia and 94 control patients. After DNA isolation, the entire HTR3A and HTR3B coding regions, the 5' flanking regions, and exon/intron boundaries were screened for genetic variants. Correlation of identified genetic variants with POV was determined by logistic regression.


RESULTS
We identified 16 different variants in the HTR3A gene and 19 in the HTR3B gene. By using a multivariate logistic regression model that also included classical risk factors, the HTR3A variant c1377A>G was associated with a significantly higher risk (odds ratio [OR] 2.972; 95% confidence interval [CI] 1.466-6.021; P = 0.003) and the HTR3B variants c5+201_+202delCA (OR 0.421; 95% CI 0.257-0.69; P = 0.001) and c6-137C>T (OR 0.034; 95% CI 0.003-0.332; P = 0.004) were associated with a lower risk for POV. However, all significant genetic variants were located in noncoding regions of their gene.


CONCLUSIONS
Genetic variations in the HTR3A and HTR3B gene seem to be associated with the individual risk of developing POV. How strong their influence is within the multifactorial genesis of POV needs to be investigated in additional studies with an appropriate sample size.
Rueffert
Henrik
H
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Leipzig, D-04103 Leipzig, Germany. henrik.rueffert@medizin.uni-leipzig.d
Thieme
Volker
V
Wallenborn
Jan
J
Lemnitz
Nicole
N
Bergmann
Astrid
A
Rudlof
Kristina
K
Wehner
Markus
M
Olthoff
Derk
D
Kaisers
Udo X
UX
D024506:5' Flanking Region; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D020250:Postoperative Nausea and Vomiting / Q000235:genetics*; D011985:Receptors, Serotonin / Q000235:genetics*; D044406:Receptors, Serotonin, 5-HT3; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
C509409:HTR3A protein, human; C509410:HTR3B protein, human; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3