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. 2023 Jun;80(6):1223-1230.
doi: 10.1161/HYPERTENSIONAHA.123.20864. Epub 2023 Apr 11.

DNA Methylation of Birthweight-Blood Pressure Genes and Changes of Blood Pressure in Response to Weight-Loss Diets in the POUNDS Lost Trial

Minghao Kou  1 , Xiang Li  1 , Xiaojian Shao  2 , Elin Grundberg  3 , Xuan Wang  1 , Hao Ma  1 , Yoriko Heianza  1 , J Alfredo Martinez  4 , George A Bray  5 , Frank M Sacks  6 , Lu Qi  1   6
Affiliations

DNA Methylation of Birthweight-Blood Pressure Genes and Changes of Blood Pressure in Response to Weight-Loss Diets in the POUNDS Lost Trial

Minghao Kou et al. Hypertension. 2023 Jun.

Abstract

Background: DNA methylation (DNAm) may play a critical role in bridging prenatal adverse events and cardiometabolic disorders including hypertension in later life.

Methods: We included 672 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss dietary intervention study. We defined the regional DNAm levels as the average methylation level of 5'-cytosine-phosphate-guanine-3' within 500 bp of LINC00319 (cg01820192), ATP2B1 (cg00508575), and LMNA (cg12593793), respectively. Generalized linear regression models were used to assess the association between the regional DNAm and 2-year blood pressure changes. Trajectory analysis was used to identify subgroups that shared a similar underlying trajectory of 2-year blood pressure changes.

Results: The regional DNAm at LINC00319, showed significantly different associations with 2-year changes in systolic blood pressure and diastolic blood pressure among participants assigned to low- or high-fat diets (P for interaction<0.05 for all). In response to the low-fat diet, per SD higher regional DNAm at LINC00319 was associated with greater reductions in both 2-year changes in systolic blood pressure (β, -1.481; P=0.020) and diastolic blood pressure (β, -1.096; P=0.009). Three trajectories of changes in systolic blood pressure or diastolic blood pressure were identified, and participants with higher regional DNAm at LINC00319 were more likely to experience and maintain decreased systolic blood pressure and diastolic blood pressure (odds ratio of being in decrease-stable versus stable [95% CI], 1.542 [1.146-2.076] and 1.463 [1.125-1.902]).

Conclusions: Our findings suggest that DNAm could be a metabolic memory bridging early and later life, and an indicator of more benefits from eating a low-fat weight-loss diet.

Keywords: DNA methylation; blood pressure; diet; obesity; weight-loss.

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Conflict of interest statement

Disclosures None.

Figures

Figure 1.
Figure 1.
24-month changes of blood pressure according to DNA methylation levels at LINC00319 in response to low-fat and high-fat diet. (A) 24-month SBP change by continuous DNA methylation; (B) 24-month DBP change by continuous DNA methylation; (C) 24-month SBP change by tertiles of DNA methylation; (D) 24-month DBP change by tertiles of DNA methylation.
Figure 2.
Figure 2.
Mean blood pressure according to months from baseline by three trajectories. (A) SBP; (B) DBP.
See this image and copyright information in PMC

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