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Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with Reaction Time, Motor Time, and Ethanol Effects in Vivo

Background: 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. Objectives: To...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797743/
https://www.ncbi.nlm.nih.gov/pubmed/29445327
http://dx.doi.org/10.3389/fncel.2018.00010
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author 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.
author_facet 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.
author_sort García-Martín, Elena
collection PubMed
description Background: 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. Objectives: To study the effect of GABA-A receptor variability in motor and reaction times, and the effect of low ethanol doses. Methods: Two hundred and fifty healthy subjects received one single dose of 0.5 g/Kg ethanol per os. 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. Results: The GABRA6 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 GABRA4 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 GABRB3 rs12910925, GABRG2 rs211035, GABRE rs1139916, GABRP rs1063310, GABRQ rs3810651, GABRR1 rs12200969 or rs1186902, GABRR2 rs282129, and GABRR3 rs832032. Conclusions: 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 in vivo.
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spelling pubmed-57977432018-02-14 Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with Reaction Time, Motor Time, and Ethanol Effects in Vivo 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. Front Cell Neurosci Neuroscience Background: 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. Objectives: To study the effect of GABA-A receptor variability in motor and reaction times, and the effect of low ethanol doses. Methods: Two hundred and fifty healthy subjects received one single dose of 0.5 g/Kg ethanol per os. 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. Results: The GABRA6 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 GABRA4 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 GABRB3 rs12910925, GABRG2 rs211035, GABRE rs1139916, GABRP rs1063310, GABRQ rs3810651, GABRR1 rs12200969 or rs1186902, GABRR2 rs282129, and GABRR3 rs832032. Conclusions: 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 in vivo. Frontiers Media S.A. 2018-01-31 /pmc/articles/PMC5797743/ /pubmed/29445327 http://dx.doi.org/10.3389/fncel.2018.00010 Text en Copyright © 2018 García-Martín, Ramos, Cornejo-García, Galván, Perkins, Rodríguez-Santos, Alonso-Navarro, Jiménez-Jiménez and Agúndez. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
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.
Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with Reaction Time, Motor Time, and Ethanol Effects in Vivo
title Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with Reaction Time, Motor Time, and Ethanol Effects in Vivo
title_full Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with Reaction Time, Motor Time, and Ethanol Effects in Vivo
title_fullStr Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with Reaction Time, Motor Time, and Ethanol Effects in Vivo
title_full_unstemmed Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with Reaction Time, Motor Time, and Ethanol Effects in Vivo
title_short Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with Reaction Time, Motor Time, and Ethanol Effects in Vivo
title_sort missense gamma-aminobutyric acid receptor polymorphisms are associated with reaction time, motor time, and ethanol effects in vivo
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797743/
https://www.ncbi.nlm.nih.gov/pubmed/29445327
http://dx.doi.org/10.3389/fncel.2018.00010
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