Abstract
Among the genetic variations in the monoamine oxidase A (MAOA) gene, upstream variable number tandem repeats (uVNTRs) of the promoter have been associated with individual differences in human physiology and aggressive behaviour. However, the evidence for a molecular or neural link between MAOA uVNTRs and aggression remains ambiguous. Additionally, the use of inconsistent promoter constructs in previous studies has added to the confusion. Therefore, it is necessary to demonstrate the genetic function of MAOA uVNTR and its effects on multiple aspects of aggression. Here, we identified three MAOA alleles in Koreans: the predominant 3.5R and 4.5R alleles, as well as the rare 2.5R allele. There was a minor difference in transcriptional efficiency between the 3.5R and 4.5R alleles, with the greatest value for the 2.5R allele, in contrast to existing research. Psychological indices of aggression did not differ among MAOA genotypes. However, our electroencephalogram and electrocardiogram results obtained under aggression-related stimulation revealed oscillatory changes as novel phenotypes that vary with the MAOA genotype. In particular, we observed prominent changes in frontal γ power and heart rate in 4.5R carriers of men. Our findings provide genetic insights into MAOA function and offer a neurobiological basis for various socio-emotional mechanisms in healthy individuals.
Highlights
Among the genetic variations in the monoamine oxidase A (MAOA) gene, upstream variable number tandem repeats of the promoter have been associated with individual differences in human physiology and aggressive behaviour
In vitro gene fusion and transfection assays initially indicated that MAOA upstream variable number tandem repeats (uVNTRs) variants may cause differential transcription of the MAOA mRNA; the 2-repeat (2R) and 3-repeat (3R) low-MAOA (L-MAOA) alleles are associated with lower transcriptional efficiency than the 4-repeat (4R) high-MAOA (H-MAOA) allele, with corresponding lower enzyme expression and higher predicted downstream neurotransmitter levels[20,21,22,23]
Www.nature.com/scientificreports efficiency of monoamine oxidase A was inconsistent and depended on the transfected constructs[35]. These findings suggest that factors such as post-translational factors or the modulation of protein levels and activity, and possibly compensatory mechanisms between the different neurotransmitter systems regulated by MAOA, may work together in modulating the role of MAOA uVNTR genotype on aggression
Summary
Among the genetic variations in the monoamine oxidase A (MAOA) gene, upstream variable number tandem repeats (uVNTRs) of the promoter have been associated with individual differences in human physiology and aggressive behaviour. Www.nature.com/scientificreports efficiency of monoamine oxidase A was inconsistent and depended on the transfected constructs[35] These findings suggest that factors such as post-translational factors or the modulation of protein levels and activity, and possibly compensatory mechanisms between the different neurotransmitter systems regulated by MAOA, may work together in modulating the role of MAOA uVNTR genotype on aggression. The conflicting results obtained by different studies could be due to the broad role of MAOA in modulating different neurotransmitter systems, the heterogeneity in measuring neural function and human behaviour, the in vitro system used to measure the effect of uVNTR on MAOA expression, and to the effect of gene × environmental interactions[40,41,42,43]. It remains unclear whether MAOA is an X-inactivated gene, making it challenging to evaluate enzyme expression or activity in heterozygous genotypes[44]
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