Abstract 475: Catechol-O-Methyl Transferase Methylation and Blood Pressure in Children Treated With Second-generation Antipsychotics

Abstract

Second-generation antipsychotics (SGA) are increasingly being used to treat children for a wide-range of mental health conditions, and are associated with cardiometabolic side effects such as rapid weight gain and elevated blood pressure (BP). The catechol-O-methyl transferase ( COMT) Val158Met variant is associated with BP in the general population. We recently reported higher BP in SGA-treated children with the Met allele, but no such association in SGA-naïve children. Methylation of the COMT promoter is another important regulatory factor governing COMT activity. The aim of this study was to investigate the interaction of the COMT Val158Met variant and COMT methylation on BP in children with mental health conditions. A cross-sectional population of SGA-treated (n=106) and SGA[[Unable to Display Character: –]]naïve children (n=122), ≤18 y of age, were assessed for markers of cardiometabolic health. Bisulfite pyrosequencing was used to quantify the methylation status of three CpG sites in the COMT promoter. Relationships between SGA treatment, COMT Val158Met genotype and COMT promoter methylation were assessed using general linear models. BMI was standardized for age and sex (zBMI) and systolic and diastolic BP standardized for age, sex, and height (zSBP, zDBP). When analyzed as one group, there were no significant effects of COMT genotype, SGA-treatment, or mental health diagnosis on mean methylation. In SGA-treated children, an interaction between mean methylation and COMT genotype was observed for zSBP ( p =0.015), where zSBP was positively related to methylation in children with the Val/Val genotype, but not in children with the Met allele. After adjustments for ethnicity, SGA-duration, and zBMI the effect was diminished ( p =0.109), with SGA-duration ( p =0.018) and zBMI ( p =0.032) accounting for the variation in zSBP. This association was not found in SGA-naïve children. These findings suggest COMT promoter methylation may influence the effect of the COMT Val158Met variant on blood pressure in SGA-treated children.