title: Association of μ-opioid receptor gene (OPRM1) haplotypes with postoperative nausea and vomiting.
abstract: Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the μ-opioid receptor gene (OPRM1) might be associated with individual differences in opioid sensitivity, as well as with the incidence and severity of postoperative nausea and vomiting (PONV). The goal of the present study was to determine, in a cohort of Japanese surgical patients, genotypes and haplotypes of several SNPs in the OPRM1 gene, and their association with PONV during the early (first 24 h) postoperative period. We examined the incidence and severity of PONV, during the first 24 h after surgery, in 85 Japanese patients receiving intravenous patient-controlled analgesia fentanyl analgesia for postoperative pain control. Eight tag SNPs of the OPRM1 gene (rs1799971, A/G; rs510769, G/A; rs4870266, G/A; rs3798683, G/A; rs1323042, A/C; rs609623, C/T; rs9397685, A/G; and rs644261, C/G) were selected based on their minor allele frequency (>10%) and linkage disequilibrium strength (<80%), and genotyped for haplotype analysis and determination of associations with PONV. Only one out of eight investigated SNPs, rs9397685, in the intronic part of the OPRM1 gene was associated with differences in the occurrence and severity of PONV. We also found four common haplotypes with a frequency of >10% in the investigated patients, including GGGAACAC (33%), AGGGACAC (19%), GGGAACGC (12%), and AGAGACAC (10%). The severity of PONV in carriers of the GGGAACGC haplotype was significantly lower than in the carriers of the other haplotypes (P < 0.05). One intronic SNP, rs9397685, and haplotypes constructed from eight SNPs within the OPRM1 gene locus might be involved in the severity of PONV associated with general anesthesia and opioid administration. This novel finding, if validated and verified in larger and additional ethnic cohorts, might contribute to better knowledge of the contribution of the OPRM1 gene to PONV.
authors.affiliation: Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan, sugino@ruby.ocn.ne.jp.
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Sugino
authors.forename: Tomo
authors.initials: T
authors.lastname: Hayase
authors.forename: Misako
authors.initials: M
authors.lastname: Higuchi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Saito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Moriya
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kumeta
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kurosawa
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Namiki
authors.forename: Piotr K
authors.initials: PK
authors.lastname: Janicki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020250:Postoperative Nausea and Vomiting / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D064232:Visual Analog Scale; D055815:Young Adult
chemical_list: C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu