Polymorphism rs4263535 in <i>GABRA1</i> intron 4 was related to deeper sedation by intravenous midazolam

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

doi:10.1177/0300060515587580

Cited by 14 publications

(9 citation statements)

References 35 publications

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“…Finally, a link between sleep-related behaviors and the GABAA receptor genes GABRA1 and GABRA2 (or Gabra1 and Gabra2) has been found in various human and animal studies [18][19][20][21]. However, we did not detect an association of GABRA1 and GABRA2 with sleep duration in the Taiwanese population.…”

Section: Discussioncontrasting

confidence: 77%

“…GABAA receptors are coded by GABAA receptor genes such as gamma-aminobutyric acid type A receptor subunit alpha1 (GABRA1). Studies have suggested a connection between GABAA receptor genes and sleeprelated behaviors [18][19][20][21]. For example, Tsai et al [19] indicated a significant association between zolpideminduced complex sleep behaviors and the A15G variant in the GABAA receptor gene GABRA1 in the Taiwanese population.…”

Section: Introductionmentioning

confidence: 99%

“…For example, Tsai et al [19] indicated a significant association between zolpideminduced complex sleep behaviors and the A15G variant in the GABAA receptor gene GABRA1 in the Taiwanese population. Choi et al [18] also reported that the rs4263535 single-nucleotide polymorphism (SNP) in the GABAA receptor gene GABRA1 contributes to sleep induction time during sedation induction using intravenous midazolam in the Korean population. In addition, Blednov et al [21] suggested that Gabra1 or Gabra2 knockout mice (i.e., with the deletion or loss of the Gabra1 or Gabra2 gene) exhibited significantly reduced sleep time, which was induced by GABAA agonists.…”

Section: Introductionmentioning

confidence: 99%

“…Based on the aforementioned considerations, we conducted the first genetic association study on the relationships between GABAA receptor genes such as GABRA1, GABRA2, GABRB3, GABRA5, and GABRG3 and sleep duration, sleep quality, and sleep timing in Taiwanese subjects from the Taiwan Biobank. Although there are other GABAA receptor genes, this pilot study focused on these five genes (i.e., GABRA1, GABRA2, GABRB3, GABRA5, and GABRG3) due to more studies on these genes based on previous literature [18][19][20][21][22][23][24][25][26][27][28]. Moreover, we performed interaction analyses on sleep duration as per previously described methods [31][32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

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An association study in the Taiwan Biobank elicits the GABAA receptor genes GABRB3, GABRA5, and GABRG3 as candidate loci for sleep duration in the Taiwanese population

et al. 2021

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Background Gamma-aminobutyric acid type A (GABAA) receptors mainly mediate the effects of gamma-aminobutyric acid, which is the primary inhibitory neurotransmitter in the central nervous system. Abundant evidence suggests that GABAA receptors play a key role in sleep-regulating processes. No genetic association study has explored the relationships between GABAA receptor genes and sleep duration, sleep quality, and sleep timing in humans. Methods We determined the association between single-nucleotide polymorphisms (SNPs) in the GABAA receptor genes GABRA1, GABRA2, GABRB3, GABRA5, and GABRG3 and sleep duration, sleep quality, and sleep timing in the Taiwan Biobank with a sample of 10,127 Taiwanese subjects. There were 10,142 subjects in the original study cohort. We excluded 15 subjects with a medication history of sedative-hypnotics. Results Our data revealed an association of the GABRB3-GABRA5-GABRG3 gene cluster with sleep duration, which has not been previously identified: rs79333046 (beta = − 0.07; P = 1.21 × 10–3) in GABRB3, rs189790076 (beta = 0.92; P = 1.04 × 10–3) in GABRA5, and rs147619342 (beta = − 0.72; P = 3.97 × 10–3) in GABRG3. The association between rs189790076 in GABRA5 and sleep duration remained significant after Bonferroni correction. A variant (rs12438141) in GABRB3 was also found to act as a potential expression quantitative trait locus. Additionally, we discovered interactions between variants in the GABRB3-GABRA5-GABRG3 gene cluster and lifestyle factors, such as tea and coffee consumption, smoking, and physical activity, that influenced sleep duration, although some interactions became nonsignificant after Bonferroni correction. We also found interactions among GABRB3, GABRA5, and GABRG3 that affected sleep duration. Furthermore, we identified an association of rs7165524 (beta = − 0.06; P = 2.20 × 10–3) in GABRA5 with sleep quality and an association of rs79465949 (beta = − 0.12; P = 3.95 × 10–3) in GABRB3 with sleep timing, although these associations became nonsignificant after Bonferroni correction. However, we detected no evidence of an association of individual SNPs in GABRA1 and GABRA2. Conclusions Our results indicate that rs189790076 in GABRA5 and gene–gene interactions among GABRB3, GABRA5, and GABRG3 may contribute to sleep duration in the Taiwanese population.

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Section: Discussioncontrasting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An association study in the Taiwan Biobank elicits the GABAA receptor genes GABRB3, GABRA5, and GABRG3 as candidate loci for sleep duration in the Taiwanese population

et al. 2021

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“…Benzodiazepines, acting through GABA A receptors, are used for anxiolysis and sedation in the perioperative period. A polymorphism in GABRA1 gene (encoding GABA A receptor) has been shown to influence benzodiazepine sensitivity [110]. Benzodiazepines are metabolized by CYP450 enzymes; midazolam is hydrolyzed by CYP3A4 and CYP3A5 enzymes, while diazepam is a CYP2C19 substrate.…”

Section: Sedative Hypnotics and Volatile Agentsmentioning

confidence: 99%

Personalized Pediatric Anesthesia and Pain Management: Problem-Based Review

et al. 2019

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Pharmacogenetics, the genetic influence on the interpersonal variability in drug response, has enabled tailored pharmacotherapy and emerging ‘personalized medicine.’ Although oncology spearheaded the clinical implementation of personalized medicine, other specialties are rapidly catching up. In anesthesia, classical examples of genetically mediated idiosyncratic reactions have been long known (e.g., malignant hyperthermia and prolonged apnea after succinylcholine). The last two decades have witnessed an expanding body of pharmacogenetic evidence in anesthesia. This review highlights some of the prominent pharmacogenetic associations studied in anesthesia and pain management, with special focus on pediatric anesthesia.

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