Polymorphism rs4263535 in GABRA1 intron 4 was related to deeper sedation by intravenous midazolam

Yoon Ji Choi; Shin Yuong Lee; Kyung Sook Yang; Ji Young Park; Seung Zhoo Yoon; Suk Min Yoon

doi:10.1177/0300060515587580

Polymorphism rs4263535 in GABRA1 intron 4 was related to deeper sedation by intravenous midazolam

Yoon Ji Choi, Shin Yuong Lee, Kyung Sook Yang, Ji Young Park, Seung Zhoo Yoon, Suk Min Yoon

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

Objective To evaluate whether polymorphisms in the gamma-aminobutyric acid A receptor α1 subunit (GABRA1) gene influence sleep induction time, bispectral index score (BIS) during sleep induction and the total dose of midazolam required to reach a Ramsay Sedation Assessment Scale (RSAS) score of 4. Methods Patients scheduled for elective orthopaedic surgery were enrolled. All patients received initial doses of 0.02 mg/kg intravenous midazolam. If the RSAS score did not reach 4, an additional 1-mg dose of midazolam was administered. Results were compared among groups of patients with five single-nucleotide polymorphisms (SNPs) in GABRA1: rs4263535, rs980791, rs6556562, rs998754 and rs2279020. Results A total of 104 patients were evaluated. Polymorphism rs4263535 was associated with the lowest BIS during sedation induction. Multinomial logistic regression analysis demonstrated that polymorphism rs4263535 was significantly associated with the total dose of midazolam required for sedation induction. Conclusions Polymorphism rs4263535 in GABRA1 intron 4 was associated with deeper sedation by intravenous midazolam. Patients with the A/A rs4263535 genotype required a smaller dose of midazolam.

Original language	English
Pages (from-to)	686-698
Number of pages	13
Journal	Journal of International Medical Research
Volume	43
Issue number	5
DOIs	https://doi.org/10.1177/0300060515587580
Publication status	Published - 2015 Oct 22
Externally published	Yes

Keywords

Benzodiazepine
gamma-aminobutyric acid A receptor
genetic
polymorphism

ASJC Scopus subject areas

Biochemistry
Biochemistry, medical
Cell Biology

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10.1177/0300060515587580

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@article{a40de88cd00d4ce48a1b83bfc178f53b,

title = "Polymorphism rs4263535 in GABRA1 intron 4 was related to deeper sedation by intravenous midazolam",

abstract = "Objective To evaluate whether polymorphisms in the gamma-aminobutyric acid A receptor α1 subunit (GABRA1) gene influence sleep induction time, bispectral index score (BIS) during sleep induction and the total dose of midazolam required to reach a Ramsay Sedation Assessment Scale (RSAS) score of 4. Methods Patients scheduled for elective orthopaedic surgery were enrolled. All patients received initial doses of 0.02 mg/kg intravenous midazolam. If the RSAS score did not reach 4, an additional 1-mg dose of midazolam was administered. Results were compared among groups of patients with five single-nucleotide polymorphisms (SNPs) in GABRA1: rs4263535, rs980791, rs6556562, rs998754 and rs2279020. Results A total of 104 patients were evaluated. Polymorphism rs4263535 was associated with the lowest BIS during sedation induction. Multinomial logistic regression analysis demonstrated that polymorphism rs4263535 was significantly associated with the total dose of midazolam required for sedation induction. Conclusions Polymorphism rs4263535 in GABRA1 intron 4 was associated with deeper sedation by intravenous midazolam. Patients with the A/A rs4263535 genotype required a smaller dose of midazolam.",

keywords = "Benzodiazepine, gamma-aminobutyric acid A receptor, genetic, polymorphism",

author = "Choi, {Yoon Ji} and Lee, {Shin Yuong} and Yang, {Kyung Sook} and Park, {Ji Young} and Yoon, {Seung Zhoo} and Yoon, {Suk Min}",

