孕期补充维生素D3对出生时胎龄后代表观遗传时钟的影响:一项随机对照试验的事后分析

Effects of Maternal Vitamin D3 Supplementation on Offspring Epigenetic Clock of Gestational Age at Birth: A Post-hoc Analysis of a Randomized Controlled Trial.

作者信息

Chen Li, Wagner Carol L, Dong Yanbin, Wang Xiaoling, Shary Judith R, Huang Ying, Hollis Bruce W, Zhu Haidong

机构信息

Georgia Prevention Institute, Department of Medicine, Medical College of Georgia, Augusta University , Augusta, GA, USA.

Department of Pediatrics, Medical University of South Carolina ,SC, USA.

出版信息

Epigenetics. 2020 Aug;15(8):830-840. doi: 10.1080/15592294.2020.1734148. Epub 2020 Mar 1.

Abstract

Vitamin D could be beneficial for healthy ageing in humans. We previously found that vitamin D supplementation may slow down epigenetic ageing in young African American adults. We tested new epigenetic clocks developed for neonates among a multiethnic population, and tested the hypothesis that maternal vitamin D supplementation would slow down the epigenetic gestational age acceleration (GAA) in newborn babies. Ninety-two pregnant women (aged 29.6 ± 4.8 y; 21% African Americans, 28% Hispanics) were randomized to receive 4000 IU/day vitamin D or placebo, plus prenatal vitamins containing 400 IU vitamin D during pregnancy in a randomized controlled trial (RCT). Cord blood genome-wide methylation analysis was performed on the Illumina Infinium MethylationEPIC Beadchip. DNA methylation gestational age was calculated based on two calculations developed by Knight and Bohlin. DNA methylation gestational ages calculated by Knight's clock and Bohlin' clock were highly correlated with the gestational age in the placebo group (correlation coefficients = 0.88, s< 0.001, respectively). GAA was associated with higher birth weight ( = 0.039). In the entire cohort, vitamin D supplementation was not associated with GAA ( > 0.05). However, vitamin D supplementation decreased GAA by both Knight's clock (β = -0.89, = 0.047) and Bohlin's clock (β = -0.71, = 0.005) in the African American participants. Maternal vitamin D supplementation may slow down the epigenetic gestational ageing process in African American neonates. Long-term follow-up studies are warranted to determine the role of epigenetic age acceleration in the growth and development of offspring.

摘要

维生素D可能对人类健康衰老有益。我们之前发现,补充维生素D可能会减缓年轻非裔美国成年人的表观遗传衰老。我们在一个多民族人群中测试了为新生儿开发的新表观遗传时钟,并检验了母亲补充维生素D会减缓新生儿表观遗传胎龄加速(GAA)这一假设。在一项随机对照试验(RCT)中,92名孕妇(年龄29.6±4.8岁;21%为非裔美国人,28%为西班牙裔)被随机分配接受4000国际单位/天的维生素D或安慰剂,孕期还补充含400国际单位维生素D的产前维生素。在Illumina Infinium MethylationEPIC Beadchip上进行脐带血全基因组甲基化分析。DNA甲基化胎龄是根据奈特和博林开发的两种计算方法计算得出的。在安慰剂组中,通过奈特时钟和博林时钟计算的DNA甲基化胎龄与胎龄高度相关(相关系数分别为0.88,P<0.001)。GAA与较高的出生体重相关(P=0.039)。在整个队列中,补充维生素D与GAA无关(P>0.05)。然而,在非裔美国参与者中,补充维生素D通过奈特时钟(β=-0.89,P=0.047)和博林时钟(β=-0.71,P=0.005)均降低了GAA。母亲补充维生素D可能会减缓非裔美国新生儿的表观遗传胎龄衰老过程。有必要进行长期随访研究,以确定表观遗传年龄加速在后代生长发育中的作用。

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