Introduction: A previous epigenome-wide association study causally linked DNA methylation (DNAm) at NFATC2IP gene (cg26663590) on body mass index (BMI). However, whether DNAm at NFATC2IP is associated with cardiovascular health (CVH) is unknown.

Methods: We included 408 participants from the POUNDs Lost trial. DNAm was profiled by sequencing method at baseline. Regional DNAm at NFATC2IP was defined as the average methylation level over ± 250 bp of cg26663590. We calculated the clinical CVH score at baseline, 6 months, and 2 years, combining BMI, blood pressure, total cholesterol, and fasting glucose. A higher score indicates better CVH.

Results: Regional DNAm at NFATC2IP was significantly associated with improvement in clinical CVH across 2 years (Figure). Participants within the highest tertile of regional DNAm at NFATC2IP had a greater improvement in clinical CVH score, compared to those within the lowest tertile (β [SE]: 0.68 [0.11] vs. 0.49 [0.10], p=0.028) at 6 months. Such association remained significant at 2 years (T3 vs. T1: 0.55 [0.13] vs. 0.23 [0.12], p=0.03). Moreover, higher regional DNAm at NFATC2IP was associated with greater reductions in total cholesterol (β [SE] per SD: -3.94 [1.34], p=0.004) and low-density lipoprotein cholesterol (β [SE] per SD: -3.26 [1.20], p=0.007) at 6 months.

Conclusion: Individuals with a higher regional DNAm level at NFATC2IP benefit more in the improvement of CVH.

Disclosure

X.Li: None. X.Shao: None. M.Kou: None. Q.Xue: None. G.Bray: Advisory Panel; Medifast, Inc., Herbalife International of America, Inc. F.Sacks: None. L.Qi: None.

Funding

National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024); National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383); Fogarty International Center (TW010790)

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