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Pharmacogenomics J. 2018 Jul;18(4):565-577. doi: 10.1038/s41397-018-0023-7. Epub 2018 May 3.

Gamma-aminobutyric acid (GABA) receptors genes polymorphisms and risk for restless legs syndrome.

Author information

1
Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey (Madrid), Madrid, Spain. fjavier.jimenez@salud.madrid.org.
2
Department of Medicine-Neurology, Hospital "Príncipe de Asturias", Universidad de Alcalá, Alcalá de Henares (Madrid), Madrid, Spain. fjavier.jimenez@salud.madrid.org.
3
University Institute of Molecular Pathology Biomarkers, UNEx. ARADyAL Instituto de Salud Carlos III, Cáceres, Spain.
4
Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey (Madrid), Madrid, Spain.
5
Department of Medicine-Neurology, Hospital "Príncipe de Asturias", Universidad de Alcalá, Alcalá de Henares (Madrid), Madrid, Spain.
6
Section of Neurology, Hospital Virgen del Puerto, Plasencia (Cáceres), Spain.
7
Section of Neurology, Hospital La Mancha-Centro, Alcázar de San Juan (Ciudad Real), Ciudad Real, Spain.
8
Unit of Neurology, Hospital Recoletas, Zamora, Spain.
9
Section of Neurology, Hospital Universitario de Burgos, Burgos, Spain.
10
Fundació per la Recerca Biomèdica i Social Mútua de Terrassa, Terrassa, Barcelona, Spain.
11
Memory and Movement Disorders Units, Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain.
12
CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.
13
Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, Universidad de Navarra, Pamplona, Spain.

Abstract

The possible role of gammaaminobutyric acid (GABA) in the pathophysiology of restless legs syndrome (RLS) is suggested by the symptomatic improvement achieved with GABAergic drugs. Thalamic GABA levels have shown positive correlation with periodic limb movements indices and with RLS severity. We tried to investigate the possible association between the most common single nucleotide polymorphisms (SNPs) in the GABA receptors (GABR) genes rho1, 2, and 3 (GABRR1, GABRR2, GABRR3), alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) with the risk of developing RLS. We studied the genotype and allelic variant frequencies of the most common SNPs in the GABRR1(rs12200969, rs1186902), GABRR2(rs282129), GABRR3(rs832032), GABRA4(rs2229940), GABRE(rs1139916), and GABRQ(rs3810651) genes in 205 RLS patients and 230 age- and gender-matched healthy controls using specific TaqMan assays. The frequencies of the GABRR3 rs832032TT genotype and the allelic variant GABRR3 rs832032T were significantly higher in RLS patients than in controls (odds ratio [95% confidence intervals] 7.08[1.48-46.44] and 1.66[1.16-2.37], respectively), although only the higher frequency of the rs832032T allele remained as significant after multiple comparison analysis, both in the whole series and in the female gender. The frequencies of the other genotypes of allelic variants did not differ significantly between RLS patients and controls. RLS patients carrying the GABRA4 rs2229940TT genotype showed a significantly younger age at onset of RLS symptoms than those with the other two genotypes. These results suggest association between GABRR3rs832032 polymorphism and the risk for RLS, and a modifier effect of GABRA4 rs2229940 on the age of onset of RLS.

PMID:
29720720
DOI:
10.1038/s41397-018-0023-7
[Indexed for MEDLINE]

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