Functional Polymorphisms in the Serotonin 1B Receptor Gene (HTR1B) Predict Self-reported Anger and Hostility Among Young Men

Objective To examine associations between haplotypes of the serotonin 1B receptor gene and individual differences in anger and hostility. Methods Data were analyzed from a study of 361 university students (47% male). Participants were genotyped at 5 polymorphisms in the HTR1B gene (rs11568817, rs130058, rs6296, rs6297, rs13212041), including promoter and 3′UTR polymorphisms with opposite functional effects on gene expression. Participants reported their emotional states across 30 consecutive days for up to four years. Haplotype pairs were constructed statistically and assigned to a level of HTR1B expression based on the presence of the functional polymorphisms. Results Six haplotypes accounted for \u3e97% of chromosomes. Three low expression haplotypes contained the 3′UTR variant (rs13212041 A-allele) that enables a microRNA-mediated reduction in expression. One intermediate expression haplotype contained the 3′UTR A-allele paired with the high-activity promoter. Two high expression haplotypes contained the 3′UTR variant (rs13212041 G-allele) that attenuates microRNA-mediated reduction in expression. Men with low expression haplotypes reported greater anger and hostility than men with one or two high expression haplotypes. Diplotype classification accounted for 8.4% of the variance in men’s anger and hostility, primarily due to the 3′UTR polymorphism (rs13212041), but with some contribution of the functional promoter combination (rs11568817, rs130058). Associations with anger and hostility were not found in women. Conclusions These findings extend our understanding of the genetic basis of anger and hostility by showing that newly characterized HTR1B haplotypes, particularly those with rs13212041, which modulates microRNA-mediated regulation of HTR1B expression, may have important implications for aggression-related phenotypes among young men