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.