Abstract 035: Unique Associations of DNA Methylation With 24-Hour Blood Pressure Phenotypes in African Americans

Abstract

Blood pressure (BP) levels are influenced by genetic and environmental factors. Epigenome is the result of interactions between the DNA and the environment. Methylation is a naturally occurring epigenetic modification of genomic DNA and may influence BP levels. We examined the association of DNA methylation in whole blood with 24-hour and clinic BP phenotypes in 281 African Americans; fifty percent were women and fifty percent were hypertensive. Mean age of the participants was 44±7 years and mean body mass index (BMI) was 28±5 kg/m 2 . Clinic BP was obtained in duplicate from both arms and averaged using a standardized protocol as part of screening procedures for a 3-day inpatient clinical study. Blood was obtained for DNA at the time of screening visit. BP medications were discontinued for 1-week after the screening visit and prior to inpatient study. Detailed phenotyping and 24-hour BP measurements were performed during the in-patient study. DNA methylation profiles of these 281 subjects with 24-hour BP measurements were analyzed at single-base resolution with a modified reduced representation bisulfite sequencing (RRBS) method. Analysis of 38,216 DNA methylation regions, representing 1,549,368 CpG sites across the genome, identified up to 72 regions that were significantly associated with 24-hour, daytime or nighttime BPs. Considered jointly, these methylation regions explained up to 66.6% of the BP variance. Methylation regions associated with 24-hour, daytime or nighttime BPs or systolic, diastolic or mean arterial pressure or pulse pressure overlapped partially. No methylation region was significantly associated with clinic BP. Two to three methylation regions were significantly associated with 24-hour BP after adjustment for age, sex, and body mass index. These methylation regions, jointly, explained up to 16.5% of the variance of 24-hour BP, while age, sex and body mass index explained up to 11.0% of the variance. In summary, we have identified several DNA methylation regions in the whole blood that are associated with 24-hour, daytime or nighttime BPs, but not with clinic BP measured at a single point in time. DNA methylation appears to be an excellent marker for the cumulative effect of factors that influence 24-hour, daytime or nighttime BPs