Abstract P150: Dynamic Alu Cpg Methylation Change In Elevated Diastolic Blood Pressure

Abstract

Hypertension is recognized as age-related disease. However, its interaction with aging at the epigenetic level is still not fully understood. Hypomethylation of Alu elements, the most abundant class of interspersed repetitive sequence in the genome, is associated with global hypomethylation, an important epigenetic event of aging. Dermal fibroblasts have been observed to be affected by hypertension. In vitro study has shown that hypertension accelerated expression of age-related phenotypes. Therefore, in our study, we aimed to examine the relationship between blood pressure, age and Alu methylation status using dermal fibroblasts as a model. Biopsies of dermal fibroblasts were performed on 39 patients with various ages and blood pressure statuses. The patients were grouped into three categories based on their systolic blood pressure (SBP) and diastolic blood pressure (DBP): Normal (SBP = 130 mmHg; DBP = 85 mmHg), High Normal (SBP = 130-139 mmHg; DBP = 85-89 mmHg) and Hypertensive (SBP ≥ 140 mmHg; DBP ≥ 90 mmHg). Combined Bisulfite Restriction Analysis was performed to determine the Alu methylation level and pattern. The data was analyzed using Two Way ANOVA factoring in age groups. The Alu methylation level in the normal, high normal and hypertensive groups according to SBP is 30.3 ± 2.15%, 30.2 ± 2.15%, and 30.1 ± 2.06% and 29.6 ± 1.85%, 31.1 ± 1.78%, and 30.2 ± 2.48% according to DBP (data displaying in mean ± SD). The percentages of u C u C methylation pattern were 42.8 ± 5.57%, 42.7 ± 3.84%, 41.9 ± 4.84%, 44.2 ± 5.19%, 40.4 ± 2.95%, and 42.3 ± 4.79% for normal, high normal and hypertensive group, by SBP and DBP respectively. There were statistically significant differences between groups of DBP status with methylation level lowest in the high normal group. u C u C methylation pattern was the highest in high normal DBP group (p-value < 0.05). There was also a statistically significant interaction between age and DBP level to Alu methylation. However, there was no statistically significant difference between SBP groups. We conclude that there is a dynamic Alu methylation change in the elevation of DBP with overarching trend of Alu hypomethylation. This phenomenon suggests that Alu methylation may have a role in how hypertension accelerate cellular aging in different tissues.