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A serotonin transporter polymorphism is associated with postoperative nausea and vomiting

An observational study in two different patient cohorts

Stamer, Ulrike M.; Schmutz, Maxime; Wen, Tingting; Banz, Vanessa; Lippuner, Christoph; Zhang, Lan; Steffens, Michael; Stüber, Frank

European Journal of Anaesthesiology (EJA): August 2019 - Volume 36 - Issue 8 - p 566–574
doi: 10.1097/EJA.0000000000001014
Postoperative nausea and vomiting
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BACKGROUND Clinical risk factors for postoperative nausea and vomiting (PONV) are well described, whereas genetic findings are conflicting.

OBJECTIVE The aim of this study was to investigate a possible association of genetic variants and nongenetic variables with the incidence and severity of PONV.

DESIGN A prospective observational study in two independent and different patient cohorts.

SETTING Two independent patient cohorts differing in surgical procedures were enrolled in two tertiary care hospitals between 2008 and 2016.

PATIENTS Consecutive patients of European origin undergoing elective surgery in two university hospitals. Clinical data were collected up to 24 h after surgery, and blood was drawn for genotyping. Of 2773 patients enrolled, 918 (Cohort A) and 1663 (Cohort B) with complete data sets were analysed.

MAIN OUTCOME MEASURE Patients were allocated to one of three groups (No PONV, Intermediate PONV or Severe PONV) depending on the frequency of vomiting, the severity of nausea and the need for antiemetics. Clinical variables and 13 genetic variants of seven candidate genes were evaluated for association with these three phenotypes. The cohorts were analysed separately by ordinal logistic regression analysis, treating PONV as a dependent ordinal three-stage variable. Odds ratios (ORs) with 95% confidence intervals were calculated.

RESULTS In Cohort A, the main predictors for PONV were female sex [OR (95% CI): 3.6 (2.7 to 4.8), P < 0.0001], nonsmoking status 1.8 (1.3 to 2.5), P < 0.001, the SS genotype (5-HTTLPR, rs4795541) of the promoter polymorphism in the serotonin transporter 1.5 (1.1 to 2.1), P = 0.019, and patient age 0.99 (0.98 to 0.99), P = 0.013. Analysis of Cohort B was consistent with these findings [5-HTTLPR: 1.8 (1.4 to 2.3), P < 0.00001]. Sex-specific regression models confirmed this 5-HTTLPR association in women and men.

CONCLUSION In two independent cohorts, in addition to the well known clinical factors, a polymorphism of 5-HTTLPR in the serotonin transporter was independently associated with PONV. A possible evaluation of this biomarker to improve risk prediction within the scope of precision medicine should be considered.

TRIAL REGISTRATION Clinicaltrials.gov identifier NCT03490175

From the Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, and Department of BioMedical Research, University of Bern, Switzerland (UMS, MS, TW, CL, LZ, FS), the Department of Anaesthesiology and Intensive Care Medicine, University of Bonn, Bonn, Germany (UMS), the Department of Visceral Surgery and Medicine, Inselspital Bern University Hospital, University of Bern, Bern, Switzerland (VBW), and the Research Division, Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany (MS)

Correspondence to Ulrike M. Stamer, MD, Department of Anaesthesiology and Pain Medicine, Inselspital, University of Bern, Freiburgstrasse, Bern 3010, Switzerland E-mail: ulrike.stamer@dbmr.unibe.ch

Published online 9 May 2019

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© 2019 European Society of Anaesthesiology