Global DNA methylation and hypertension control Vis-À-Vis lipids: an exploratory population based study from rural...

Hypertension remains a major global health challenge, accounting for a substantial burden of mortality and morbidity. In India, despite advances in pharmacological management, optimal blood pressure (BP) control is still not achieved in a significant proportion of the population. Abnormal lipid profiles frequently coexist with hypertension, synergistically increasing the risk of cardiovascular diseases. Emerging evidence suggests that DNA methylation may mediate the effects of metabolic stressors on gene regulation, contributing to the pathophysiology of hypertension and related cardiometabolic disorders. This population-based study investigates the interrelationship between blood pressure, lipid profiles, and global 5-methylcytosine (5mC) levels across normotensive individuals, hypertensives identified by the investigators and not yet on medication, and hypertensives on medication (both controlled and uncontrolled). A total of 900 individuals (450 hypertensive cases and 450 age- and sex-matched controls) were recruited from rural Punjab. Anthropometric parameters (BMI, WC, HC), BP, lipid levels, and global DNA methylation were assessed using standardized protocols. Data were analyzed using SPSS v22. Findings revealed that abnormal levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were significantly higher among hypertensive individuals on medication with uncontrolled BP. These individuals also exhibited significantly lower global 5mC levels, indicating hypomethylation. The results suggest that a high lipid burden may not only compromise the efficacy of antihypertensive medication but also contribute to global DNA hypomethylation, which is often associated with accelerated biological aging and elevated cardiovascular risk. The study highlights the importance of lipids not in hypertension control but also in maintenance of Global DNA methylation.