García-Martín Elena, Ramos María I, Cornejo-García José A, Galván Segismundo, Perkins James R, Rodríguez-Santos Laura, Alonso-Navarro Hortensia, Jiménez-Jiménez Félix J, Agúndez José A G
Department of Pharmacology, Universidad de Extremadura, Cáceres, Spain.
ARADyAL Network, Instituto de Salud Carlos III, Madrid, Spain.
Front Cell Neurosci. 2018 Jan 31;12:10. doi: 10.3389/fncel.2018.00010. eCollection 2018.
The Gamma-aminobutyric acid type A receptor (GABA-A receptor) is affected by ethanol concentrations equivalent to those reached during social drinking. At these concentrations, ethanol usually causes impairment in reaction and motor times in most, but not all, individuals. To study the effect of GABA-A receptor variability in motor and reaction times, and the effect of low ethanol doses. Two hundred and fifty healthy subjects received one single dose of 0.5 g/Kg ethanol . Reaction and motor times were determined before ethanol challenge (basal), and when participants reached peak ethanol concentrations. We analyzed all common missense polymorphisms described in the 19 genes coding for the GABA-A receptor subunits by using TaqMan probes. The rs4454083 T/C polymorphisms were related to motor times, with individuals carrying the C/C genotype having faster motor times, both, at basal and at peak ethanol concentrations. The rs2229940 T/T genotype was associated to faster reaction times and with lower ethanol effects, determined as the difference between basal reaction time and reaction time at peak concentrations. All these associations remained significant after correction for multiple comparisons. No significant associations were observed for the common missense SNPs rs12910925, rs211035, rs1139916, rs1063310, rs3810651, rs12200969 or rs1186902, rs282129, and rs832032. This study provides novel information supporting a role of missense GABA-A receptor polymorphisms in reaction time, motor time and effects of low ethanol doses .
γ-氨基丁酸A型受体（GABA-A受体）会受到与社交饮酒时达到的浓度相当的乙醇浓度的影响。在这些浓度下，乙醇通常会使大多数（但不是所有）个体的反应和运动时间受损。为了研究GABA-A受体变异性对运动和反应时间的影响，以及低剂量乙醇的影响。250名健康受试者接受了0.5 g/Kg乙醇的单次剂量。在乙醇激发前（基础状态）以及参与者达到乙醇峰值浓度时测定反应和运动时间。我们使用TaqMan探针分析了编码GABA-A受体亚基的19个基因中描述的所有常见错义多态性。rs4454083 T/C多态性与运动时间相关，携带C/C基因型的个体在基础状态和乙醇峰值浓度时的运动时间都更快。rs2229940 T/T基因型与更快的反应时间以及较低的乙醇效应相关，乙醇效应定义为基础反应时间与峰值浓度时反应时间的差值。在进行多重比较校正后，所有这些关联仍然显著。对于常见错义单核苷酸多态性rs12910925、rs211035、rs1139916、rs1063310、rs3810651、rs12200969或rs1186902、rs282129和rs832032，未观察到显著关联。这项研究提供了新的信息，支持错义GABA-A受体多态性在反应时间、运动时间和低剂量乙醇效应中的作用。
