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Association of μ-opioid receptor gene (OPRM1) haplotypes with postoperative nausea and vomiting

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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.

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Acknowledgments

This study was supported by a Grant-in-Aid for Young Scientists (B) (No. 20791085, 2008–2010, to Shigekazu Sugino) from the Ministry of Education, Culture, Sports Science and Technology, Tokyo, Japan. Presented in part at the American Society of Anesthesiologists 2010 Annual Meeting, San Diego, California, October 16–20, 2010. The author (S.S.) thanks the staff of the Department of Anesthesiology, Sapporo Medical University School of Medicine, for providing valuable comments regarding the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Anesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan

    Shigekazu Sugino, Tomo Hayase, Yukihiro Kumeta & Akiyoshi Namiki

  2. Department of Anesthesia, Otaru Municipal Hospital, 2-1, Wakamatsu 1, Otaru, Hokkaido, 047-0017, Japan

    Shigekazu Sugino, Tomo Hayase, Misako Higuchi & Yukihiro Kumeta

  3. Department of Pharmacy, Hokkaido Pharmaceutical University School of Pharmacy, 7-1, Katsuraoka-cho, Otaru, Hokkaido, 047-0264, Japan

    Katsuhiko Saito, Hiroyuki Moriya & Nahoko Kurosawa

  4. Laboratory of Perioperative Genomics, Department of Anesthesiology, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033-0850, USA

    Shigekazu Sugino & Piotr K. Janicki

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  1. Shigekazu Sugino
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  2. Tomo Hayase
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  3. Misako Higuchi
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  4. Katsuhiko Saito
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  9. Piotr K. Janicki
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Correspondence to Shigekazu Sugino.

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Sugino, S., Hayase, T., Higuchi, M. et al. Association of μ-opioid receptor gene (OPRM1) haplotypes with postoperative nausea and vomiting. Exp Brain Res 232, 2627–2635 (2014). https://doi.org/10.1007/s00221-014-3987-9

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  • DOI: https://doi.org/10.1007/s00221-014-3987-9

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