母体受孕前叶酸补充与青少年后代的 DNA 甲基化模式。

Maternal Periconceptional Folic Acid Supplementation and DNA Methylation Patterns in Adolescent Offspring.

机构信息

National Center on Birth Defects and Developmental Disabilities, US CDC, Atlanta, GA, USA.

US CDC China Office, Beijing, China.

出版信息

J Nutr. 2023 Jan 14;152(12):2669-2676. doi: 10.1093/jn/nxac184.

DOI:10.1093/jn/nxac184

PMID:36196007

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9839994/

Abstract

BACKGROUND

Folate, including the folic acid form, is a key component of the one-carbon metabolic pathway used for DNA methylation. Changes in DNA methylation patterns during critical development periods are associated with disease outcomes and are associated with changes in nutritional status in pregnancy. The long-term impact of periconceptional folic acid supplementation on DNA methylation patterns is unknown.

OBJECTIVES

To determine the long-term impact of periconceptional folic acid supplementation on DNA methylation patterns, we examined the association of the recommended dosage (400 μg/d) and time period (periconceptional before pregnancy through first trimester) of folic acid supplementation with the DNA methylation patterns in the offspring at age 14-17 y compared with offspring with no supplementation.

METHODS

Two geographic sites in China from the 1993-1995 Community Intervention Program of folic acid supplementation were selected for the follow-up study. DNA methylation at 402,730 CpG sites was assessed using saliva samples from 89 mothers and 179 adolescents (89 male). The mean age at saliva collection was 40 y among mothers (range: 35-54 y) and 15 y among adolescents (range: 14-17 y). Epigenome-wide analyses were conducted to assess the interactions of periconceptional folic acid exposure, the 5,10-methylenetetrahydrofolate reductase (MTHFR)-C677T genotype, and epigenome-wide DNA methylation controlling for offspring sex, geographic region, and background cell composition in the saliva.

RESULTS

In the primary outcome, no significant differences were observed in epigenome-wide methylation patterns between adolescents exposed and those non-exposed to maternal periconceptional folic acid supplementation after adjustment for potential confounders [false discovery rate (FDR) P values < 0.05]. The MTHFR-C677T genotype did not modify this lack of association (FDR P values < 0.05).

CONCLUSIONS

Overall, there were no differences in DNA methylation between adolescents who were exposed during the critical developmental window and those not exposed to the recommended periconceptional/first-trimester dosage of folic acid.

摘要

背景

叶酸，包括叶酸形式，是用于 DNA 甲基化的一碳代谢途径的关键组成部分。在关键发育期，DNA 甲基化模式的变化与疾病结局有关，并与妊娠期间营养状况的变化有关。围孕期补充叶酸对 DNA 甲基化模式的长期影响尚不清楚。

目的

为了确定围孕期补充叶酸对 DNA 甲基化模式的长期影响，我们研究了推荐剂量（400μg/d）和补充时间（围孕期至妊娠早期）与未补充叶酸的后代 14-17 岁时的 DNA 甲基化模式之间的关系。

方法

从中国 1993-1995 年社区叶酸补充干预项目中选择了两个地理地点进行随访研究。使用来自 89 名母亲和 179 名青少年（89 名男性）的唾液样本评估了 402,730 个 CpG 位点的 DNA 甲基化。母亲采集唾液时的平均年龄为 40 岁（范围：35-54 岁），青少年为 15 岁（范围：14-17 岁）。进行全基因组表观遗传分析，以评估围孕期叶酸暴露、5,10-亚甲基四氢叶酸还原酶（MTHFR）-C677T 基因型与全基因组 DNA 甲基化之间的相互作用，同时控制唾液中后代性别、地理区域和背景细胞组成。