title: Positive association of dopamine D2 receptor polymorphism with bipolar affective disorder in a European Multicenter Association Study of affective disorders.
abstract: 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.
authors.affiliation: Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Brussels, Belgium. imassat@ulb.ac.be
authors.forename: Isabelle
authors.initials: I
authors.lastname: Massat
authors.forename: Daniel
authors.initials: D
authors.lastname: Souery
authors.forename: Jurgen
authors.initials: J
authors.lastname: Del-Favero
authors.forename: Sofie
authors.initials: S
authors.lastname: Van Gestel
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
authors.forename: Fabio
authors.initials: F
authors.lastname: Macciardi
authors.forename: Enrico
authors.initials: E
authors.lastname: Smeraldi
authors.forename: Radka
authors.initials: R
authors.lastname: Kaneva
authors.forename: Rolf
authors.initials: R
authors.lastname: Adolfsson
authors.forename: Peter O
authors.initials: PO
authors.lastname: Nylander
authors.forename: Douglas
authors.initials: D
authors.lastname: Blackwood
authors.forename: Walter
authors.initials: W
authors.lastname: Muir
authors.forename: George N
authors.initials: GN
authors.lastname: Papadimitriou
authors.forename: Dimitris
authors.initials: D
authors.lastname: Dikeos
authors.forename: Lilijana
authors.initials: L
authors.lastname: Oruc
authors.forename: Ronnen H
authors.initials: RH
authors.lastname: Segman
authors.forename: Sladjana
authors.initials: S
authors.lastname: Ivezic
authors.forename: Harold
authors.initials: H
authors.lastname: Aschauer
authors.forename: Manfred
authors.initials: M
authors.lastname: Ackenheil
authors.forename: S
authors.initials: S
authors.lastname: Fuchshuber
authors.forename: Henrik
authors.initials: H
authors.lastname: Dam
authors.forename: Miro
authors.initials: M
authors.lastname: Jakovljevic
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Christiane
authors.initials: C
authors.lastname: Hilger
authors.forename: François
authors.initials: F
authors.lastname: Hentges
authors.forename: Luc
authors.initials: L
authors.lastname: Staner
authors.forename: Vihra
authors.initials: V
authors.lastname: Milanova
authors.forename: Elena
authors.initials: E
authors.lastname: Jazin
authors.forename: Bernard
authors.initials: B
authors.lastname: Lerer
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Julien
authors.initials: J
authors.lastname: Mendlewicz
mesh_terms: 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
chemical_list: C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D004247:DNA