Massat Isabelle, Souery Daniel, Del-Favero Jurgen, Van Gestel Sofie, Serretti Alessandro, Macciardi Fabio, Smeraldi Enrico, Kaneva Radka, Adolfsson Rolf, Nylander Peter O, Blackwood Douglas, Muir Walter, Papadimitriou George N, Dikeos Dimitris, Oruc Lilijana, Segman Ronnen H, Ivezic Sladjana, Aschauer Harold, Ackenheil Manfred, Fuchshuber S, Dam Henrik, Jakovljevic Miro, Peltonen Leena, Hilger Christiane, Hentges François, Staner Luc, Milanova Vihra, Jazin Elena, Lerer Bernard, Van Broeckhoven Christine, Mendlewicz Julien
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Brussels, Belgium.
Am J Med Genet. 2002 Mar 8;114(2):177-85.
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.
传统遗传学和分子遗传学研究均支持情感障碍（AD）病因中存在遗传因素的有力证据，情感障碍包括双相情感障碍（BPAD）和单相情感障碍（UPAD）。大多数观点支持复杂遗传假说，表明遗传模式可能并非孟德尔式，而很可能是寡基因（或多基因）的，且基因的作用可能是中等或较弱的。本欧洲多中心研究（13个中心）的目的是采用病例对照关联设计，检验两个候选多巴胺能标记物DRD2和DRD3在BPAD和UPAD中的潜在作用。对以下样本进行了DRD2分析：358例BPAD患者/358例对照（C）以及133例UPAD患者/133例对照，对DRD3的分析样本为：325例BPAD患者/325例对照以及136例UPAD患者/136例对照。患者和对照在性别、年龄（±5岁）和地理来源方面进行了个体匹配。BPAD与DRD2之间出现显著关联的证据，与对照相比，BPAD病例中基因型5-5（P=0.004）和等位基因5（P=0.002）的比例过高。在UPAD中未发现DRD2存在关联，在BPAD或UPAD中均未发现DRD3存在关联。我们的结果表明，DRD2微卫星可能与附近一个参与BPAD易感性的基因变异处于连锁不平衡状态。我们的大型欧洲样本使得能够重复之前在其他研究人群中报道的一些阳性发现。
