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論文
- タイトル
- タイトル（英）
- γ-Aminobutyric acid type A receptor β1 subunit gene polymorphisms are associated with the sedative and amnesic effects of midazolam
- 参照URL
- https://researchmap.jp/daisuke_nishizawa/published_papers/48104751
- 著者
- 著者（英）
- Yoshihiko Kosaki,Daisuke Nishizawa,Junko Hasegawa,Kaori Yoshida,Kazutaka Ikeda,Tatsuya Ichinohe
- 担当区分
- 概要
- 概要（英）
- Abstract Midazolam is widely used for intravenous sedation. However, wide interindividual variability is seen in the sensitivity to midazolam. The association between genetic factors and interindividual differences in midazolam sensitivity remains unclear. The present study explored the association between common genetic variants and sedative and amnesic effects of midazolam. This prospective study included patients who were scheduled to undergo dental procedures under intravenous sedation. The sedative effect was evaluated using the Ramsay sedation scale 5 min after midazolam (0.05 mg/kg) administration. We employed two parallel approaches in this study: genome-wide approach and candidate gene approach. The γ-aminobutyric acid type A receptor subunit genes were selected as candidate genes. Multivariate linear regression analyses were performed to investigate the association between the Ramsay sedation scale and genetic variants. We also analyzed the association between the presence of anterograde amnesia and genetic variants using multivariate binominal logistic regression analyses. The analyses were adjusted for potential confounding factors. A total of 191 patients were included in the analyses. In the genome-wide association analyses, no significant association was found between the genetic variants and Ramsay scores. In the candidate gene analyses, the rs73247636 (dominant model: β = 0.72 [95% confidence interval, 0.34 to 1.10], P < 0.001) and rs56278524 (dominant model: β = 0.73 [0.37 to 1.10], P < 0.001) polymorphisms of the GABRB1 gene were significantly associated with Ramsay scores. Additionally, the rs73247636 (dominant model: odds ratio [OR] = 8.39 [2.36 to 29.85], P = 0.001) and rs56278524 (dominant model: OR = 15.26 [3.42 to 68.07], P < 0.001) polymorphisms were also significantly associated with the presence of anterograde amnesia. The rs73247636 and rs56278524 single-nucleotide polymorphisms of GABRB1 were associated with the sedative and amnesic effects of midazolam.
- 出版者・発行元
- 出版者・発行元（英）
- Springer Science and Business Media LLC
- 誌名
- 誌名（英）
- Molecular Brain
- 巻
- 17
- 号
- 1
- 開始ページ
- 終了ページ
- 出版年月
- 2024年9月27日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1186/s13041-024-01141-2
- 共同研究・競争的資金等の研究課題