Long non-coding RNA MIR4300HG polymorphisms are associated with postoperative nausea and vomiting: a genome-wide association study

Abstract

Background: Genetic factors such as single nucleotide polymorphisms (SNPs) play a key role in the development of postoperative nausea and vomiting (PONV). However, previous findings are not widely applicable to different populations because of population-specific genetic variation. We developed a Japanese-specific DNA microarray for high-throughput genotyping. The aim of the current study is to identify causal SNPs associated with PONV on a genome-wide scale using this microarray in a sample of Japanese surgical patients. Methods: Genomic DNA was obtained from 256 surgical patients. We first determined associations between 659,636 SNPs and the incidence of PONV 24hrs after surgery in a limited sample of 24 female patients using the microarray. After imputation of genotypes at 24,330,529 SNPs, 78 SNPs were found to be associated with the incidence of PONV. We chose 4 of the 78 SNPs to focus on by in silico functional annotation. Finally, we genotyped these 4 candidate SNPs in 255 patients using real-time PCR to verify association with the incidence of PONV. Results: The T > C variant of rs11232965 in the long non-coding RNA MIR4300HG was significantly associated with reduced incidence of PONV among genotypes and between alleles (p = 0.01 and 0.007). Conclusions: We identified a novel causal SNP (rs11232965) in the long non-coding RNA MIR4300HG that is associated with PONV. The rs11232965-SNP variant (T > C) is protective against the incidence of PONV. Trial registration: This study was registered at the UMIN Clinical Trials Registry (Identifier: UMIN000022903, date of registration: June 27th, 2016, retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000026392).