Massat I, Souery D, Del-Favero J, Oruc L, Noethen M M, Blackwood D, Thomson M, Muir W, Papadimitriou G N, Dikeos D G, Kaneva R, Serretti A, Lilli R, Smeraldi E, Jakovljevic M, Folnegovic V, Rietschel M, Milanova V, Valente F, Van Broeckhoven C, Mendlewicz J
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Belgium.
Mol Psychiatry. 2002;7(2):201-7. doi: 10.1038/sj.mp.4000953.
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.
来自临床前和药理学研究中关于γ-氨基丁酸（GABA）作用的现有数据支持这样一种假说，即脑内GABA能系统活性功能障碍导致了双相情感障碍（BPAD）的易感性。此外，α3亚基GABA受体GABRA3基因定位于Xq28，这是某些形式双相情感障碍的一个感兴趣区域，提示GABRA3可能是BPAD的一个候选基因。在本研究中，我们在一个按性别和种族地理来源匹配的欧洲多中心病例对照样本中，检测了GABRA3二核苷酸多态性的遗传作用。比较了185例BPAD患者和370例对照的等位基因和基因型（女性）频率。与对照组相比，BPAD女性中基因型1-1显著增加（P = 0.0004）。此外，当考虑等位基因1的隐性（基因型为1-1的女性和携带等位基因1的男性）时，结果更显著（P = 0.00002）。我们的研究结果提示，GABRA3多态性可能赋予BPAD遗传易感性，或与参与BPAD遗传病因的另一个基因存在连锁不平衡。
