Background: Nearly 30% of U.S. adults are hypertensive with a high prevalence existing among Black Americans (42%). Exposure to psychosocial stress has been identified as a risk factor for hypertension and may explain part of the observed racial disparities. One pathway through which stress exposure may mechanistically alter biological functioning in a manner that affects risk of hypertension is via epigenetic modifications in hypertension-related genes, but this area remains understudied.
Aims and Hypothesis: In the present study, we investigate the relationship between stress exposure and methylation of 25 genes that have been associated with blood pressure in Blacks in previous genetic research. We hypothesize that stress exposure is associated with DNA methylation of blood pressure related genes.
Methods: We conducted an epigenetic association study using data from the ongoing InterGEN Study, a longitudinal investigation of the psychological, environmental, and genetic factors that contribute to hypertension risk in African American mothers (n=74) and their young children. Stress exposure was measured using the 24-item Stress Overload Scale (α=0.95), and a summary score was calculated by summing the Likert scale responses. Methylation was measured using the Illumina Infinium MethylationEPIC Beadchip, and M-values (i.e. log2 ratio of the intensities of methylated probe versus unmethylated probe) were calculated for association analysis. Linear regression was employed to assess the association between stress exposure and methylation in the a priori defined genes.
Results: At p<0.05, we identified 45 methylation sites associated with stress overload. These sites represented 17 of the 25 investigated genes. The most statistically significant sites were related to the genes: insulin like growth factor binding protein 3 (IGFBP3), calcium voltage-gated channel subunit alpha1 H (CACNA1H), and solute carrier family 4 member 5 (SLC4A5) (p=0.001, p=0.002, and p=0.006, respectively).
Conclusion: This study provides biological insight into DNA methylation as a mechanism whereby exposure to psychosocial stress affects risk of hypertension in Black women. Additional replication studies with a larger sample size and includes men are needed to validate and generalize the findings. Future research should further investigate the biological mediators between DNA methylation and hypertension manifestation.