Abstract 11963: Blood Level of Coffee-Eelated DNA Methylation and Long-Term Changes in Blood Pressure in Response to Weight-Loss Diet Interventions: The Pounds Lost Trial

Abstract

Introduction: Coffee intake has been associated with a lower risk of hypertension. Recent epigenome-wide association studies linked DNA methylation (DNAm) at PHGDH (cg14476101) with coffee consumption and blood pressure, which may explain the mechanism underlying coffee intake and blood pressure. However, little is known about whether the coffee-related DNAm is associated with long-term changes in blood pressure in response to dietary weight-loss interventions. Hypothesis: We hypothesized that participants with varying coffee-related DNAm levels may respond differently to dietary weight-loss interventions on long-term changes in blood pressure. Methods: The current study included 669 participants with overweight/obesity, who were randomly assigned to 1 of 4 diets varying in macronutrient components. Blood DNAm levels were profiled by a high-resolution methylC-capture sequencing at baseline. The regional DNAm at PHGDH was defined as the average methylation level over CpGs within ±250 bp of cg14476101. Two-year changes in blood pressure were calculated. Linear regression models were used to examine the associations between DNAm at PHDGH and 2-year changes in blood pressure in response to dietary weight-loss interventions, adjusting for age, race, sex, body mass index, anti-hypertensive medications, and concurrent weight loss. Results: Regional DNAm at PHDGH was not associated with 2-year changes in blood pressure in the total population. We found significant interactions between regional DNAm at PHDGH and dietary protein intake on 2-year changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p-interaction=0.018 and 0.005, respectively). Among participants assigned to an average-protein diet (15% of energy intake), higher baseline regional DNAm at PHDGH was associated with greater reductions in SBP (beta [SE]: -9.7 [3.4], p=0.005) and DBP (beta [SE]: -6.5 [2.4], p=0.007); while no association was observed among those assigned to a high-protein diet (25% of energy intake; p=0.40 for SBP, p=0.15 for BP). Conclusion: Our data indicate that participants with a higher regional DNAm level at PHDGH benefited more in long-term improvement in blood pressure when consuming an average-protein weight-loss diet.