Department of Psychiatry, The University of Iowa, Iowa City, IA, USA.
Biol Psychol. 2011 Jul;87(3):366-71. doi: 10.1016/j.biopsycho.2011.04.007. Epub 2011 May 7.
Monoamine Oxidase A (MAOA) is a critical enzyme in the catabolism of monoaminergic neurotransmitters. MAOA transcriptional activity is thought to be regulated by a well characterized 30 base pair (bp) variable nucleotide repeat (VNTR) that lies approximately ∼1000 bp upstream of the transcriptional start site (TSS). However, clinical associations between this VNTR genotype and behavioral states have been inconsistent. Herein, we describe a second, 10 bp VNTR that lies ∼1500 bp upstream of the TSS. We provide in vitro and in silico evidence that this new VNTR region may be more influential in regulating MAOA transcription than the more proximal VNTR and that methylation of this CpG-rich VNTR is genotype dependent in females. Finally, we demonstrate that genotype at this new VNTR interacts significantly with history of child abuse to predict antisocial personality disorder (ASPD) in women and accounts for variance in addition to that explained by the prior VNTR.
单胺氧化酶 A（MAOA）是单胺能神经递质代谢中的关键酶。MAOA 的转录活性被认为受一个特征明确的 30 个碱基对（bp）可变核苷酸重复（VNTR）调控，该重复位于转录起始位点（TSS）上游约 1000bp。然而，这种 VNTR 基因型与行为状态之间的临床关联一直不一致。在此，我们描述了一个位于 TSS 上游约 1500bp 的第二个 10bp VNTR。我们提供了体外和计算机模拟证据，表明这个新的 VNTR 区域可能比更靠近 TSS 的 VNTR 更能影响 MAOA 的转录，并且该富含 CpG 的 VNTR 的甲基化在女性中是依赖基因型的。最后，我们证明该新 VNTR 的基因型与儿童虐待史显著相互作用，可预测女性反社会人格障碍（ASPD），并能解释除先前 VNTR 之外的变异性。
