Abstract
Numerous studies have demonstrated that both catechol-O-methyltransferase (COMT) gene and monoamine oxidase A (MAOA) gene have been involved in aggressive behavior, as have stressful life events (SLEs). However, most of available evidence was based upon single gene or single gene–environment design, which is limited in accounting for the variance of aggressive behavior, a complex phenotype. This study examined the possible gene × gene × environment interactions between SLE (interpersonal problems and academic pressure) and two genetic polymorphisms (MAOA T941G and COMT Ala22/72Ser) correlated with aggressive behaviors in a sample of 658 Chinese male adolescents. Mothers and teachers reported on adolescents’ aggressive behavior using Achenbach’s Child Behavior Checklist and Teacher Report Form, respectively. Adolescents completed Self-Rating Life Events Checklist. Saliva samples were collected for DNA analysis. The results revealed no main effects of MAOA T941G and COMT Ala22/72Ser polymorphisms on male adolescents’ aggressive behaviors. However, a two-way interactive effect of interpersonal problems and MAOA T941G genotype on teacher-reported aggressive behavior was observed: adolescents with lower activity of MAOA T allele, but not those with MAOA G allele, exhibited greater aggressive behavior with an increase in interpersonal problems. A three-way interaction among COMT Ala22/72Ser and MAOA T941G polymorphisms, and SLE in the academic pressure on aggressive behavior was also identified. Among adolescents with lower activity of COMT GT/TT genotype and MAOA T allele, the higher level of academic pressure was significantly linked with an amplification of aggressive behavior, whereas this association didn’t exist among those with other genotypes. The present study presents the first evidence of COMT × MAOA × SLE interaction effect on male adolescents’ aggressive behavior, highlights the importance of considering distinct domains of stressful events and information bias when examining the effect of MAOA and COMT on aggressive behavior, and thereby contributes to MAOA gene-aggression and COMT gene-aggression literature.
Highlights
Aggressive behavior is a common externalized problem behavior which exerts a short-term and long-term negative effects on the development of adolescents (Ritakallio et al, 2005; Card et al, 2008)
There were no significant correlations between COMT Ala22/72Ser polymorphism, MAOA T941G polymorphism and each measure of SLEs, suggesting no gene–environment correlations
Our findings highlight the importance of examining the multi-genes by environment interaction on aggressive behavior and afford some explanations for the inconsistence of the findings from previous studies concerning the effects of COMT gene or MAOA gene on aggressive behavior
Summary
Aggressive behavior is a common externalized problem behavior which exerts a short-term and long-term negative effects on the development of adolescents (Ritakallio et al, 2005; Card et al, 2008). It should be noted that among Asians, including Chinese populations from which the current study’s sample was drawn, a second common functional single nucleotide polymorphism at which the variant between a G and T causes an alanine -to-serine (Ala/Ser) substitution, exists in exon 4 This Ala/Ser variation was associated with a more dramatic reduction in COMT enzyme activity than the most studied Val/Met polymorphism, COMT Ala22/72Ser polymorphism (rs6267) is not found in Caucasian or African American populations, who all (as far as is known) carry the alanine allele at this locus (Lee et al, 2005; Hong et al, 2008; Wang, 2009). A few of studies have found that a serine substitution at rs6267 was significantly associated with increased aggressive behavior (Hong et al, 2008; Wang and Zhang, 2010), there seems to be a long way to go given less research on gene–environment interaction has targeted this variant by far
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