note = "Funding Information: This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI13C2181). No funding other than personal was used in conducting the audit as well as writing the manuscript. Publisher Copyright: {\textcopyright} 2015, {\textcopyright} The Author(s) 2015.",

year = "2015",

month = oct,

day = "22",

doi = "10.1177/0300060515587580",

language = "English",

volume = "43",

pages = "686--698",

journal = "Journal of International Medical Research",

issn = "0300-0605",

publisher = "Field House Publishing LLP",

number = "5",

}

TY - JOUR

T1 - Polymorphism rs4263535 in GABRA1 intron 4 was related to deeper sedation by intravenous midazolam

AU - Choi, Yoon Ji

AU - Lee, Shin Yuong

AU - Yang, Kyung Sook

AU - Park, Ji Young

AU - Yoon, Seung Zhoo

AU - Yoon, Suk Min

N1 - Funding Information: This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI13C2181). No funding other than personal was used in conducting the audit as well as writing the manuscript. Publisher Copyright: © 2015, © The Author(s) 2015.

PY - 2015/10/22

Y1 - 2015/10/22

N2 - Objective To evaluate whether polymorphisms in the gamma-aminobutyric acid A receptor α1 subunit (GABRA1) gene influence sleep induction time, bispectral index score (BIS) during sleep induction and the total dose of midazolam required to reach a Ramsay Sedation Assessment Scale (RSAS) score of 4. Methods Patients scheduled for elective orthopaedic surgery were enrolled. All patients received initial doses of 0.02 mg/kg intravenous midazolam. If the RSAS score did not reach 4, an additional 1-mg dose of midazolam was administered. Results were compared among groups of patients with five single-nucleotide polymorphisms (SNPs) in GABRA1: rs4263535, rs980791, rs6556562, rs998754 and rs2279020. Results A total of 104 patients were evaluated. Polymorphism rs4263535 was associated with the lowest BIS during sedation induction. Multinomial logistic regression analysis demonstrated that polymorphism rs4263535 was significantly associated with the total dose of midazolam required for sedation induction. Conclusions Polymorphism rs4263535 in GABRA1 intron 4 was associated with deeper sedation by intravenous midazolam. Patients with the A/A rs4263535 genotype required a smaller dose of midazolam.

AB - Objective To evaluate whether polymorphisms in the gamma-aminobutyric acid A receptor α1 subunit (GABRA1) gene influence sleep induction time, bispectral index score (BIS) during sleep induction and the total dose of midazolam required to reach a Ramsay Sedation Assessment Scale (RSAS) score of 4. Methods Patients scheduled for elective orthopaedic surgery were enrolled. All patients received initial doses of 0.02 mg/kg intravenous midazolam. If the RSAS score did not reach 4, an additional 1-mg dose of midazolam was administered. Results were compared among groups of patients with five single-nucleotide polymorphisms (SNPs) in GABRA1: rs4263535, rs980791, rs6556562, rs998754 and rs2279020. Results A total of 104 patients were evaluated. Polymorphism rs4263535 was associated with the lowest BIS during sedation induction. Multinomial logistic regression analysis demonstrated that polymorphism rs4263535 was significantly associated with the total dose of midazolam required for sedation induction. Conclusions Polymorphism rs4263535 in GABRA1 intron 4 was associated with deeper sedation by intravenous midazolam. Patients with the A/A rs4263535 genotype required a smaller dose of midazolam.

KW - Benzodiazepine

KW - gamma-aminobutyric acid A receptor

KW - genetic

KW - polymorphism

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U2 - 10.1177/0300060515587580

DO - 10.1177/0300060515587580

M3 - Article

C2 - 26249742

AN - SCOPUS:84942038575

SN - 0300-0605

VL - 43

SP - 686

EP - 698

JO - Journal of International Medical Research

JF - Journal of International Medical Research

IS - 5

ER -

Polymorphism rs4263535 in GABRA1 intron 4 was related to deeper sedation by intravenous midazolam

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