ABSTRACT
CONTEXT: Histone modifications regulate gene expression; dysregulation has been linked with cardiovascular diseases. Associations between histone modification levels and blood pressure in humans are unclear. OBJECTIVE: We examine the relationship between global histone concentrations and various markers of blood pressure. MATERIALS AND METHODS: Using the Beijing Truck Driver Air Pollution Study, we investigated global peripheral white blood cell histone modifications (H3K9ac, H3K9me3, H3K27me3, and H3K36me3) associations with pre- and post-work measurements of systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP), and pulse pressure (PP) using multivariable mixed-effect models. RESULTS: H3K9ac was negatively associated with pre-work SBP and MAP; H3K9me3 was negatively associated with pre-work SBP, DBP, and MAP; and H3K27me3 was negatively associated with pre-work SBP. Among office workers, H3K9me3 was negatively associated with pre-work SBP, DBP, and MAP. Among truck drivers, H3K9ac and H3K27me were negatively associated with pre-work SBP, and H3K27me3 was positively associated with post-work PP. DISCUSSION AND CONCLUSION: Epigenome-wide H3K9ac, H3K9me3, and H3K27me3 were negatively associated with multiple pre-work blood pressure measures. These associations substantially changed during the day, suggesting an influence of daily activities. Blood-based histone modification biomarkers are potential candidates for studies requiring estimations of morning/pre-work blood pressure.
Subject(s)
Activities of Daily Living , Blood Pressure Determination/methods , Blood Pressure , Histone Code/physiology , Adolescent , Adult , Air Pollution , Beijing , Cardiovascular Diseases , Circadian Rhythm , Epigenomics , Humans , Middle Aged , Motor Vehicles , Young AdultABSTRACT
BACKGROUND: Blood pressure (BP) is a complex, multifactorial clinical outcome driven by genetic susceptibility, behavioral choices, and environmental factors. Many molecular mechanisms have been proposed for the pathophysiology of high BP even as its prevalence continues to grow worldwide, increasing morbidity and marking it as a major public health concern. To address this, we evaluated miRNA profiling in blood leukocytes as potential biomarkers of BP and BP-related risk factors. METHODS: The Beijing Truck Driver Air Pollution Study included 60 truck drivers and 60 office workers examined in 2008. On two days separated by 1-2 weeks, we examined three BP measures: systolic, diastolic, and mean arterial pressure measured at both pre- and post-work exams for blood NanoString nCounter miRNA profiles. We used covariate-adjusted linear mixed-effect models to examine associations between BP and increased miRNA expression in both pooled and risk factor-stratified analyses. RESULTS: Overall 43 miRNAs were associated with pre-work BP (FDR<0.05). In stratified analyses different but overlapping groups of miRNAs were associated with pre-work BP in truck drivers, high-BMI participants, and usual alcohol drinkers (FDR<0.05). Only four miRNAs were associated with post-work BP (FDR<0.05), in ever smokers. CONCLUSION: Our results suggest that many miRNAs were significantly associated with BP in subgroups exposed to known hypertension risk factors. These findings shed light on the underlying molecular mechanisms of BP, and may assist with the development of a miRNA panel for early detection of hypertension.