DNA methylation in essential hypertension in young adults in east coast Malaysia

Abstract

Hypertension is emerging as the most prevalent risk factor of ischemic heart disease in young adults, but awareness is low in this age group. The prevalence of prehypertension in this population is also high, putting them at higher cardiovascular risk. The pathophysiology of essential hypertension has yet to be fully understood, and epigenetic modifications have been proposed to play some role. To date, very few epigenetic studies were done in young adults with prehypertension and hypertension. The aim of this study was to compare the level of DNA methylation in the promoter of implicated genes in young adults with normotensive blood pressure, prehypertension and hypertension. An observational cross-sectional study was conducted among 240 subjects age 18 to 45 years in Kuantan, Pahang, Malaysia. Eighty subjects were recruited for each blood pressure group; normotension, prehypertension, and hypertension as defined by the Ministry of Health Malaysia Clinical Practice Guidelines 4th edition. MethyLight analysis was performed to determine DNA methylation levels of IL-6, ADD1 and AGTR1 gene promoter in the blood. Differentially methylated genes in prehypertension and/or hypertension group were followed by gene expression study (n = 10 per group). There was no significant difference in IL-6 methylation between hypertensive and normotensive. IL-6 predicted prehypertension in males (p = 0.014), but not females. Hypertensive and prehypertensive males, and prehypertensive females, had lower ADD1 methylation than their respective normotensive counterparts. After adjusting for other covariates, ADD1 methylation predicted prehypertension and hypertension in males (p = 0.002 and p = 0.034 respectively). There was no significant difference in AGTR1 methylation between the three groups in both sexes. There was no significant association between IL-6 and ADD1 methylation level and gene expression level. DNA methylation of IL-6 and ADD1 are independent predictors of prehypertension and/or hypertension in males hence has potential as an adjunct biomarker for risk stratification or disease progression. This is the pioneering study of IL-6, ADD1 and AGTR1 methylation in prehypertensive and hypertensive young adults. Further study to delineate potential mechanisms linking DNA methylation to disease development is warranted.