Positive association of dopamine D2 receptor polymorphism with bipolar affective disorder in a European Multicenter Association Study of affective disorders.
Convincing evidence for a genetic component in the etiology of affective disorders (AD), including bipolar affective disorder (BPAD) and unipolar affective disorder (UPAD), is supported by traditional and molecular genetic studies. Most arguments lead to the complex inheritance hypothesis, suggesting that the mode of inheritance is probably not Mendelian but most likely oligogenic (or polygenic) and that the contribution of genes could be moderate or weak. The purpose of the present European multicenter study (13 centers) was to test the potential role in BPAD and UPAD of two candidate dopaminergic markers, DRD2 and DRD3, using a case-control association design. The following samples were analyzed for DRD2: 358 BPAD/358 control (C) and 133 UPAD/ 133 C subjects, and for DRD3: 325 BPAD/ 325 C and 136 UPAD/136 C subjects. Patients and controls were individually matched for sex, age ( plus minus five years) and geographical origin. Evidence for significant association between BPAD and DRD2 emerged, with an over-representation of genotype 5-5 (P=0.004) and allele 5 (P=0.002) in BPAD cases compared to controls. No association was found for DRD2 in UPAD, and for DRD3 neither in BPAD or UPAD. Our results suggest that the DRD2 microsatellite may be in linkage disequilibrium with a nearby genetic variant involved in the susceptibility to BPAD. Our large European sample allowed for replicating of some previous reported positive findings obtained in other study populations.
Massat
Isabelle
I
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Brussels, Belgium. imassat@ulb.ac.be
Souery
Daniel
D
Del-Favero
Jurgen
J
Van Gestel
Sofie
S
Serretti
Alessandro
A
Macciardi
Fabio
F
Smeraldi
Enrico
E
Kaneva
Radka
R
Adolfsson
Rolf
R
Nylander
Peter O
PO
Blackwood
Douglas
D
Muir
Walter
W
Papadimitriou
George N
GN
Dikeos
Dimitris
D
Oruc
Lilijana
L
Segman
Ronnen H
RH
Ivezic
Sladjana
S
Aschauer
Harold
H
Ackenheil
Manfred
M
Fuchshuber
S
S
Dam
Henrik
H
Jakovljevic
Miro
M
Peltonen
Leena
L
Hilger
Christiane
C
Hentges
François
F
Staner
Luc
L
Milanova
Vihra
V
Jazin
Elena
E
Lerer
Bernard
B
Van Broeckhoven
Christine
C
Mendlewicz
Julien
J
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005060:Europe; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3
C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D004247:DNA