Excess of allele1 for alpha3 subunit GABA receptor gene (GABRA3) in bipolar patients: a multicentric association study.
The available data from preclinical and pharmacological studies on the role of gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in brain GABAergic system activity contributes to the vulnerability to bipolar affective disorders (BPAD). Moreover, the localization of the alpha3 subunit GABA receptor GABRA3 gene on the Xq28, a region of interest in certain forms of bipolar illness, suggests that GABRA3 may be a candidate gene in BPAD. In the present study, we tested the genetic contribution of the GABRA3 dinucleotide polymorphism in a European multicentric case-control sample, matched for sex and ethnogeographical origin. Allele and genotype (in females) frequencies were compared in 185 BPAD patients and 370 controls. A significant increase of genotype 1-1 was observed in BPAD females compared to controls (P=0.0004). Furthermore, when considering recessivity of allele 1 (females with genotype 1-1 and males carrying allele 1), results were even more significant (P= 0.00002). Our findings suggest that the GABRA3 polymorphism may confer susceptibility to or may be in linkage disequilibrium with another gene involved in the genetic etiology of BPAD.
Massat
I
I
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Belgium. imassat@ulb.ac.be
Souery
D
D
Del-Favero
J
J
Oruc
L
L
Noethen
M M
MM
Blackwood
D
D
Thomson
M
M
Muir
W
W
Papadimitriou
G N
GN
Dikeos
D G
DG
Kaneva
R
R
Serretti
A
A
Lilli
R
R
Smeraldi
E
E
Jakovljevic
M
M
Folnegovic
V
V
Rietschel
M
M
Milanova
V
V
Valente
F
F
Van Broeckhoven
C
C
Mendlewicz
J
J
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D018079:Receptors, GABA / Q000235:genetics*; D014960:X Chromosome
D018079:Receptors, GABA