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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam-Si, Gyeonggi-do, Republic of Korea.
authors.forename: Yoon-Ji
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Sevrance UVA Surgery, Busan, Republic of Korea.
authors.forename: Shin Yuong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Biostatistics, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Kyung-Sook
authors.initials: KS
authors.lastname: Yang
authors.affiliation: Department of Clinical Pharmacology and Toxicology, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Anaesthesiology and Pain Medicine, College of Medicine, Korea University, Seoul, Republic of Korea yoonsz70@gmail.com.
authors.forename: Seung Zhoo
authors.initials: SZ
authors.lastname: Yoon
authors.affiliation: Department of Anaesthesiology and Pain Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Suk Min
authors.initials: SM
authors.lastname: Yoon
mesh_terms: D056805:Consciousness Monitors; D054810:Deep Sedation; D017558:Elective Surgical Procedures; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007438:Introns / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008874:Midazolam / Q000008:administration & dosage* / Q000494:pharmacology*; D019637:Orthopedic Procedures; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D018709:Statistics, Nonparametric
chemical_list: C546240:GABRA1 protein, human; D011963:Receptors, GABA-A; D008874:Midazolam
keywords: Benzodiazepine; gamma-aminobutyric acid A receptor; genetic; polymorphism