Early life adversity and cardiovascular responses to repeated stress among adolescents: Moderating role of COMT gene rs4680 polymorphism*

Background: Early life adversity (ELA) increases the risk of cardiovascular diseases through dysregulation of cardiovascular stress responses manifested by either exaggerated or blunted reactivity. The catechol-Omethyltransferase (COMT) gene rs4680 polymorphism has been identified in gene-environment interaction (GxE) studies to explain individual differences in the effects of ELA on physiological stress responses. However, little is known about whether ELA interacts with COMT gene rs4680 polymorphism to affect cardiovascular responses to repeated stress exposures. Objective: The current study examined the associations between ELA and cardiovascular responses to repeated stress exposures, and the moderating role of COMT rs4680 polymorphism in these associations. Methods: The childhood trauma questionnaire (CTQ) was administered to 359 junior school students who underwent a two-successive stress exposures protocol with continuous cardiovascular monitoring [heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP)] across four laboratory phases, and their saliva samples for deoxyribonucleic acid (DNA) genotyping were collected. Results: ELA was associated with blunted HR reactivity to the first and second stress exposures, blunted SBP reactivity to the first stress exposure, and attenuated SBP habituation to repeated stress exposures. Moreover, COMT rs4680 moderated these associations, such that the associations between ELA and blunted HR, SBP, and DBP reactivity to the first stress and disrupted DBP habituation to repeated stress exposures only existed in GA/ AA genotype carriers but not in GG genotype carriers. Conclusions: These findings suggest that the A allele of COMT rs4680 is vulnerable to the negative effects of ELA on the developmental dysregulation of stress physiological systems.