title: Gene environment interactions with a novel variable Monoamine Oxidase A transcriptional enhancer are associated with antisocial personality disorder.
abstract: 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.
authors.affiliation: Department of Psychiatry, The University of Iowa, Iowa City, IA, USA. robert-philibert@uiowa.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Philibert
authors.forename: Pamela
authors.initials: P
authors.lastname: Wernett
authors.forename: Jeff
authors.initials: J
authors.lastname: Plume
authors.forename: Hans
authors.initials: H
authors.lastname: Packer
authors.forename: Gene H
authors.initials: GH
authors.lastname: Brody
authors.forename: Steven R H
authors.initials: SR
authors.lastname: Beach
mesh_terms: D000328:Adult; D000483:Alleles; D000987:Antisocial Personality Disorder / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D008995:Monoamine Oxidase