出生时的表观遗传时钟与儿童期血压轨迹：一项前瞻性出生队列研究。

Epigenetic Clock at Birth and Childhood Blood Pressure Trajectory: A Prospective Birth Cohort Study.

机构信息

Department of Epidemiology (J.H., A.Y.M., F.B.H., L.L.), Harvard T.H. Chan School of Public Health, Boston, MA.

Center for Genomic Medicine and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.H.).

出版信息

Hypertension. 2024 Oct;81(10):e113-e124. doi: 10.1161/HYPERTENSIONAHA.124.22695. Epub 2024 Aug 1.

DOI:10.1161/HYPERTENSIONAHA.124.22695

PMID:39087326

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11410530/

Abstract

BACKGROUND

The impact of methylation gestational age (GAmAge; a biomarker of fetal maturity) at birth on childhood blood pressure (BP) trajectories is unknown.

METHODS

This cohort study included 500 boys and 440 girls with data on cord blood DNA methylation and BP at 3 to 15 years of age. Systolic BP (SBP) and diastolic BP percentiles were calculated based on clinical guidelines. Time-series K-means clustering identified 4 distinct SBP and diastolic BP percentile trajectories: high-steady, high-decrease, normal-increase, and normal-steady. GAmAge was estimated using an existing pediatric epigenetic clock. Extrinsic age acceleration was calculated as residuals of associations between GAmAge and chronological gestational age. Intrinsic age acceleration was calculated using the same method adjusting for cord blood cell compositions.

RESULTS

Extrinsic age acceleration and intrinsic age acceleration were inversely associated with repeated measures of BP percentiles. Significant inverse associations were observed between extrinsic age acceleration and SBP percentiles in boys (β=-2.02; =0.02) but not in girls (β=-0.49; =0.58). Both extrinsic age acceleration and intrinsic age acceleration were inversely associated with SBP percentiles in girls born preterm (<37 weeks; β=-2.95; β=-3.00; <0.05). Compared with the normal-steady SBP trajectory, significant inverse associations were observed between intrinsic age acceleration and high-steady, high-decrease, and normal-increase SBP trajectories in boys (odds ratio, 0.73-0.81; <0.03), and significant positive associations were observed for high-decrease and normal-increase SBP trajectories in girls (odds ratio, 1.26-1.38; <0.01). Significant sex differences were observed (<2×10).

CONCLUSIONS

GAmAge acceleration at birth was inversely associated with child BP, and such association was more pronounced in boys than in girls. Our findings may shed new light on the developmental origins of high BP and sex differences in cardiovascular risk.

摘要

背景

出生时甲基化胎龄（GAmAge；胎儿成熟的生物标志物）对儿童血压（BP）轨迹的影响尚不清楚。

方法

本队列研究纳入了 500 名男孩和 440 名女孩，他们的数据包括脐带血 DNA 甲基化和 3 至 15 岁时的 BP。根据临床指南计算收缩压（SBP）和舒张压百分位数。时间序列 K-均值聚类确定了 4 种不同的 SBP 和舒张压百分位数轨迹：高稳定、高下降、正常升高和正常稳定。使用现有的儿科表观遗传时钟估算 GAmAge。外源性年龄加速是通过 GAmAge 与胎龄的关联残差计算得出的。内源性年龄加速是使用相同的方法计算得出的，该方法调整了脐带血细胞成分。

结果

外源性年龄加速和内源性年龄加速与 BP 百分位数的重复测量呈负相关。在男孩中，外源性年龄加速与 SBP 百分位数呈显著负相关（β=-2.02；=0.02），但在女孩中则无显著相关性（β=-0.49；=0.58）。在外源性年龄加速和内源性年龄加速方面，出生时胎龄<37 周的女孩的 SBP 百分位数均与 SBP 百分位数呈负相关（β=-2.95；β=-3.00；<0.05）。与正常稳定的 SBP 轨迹相比，在男孩中，内源性年龄加速与高稳定、高下降和正常升高的 SBP 轨迹呈显著负相关（比值比，0.73-0.81；<0.03），而在女孩中，高下降和正常升高的 SBP 轨迹与内源性年龄加速呈显著正相关（比值比，1.26-1.38；<0.01）。观察到显著的性别差异（<2×10）。