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首页> 美国卫生研究院文献>Epigenetics >Impact of folic acid fortification on global DNA methylation and one-carbon biomarkers in the Womens Health Initiative Observational Study cohort
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Impact of folic acid fortification on global DNA methylation and one-carbon biomarkers in the Womens Health Initiative Observational Study cohort

机译：妇女健康倡议观察研究队列中叶酸强化对全球DNA甲基化和一碳生物标志物的影响

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DNA methylation is an epigenetic mechanism that regulates gene expression and can be modified by one-carbon nutrients. The objective of this study was to investigate the impact of folic acid (FA) fortification of the US food supply on leukocyte global DNA methylation and the relationship between DNA methylation, red blood cell (RBC) folate, and other one-carbon biomarkers among postmenopausal women enrolled in the Women's Health Initiative Observational Study. We selected 408 women from the highest and lowest tertiles of RBC folate distribution matching on age and timing of the baseline blood draw, which spanned the pre- (1994–1995), peri- (1996–1997), or post-fortification (1998) periods. Global DNA methylation was assessed by liquid chromatography-tandem mass spectrometry and expressed as a percentage of total cytosine. We observed an interaction (P = 0.02) between fortification period and RBC folate in relation to DNA methylation. Women with higher (vs. lower) RBC folate had higher mean DNA methylation (5.12 vs. 4.99%; P = 0.05) in the pre-fortification period, but lower (4.95 vs. 5.16%; P = 0.03) DNA methylation in the post-fortification period. We also observed significant correlations between one-carbon biomarkers and DNA methylation in the pre-fortification period, but not in the peri- or post-fortification period. The correlation between plasma homocysteine and DNA methylation was reversed from an inverse relationship during the pre-fortification period to a positive relationship during the post-fortification period. Our data suggest that (1) during FA fortification, higher RBC folate status is associated with a reduction in leukocyte global DNA methylation among postmenopausal women and; (2) the relationship between one-carbon biomarkers and global DNA methylation is dependent on folate availability.
机译：DNA甲基化是调节基因表达的表观遗传机制，可以被一碳营养素修饰。这项研究的目的是调查美国食品供应中叶酸（FA）强化对白细胞总体DNA甲基化的影响以及绝经后DNA甲基化，红细胞（RBC）叶酸和其他一碳生物标记之间的关系妇女参加了妇女健康倡议观察研究。我们从RBC叶酸分布的最高和最低三分位数中选择了408名女性，这些女性年龄与基线抽血的年龄和时间相匹配，涵盖了强化前（1994-1995年），外周（1996-1997年）或强化后（1998年） ）期间。通过液相色谱-串联质谱法评估总体DNA甲基化，并表示为总胞嘧啶的百分比。我们观察到强化期和RBC叶酸之间的相互作用（P = 0.02）与DNA甲基化有关。 RBC叶酸含量较高（相对较低）的女性在强化前平均DNA甲基化水平较高（5.12比4.99％； P = 0.05），但平均水平较低（4.95比5.16％； P = 0.03）。强化后时期。我们还观察到强化前的一碳生物标记物与DNA甲基化之间存在显着的相关性，而强化前后则没有。血浆同型半胱氨酸与DNA甲基化之间的相关性从强化前的逆相关逆转为强化后的正相关。我们的数据表明：（1）在FA强化期间，较高的RBC叶酸状态与绝经后女性白细胞总体DNA甲基化减少有关；以及（2）一碳生物标记物与全球DNA甲基化之间的关系取决于叶酸的有效性。

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