Association Between Aggressive Behavior and Rs6267 Functional Polymorphism in the COMT Gene: the Moderating Effect of Gender and Negative Life Events

Abstract

The development of aggressive behavior has important genetic underpinning. With the advancement of molecular genetics, research on the mechanism underlying aggressive behavior has reached the molecular level in recent years. A number of recent studies have identified the COMT (Catechol-O-methyltransferase) gene, which is located on q11.2, as one of the candidate genes related to aggressive behavior. Catechol-Omethyltransferase (COMT) is one of the enzymes that degrade catecholamine neurotransmitters including dopamine. Recent research has discovered a new functional single nucleotide polymorphism (SNP) rs6267 in the COMT gene, but its possible association with aggressive behavior remains to be examined. Meanwhile, although animal studies have consistently observed an increased level of aggressive behavior among COMT knockout mice, research findings on human subjects have not been always consistent and even contradictory in some cases. It is assumed that the inconsistencies reported in previous studies may be due to the variance of gender rations and also the individual differences in life experiences of the samples in previous studies. In addition, most of the previously reported findings were obtained on subjects who were patients with schizophrenia, bipolar I disorder or ADHD. The present study aimed to extend the previous research by examining the association between rs6267 polymorphism and aggressive behavior among healthy adolescents, with particular focus on the moderating effect of gender and negative life events on the association. The subjects of this study were 153 grade 7-9 adolescents (male = 81, female = 72) of high aggressive behavior group (n = 65) and lower aggressive behavior group (n= 88). The subjects status of aggressive behavior were identified via adolescent's self-rating on the aggressive behavior questionnaire (Achenbach, 1991a; = 0.82) and validated via teacher assessment. DNA was extracted from saliva and genotype at rs6267 was performed for each participant in real time with MassARRAY RT software version 3.0.0.4 and analyzed using the MassARRAY Typer software version 3.4 (Sequenom). Data analysis was performed using the Statistical Package for Social Sciences 17.0 (SPSS 17.0), and a series of logistic regression analyses were conducted to aggressive behavior distributions. Two major findings were obtained from this study: (1) rs6267 polymorphism was significantly associated with the risk of aggressive behavior, but this association was observed only among males, with male adolescents with T allele possessing a decreased risk of aggressive behavior; while such an association was not observed among females. (2) There existed a marginal moderating effect of negative life events on the association between rs6267 polymorphism and aggressive behavior. Compared with adolescents carrying T allele, adolescents carrying GG genotype had an increased risk of aggressive behavior, but this difference only existed among adolescents who reported high level of negative life events. The present study lends further support for the theory that catecholamines may play an important role in adolescent aggressive behavior, and thereby contributes to COMT gene-aggression literature by elaborating the moderating effect of gender and negative life events among healthy adolescents. (PsycINFO Database Record (c) 2012 APA, all rights reserved) (journal abstract). 26809