Association between GABA(A) receptor subunit gene cluster and zolpidem-induced complex sleep behaviors in Han Chinese

Abstract

Study objectives: To investigate and elucidate the role of GABA(A) receptor subunits, specifically the 2 genetic markers at the GABA(A) α1 and GABA(A) α6 receptors, in zolpidem-induced complex sleep behaviors (CSBs).

Design: Genetic association study.

Setting: Kaohsiung Medical University-affiliated hospitals, Kaohsiung, Taiwan.

Patients: 30 zolpidem-induced CSB subjects and 37 controls.

Interventions: N/A.

Measurements and results: The χ(2) test demonstrated an association between the A15G variant at the GABA(A) α1 receptor subunit gene and zolpidem-induced CSBs (P = 0.007). The adjusted odds ratio of the GABA(A) α1 receptor subunit genotype for the risk of zolpidem-induced CSBs was approximately 10 (OR = 9.99, 95% CI = 1.82, 74.87; P = 0.013).

Conclusions: The finding reveals that the A15G variant at the GABA(A) α1 receptor subunit gene confers a high risk of zolpidem-induced CSBs and may be considered in clinical services.

Figure 1

3% agarose gel electrophoresis of the artificial AvaII RFLP for the A→G point substitution in the last intron of the GABA_A α1 receptor subunit gene. The 165-bp PCR product was then digested with AVA II restriction enzyme, which can cut at both G↓GTCC and G↓GACC. If there was a G at nucleotide position 15 of the least intron, then the 165-bp product would digest with AVA II into two fragments of 141 and 24 bp. If A was present at this position, then the AVA II restriction site would not be present and the PCR fragment would not digest.

Figure 2

2% agarose gel electrophoresis of the AlwNI RFLP for the T→C point substitution at nucleotide 1519 in the non-coding region of the GABA_A α6 receptor subunit gene. The 423-bp PCR product was digested with AlwNI restriction enzyme, which can cut at GAG↓NNN↓CTG. If there was a T at nucleotide position 1519, then the 423-bp product would digest with AlwNI into two fragments of 257 and 166 bp. If C was present at this position, then the AlwNI restriction site would not be present and the PCR fragment would not digest.