Philibert Robert A, Gunter Tracy D, Beach Steven R H, Brody Gene H, Madan Anup
Department of Psychiatry, The University of Iowa, Iowa City, Iowa, USA.
Am J Med Genet B Neuropsychiatr Genet. 2008 Jul 5;147B(5):565-70. doi: 10.1002/ajmg.b.30778.
In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus. In order to examine the role of methylation at this locus, we performed quantitative methylation analysis across the promoter region of this gene in lymphoblast lines derived from 191 subjects participating in the Iowa Adoption Studies (IAS). We analyzed the resulting data with respect to genotype and lifetime symptom counts for the more common major behavioral disorders in the IAS, antisocial personality disorder (ASPD), and substance use disorders (alcohol (AD) and nicotine dependence (ND)). We found that methylation status was significantly associated with lifetime symptom counts for ND (P < 0.001) and AD (P < 0.008) in women, but not men. Furthermore, a trend was found for women homozygous for the 3,3 allele to have a higher degree of overall methylation than women homozygous for the 4,4 allele (P < 0.10). We conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order.
近年来，诸如甲基化等表观遗传现象在介导行为疾病易感性方面的作用日益受到重视。单胺氧化酶A（MAOA）基因座被认为是表观遗传现象发挥作用的一个重要位点。为了研究该基因座甲基化的作用，我们对来自191名参与爱荷华收养研究（IAS）的受试者的淋巴母细胞系中该基因启动子区域进行了定量甲基化分析。我们根据IAS中较常见的主要行为障碍、反社会人格障碍（ASPD）和物质使用障碍（酒精依赖（AD）和尼古丁依赖（ND））的基因型和终生症状计数分析了所得数据。我们发现，甲基化状态与女性ND（P < 0.001）和AD（P < 0.008）的终生症状计数显著相关，但与男性无关。此外，发现3,3等位基因纯合的女性比4,4等位基因纯合的女性总体甲基化程度更高（P < 0.10）。我们得出结论，MAOA的甲基化可能在常见精神疾病中起重要作用，因此有必要对该基因座的表观遗传过程进行进一步研究。
