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

Authors
Choi, Yoon JiLee, Shin YuongYang, Kyung-SookPark, Ji-YoungYoon, Seung ZhooYoon, Suk Min
Issue Date
10월-2015
Publisher
SAGE PUBLICATIONS LTD
Keywords
Benzodiazepine; gamma-aminobutyric acid A receptor; genetic; polymorphism
Citation
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, v.43, no.5, pp.686 - 698
Indexed
SCIE
SCOPUS
Journal Title
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
Volume
43
Number
5
Start Page
686
End Page
698
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/92243
DOI
10.1177/0300060515587580
ISSN
0300-0605
Abstract
Objective To evaluate whether polymorphisms in the gamma-aminobutyric acid A receptor 1 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 0.02mg/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.
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