Genetic contribution to PONV risk

Abstract

Background: Clinical risk factors for postoperative nausea and vomiting (PONV) are usually stratified using the Apfel Score. While a genetic predisposition has recently been demonstrated with the muscarinic acetylcholine receptor (CHRM3) rs2165870 single nucleotide polymorphism (SNP), we investigated whether (1) other SNPs contribute to PONV risk and (2) a genetic risk score might summarise genetic PONV risk.

Methods: We retrospectively analysed data from a study with 472 patients undergoing elective surgery. We investigated the SNPs rs3218315 (IL2RB), rs349358 (KCNB2), rs703363 (intergenic variant), rs1800497 (DRD2), rs1799971 (OPRM1), and rs1176713 (HTR3A). A genetic risk score was established and association with PONV investigated.

Results: Early PONV occurred in 37%. There was a significant association of the KCNB2 rs349358 SNP with nausea (P = 0.021), retching (P = 0.001), and PONV (P = 0.006). The rs349358 genotype distribution was TT in 310 and TC/CC in 155 patients. The KCNB2 SNP was associated with an Odds Ratio (OR) of 1.6 for CT/CC vs. TT (95% CI 1-2.5; P = 0.031) to develop PONV and this was independent from the Apfel Score, and the CHRM3 rs2165870 SNP. A genetic risk score based on the CHRM3 rs2165870 and the KCNB2 rs349358 SNP was created and this genetic score (OR per genetic risk score point: 1.6 (1.3-2.1), P < 0.0001) was independent from the Apfel Score (OR per Apfel score point: 1.6 (1.3-1.9), P < 0.0001) associated with PONV.

Conclusion: The KCNB2 rs349358 SNP is also an independent PONV predictor and a genetic risk score has a similar impact on PONV susceptibility compared to the Apfel Score.

Keywords: Apfel score; Genetic predisposition; KCNB2; PONV; rs2165870; rs349358.