We have previously reported lower plasma cytokines levels in aggressive subjects [32]. We therefore compared the methylation profiles of IL-1α, IL-6, IL-4, IL-10 and IL-8 gene loci and three of their transcription factors NFkB1, NFAT5 and STAT6 gene loci in adult males on a chronic physical aggression trajectory (CPA) between 6 and 15 years of age and males with the same background who followed a normal physical aggression trajectory (control group). Although the promoter area and the immediate 5′ regulatory regions play an important role in regulation of gene expression, it is also clear that methylation-dependent regulatory sequences could be found in other parts of the body of the gene or its flanking sequences. Most genome-wide DNA methylation screens focus on promoter regions for reasons of feasibility. By focusing on a short-list of selected genes we were able to examine the entire genomic loci of these genes using a combination of methylated DNA immunoprecipitation (MeDIP) and comprehensive high-density oligonucleotide arrays. Our study provides evidence for association between male physical aggression and differentially methylated regions in cytokines and their transcription factor genomic loci.
