title: A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity.
abstract: This study presents preliminary evidence of an association between polymorphic variation in the gene for monoamine oxidase-A (MAOA) and interindividual variability in aggressiveness, impulsivity and central nervous system (CNS) serotonergic responsivity. An apparently functional 30-bp VNTR in the promoter region of the X-chromosomal MAOA gene (MAOA-uVNTR), as well as a dinucleotide repeat in intron 2 (MAOA-CAn), was genotyped in a community sample of 110 men. All participants had completed standard interview and questionnaire measures of impulsivity, hostility and lifetime aggression history; in a majority of subjects (n=75), central serotonergic activity was also assessed by neuropsychopharmacologic challenge (prolactin response to fenfluramine hydrochloride). The four repeat variants of the MAOA-uVNTR polymorphism were grouped for analysis (alleles '1+ 4' vs. '2+3') based on prior evidence of enhanced transcriptional activity in MAOA promoter constructs with alleles 2 and 3 (repeats of intermediate length). Men in the 1/4 allele group scored significantly lower on a composite measure of dispositional aggressiveness and impulsivity (P<0.015) and showed more pronounced CNS serotonergic responsivity (P<0.02) than men in the 2/3 allele group. These associations were also significant on comparison of the more prevalent one and three alleles alone (encompassing 93% of subjects). Although in linkage disequilibrium with the MAOA-uVNTR polymorphism, MAOA-CAn repeat length variation did not vary significantly with respect to behavior or fenflluramine challenge in this sample. We conclude that the MAOA-uVNTR regulatory polymorphism may contribute, in part, to individual differences in both CNS serotonergic responsivity and personality traits germane to impulse control and antagonistic behavior.
authors.affiliation: Department of Psychology, Behavioral Physiology Laboratory, University of Pittsburgh, PA 15260, USA. manuck@pitt.edu
authors.forename: S B
authors.initials: SB
authors.lastname: Manuck
authors.forename: J D
authors.initials: JD
authors.lastname: Flory
authors.forename: R E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: J J
authors.initials: JJ
authors.lastname: Mann
authors.forename: M F
authors.initials: MF
authors.lastname: Muldoon
mesh_terms: D000328:Adult; D000374:Aggression / Q000502:physiology*; D000483:Alleles; D001921:Brain / Q000503:physiopathology*; D018900:Dinucleotide Repeats / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005809:Genes, Regulator / Q000235:genetics*; D005838:Genotype; D006791:Hostility; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D008995:Monoamine Oxidase / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011985:Receptors, Serotonin / Q000235:genetics* / Q000502:physiology; D012701:Serotonin / Q000502:physiology
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin; D008995:Monoamine Oxidase