Gene environment interactions with a novel variable Monoamine Oxidase A transcriptional enhancer are associated with antisocial personality disorder

Robert A Philibert; Pamela Wernett; Jeff Plume; Hans Packer; Gene H Brody; Steven R.H Beach

doi:10.1016/j.biopsycho.2011.04.007

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Gene environment interactions with a novel variable Monoamine Oxidase A transcriptional enhancer are associated with antisocial personality disorder

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Gene environment interactions with a novel variable Monoamine Oxidase A transcriptional enhancer are associated with antisocial personality disorder

Robert A Philibert, Pamela Wernett, Jeff Plume, Hans Packer, Gene H Brody and Steven R.H Beach

Biological psychology, Vol.87(3), pp.366-371

2011

DOI: 10.1016/j.biopsycho.2011.04.007

PMCID: PMC3134149

PMID: 21554924

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https://www.ncbi.nlm.nih.gov/pmc/articles/3134149View

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Abstract

► We describe a new MAOA VNTR and present in silico and in vitro evidence that it is functional. ► We show that analysis of G × E effects at this VNTR genotype better accounts for the presence of antisocial personality disorder (ASPD) in the Iowa Adoption Studies then G × E interactions at the previously characterized VNTR. 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.

Monoamine Oxidase A

Methylation

Antisocial personality

Polymorphism

Details

Title: Subtitle: Gene environment interactions with a novel variable Monoamine Oxidase A transcriptional enhancer are associated with antisocial personality disorder
Creators: Robert A Philibert - Department of Psychiatry, The University of Iowa, Iowa City, IA, USA
Pamela Wernett - Neuroscience and Genetics Programs, The University of Iowa, Iowa City, IA, USA
Jeff Plume - Neuroscience and Genetics Programs, The University of Iowa, Iowa City, IA, USA
Hans Packer - Neuroscience and Genetics Programs, The University of Iowa, Iowa City, IA, USA
Gene H Brody - The University of Georgia, Athens, GA, USA
Steven R.H Beach - The University of Georgia, Athens, GA, USA
Resource Type: Journal article
Publication Details: Biological psychology, Vol.87(3), pp.366-371
DOI: 10.1016/j.biopsycho.2011.04.007
PMID: 21554924
PMCID: PMC3134149
NLM abbreviation: Biol Psychol
ISSN: 0301-0511
eISSN: 1873-6246
Publisher: Elsevier B.V
Language: English
Date published: 2011
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984003444002771

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