Περίληψη:
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 (
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. (C) 2002 Wiley-Liss, Inc.
Συγγραφείς:
Massat, I
Souery, D
Del-Favero, J
Van Gestel, S and
Serretti, A
Macciardi, F
Smeraldi, E
Kaneva, R and
Adolfsson, R
Nylander, PO
Blackwood, D
Muir, W and
Papadimitriou, GN
Dikeos, D
Oruc, L
Segman, RH
Ivezic, S
and Aschauer, H
Ackenheil, M
Fuchshuber, S
Dam, H and
Jakovljevic, M
Peltonen, L
Hilger, C
Hentges, F
Staner,
L
Milanova, V
Jazin, E
Lerer, B
Van Broeckhoven, C and
Mendlewicz, J