Damberg M, Garpenstrand H, Hallman J, Oreland L
Department of Neuroscience, Unit of Pharmacology, Uppsala University, SE-751 24 Uppsala, Sweden.
Mol Psychiatry. 2001 Sep;6(5):503-10. doi: 10.1038/sj.mp.4000935.
Major changes in psychiatric phenotypes due to genetic factors are seldom the result of single gene polymorphisms, but more often the result of several genetic mechanisms. In this millennium article we discuss the notion that the expression of numerous candidate genes could be regulated by the same transcription factors, and that polymorphisms in transcription factor genes might explain some phenotypes. We describe recent results of studies on the biological marker thrombocyte monoamine oxidase (trbc MAO) and the transcription factor AP-2beta. Low levels of trbc MAO is associated with temperamental characteristics such as sensation seeking and impulsiveness, and the enzyme is genetically regulated by specific transcriptional mechanisms. Transcription factor AP-2beta is important for the development of midbrain structures and AP-2beta has several binding sites in the regulatory regions of genes encoding key proteins in the monoamine transmitter systems. We have recently shown AP-2beta to be linked to personality, binge-eating disorder, treatment with antidepressant drugs, and also to trbc MAO. Regardless of whether transcriptions factors, such as AP-2beta, regulate the expression of eg, the number of monoamine neurons or a variety of candidate genes within the monoamine systems, or both, we would like to emphasize the role of transcription factors, besides polymorphisms in monoaminergic candidate genes, when explaining inter-individual differences in temperament and psychiatric vulnerability.
由遗传因素导致的精神疾病表型的重大变化很少是单基因多态性的结果，而更常见的是几种遗传机制共同作用的结果。在这篇千禧年文章中，我们讨论了这样一种观点：众多候选基因的表达可能受相同转录因子的调控，并且转录因子基因中的多态性可能解释某些表型。我们描述了关于生物标志物血小板单胺氧化酶（trbc MAO）和转录因子AP - 2β的最新研究结果。trbc MAO水平低与诸如寻求刺激和冲动等气质特征相关联，并且该酶受特定转录机制的遗传调控。转录因子AP - 2β对中脑结构的发育很重要，并且AP - 2β在单胺递质系统中编码关键蛋白的基因的调控区域有多个结合位点。我们最近发现AP - 2β与人格、暴饮暴食症、抗抑郁药物治疗有关，还与trbc MAO有关。无论诸如AP - 2β这样的转录因子是否调控例如单胺能神经元数量或单胺系统内各种候选基因的表达，或者两者都调控，我们都想强调转录因子在解释个体间气质和精神易感性差异时的作用，这除了单胺能候选基因中的多态性之外。
