Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Int J Environ Res Public Health. 2020 Dec 9;17(24):9190. doi: 10.3390/ijerph17249190.
Fetal development involves cellular differentiation and epigenetic changes-complex processes that are sensitive to environmental factors. Maternal nutrient levels during pregnancy affect development, and methylene tetrahydrofolate reductase () is important for processing the nutrient folate.
We hypothesize that supplement intake before pregnancy and maternal genotype are associated with DNA methylation in newborns.
In the pregnancy cohort, Early Autism Risk Longitudinal Investigation (EARLI), health history, and genotype information was obtained (n = 249 families). Cord blood DNA methylation (n = 130) was measured using the Illumina HumanMethylation450k array and global DNA methylation levels were computed over 455,698 sites. Supplement use preconception and during pregnancy were surveyed at visits during pregnancy. We evaluated associations between maternal preconception supplement intake and global DNA methylation or DNA methylation density distributions of newborn cord blood, stratified by the presence of a variant maternal C677T allele.
Maternal preconceptional multivitamin intake was associated with cord blood methylation, dependent on maternal genotype (interaction term = 0.013). For mothers without the variant allele, multivitamin intake was associated with 0.96% (95% CI: 0.09, 1.83) higher global cord blood methylation ( = 0.04) and was also associated with the cumulative density distribution of methylation ( = 0.03). For mothers with at least one variant allele, multivitamin intake had a null -0.06% (95% CI: -0.45, 0.33) association with global cord blood DNA methylation, and was not associated with the cumulative density distribution ( = 0.37).
We observed that cord blood DNA methylation was associated with maternal supplement exposure preconception and maternal genotype. Genetic context should be considered when assessing DNA methylation effects of modifiable risk factors around the time of pregnancy.
胎儿发育涉及细胞分化和表观遗传变化——这些复杂的过程对环境因素敏感。母亲在怀孕期间的营养水平会影响发育，亚甲基四氢叶酸还原酶（）对于处理营养叶酸很重要。
我们假设孕前补充剂的摄入和母体基因型与新生儿的 DNA 甲基化有关。
在妊娠队列早期自闭症风险纵向研究 (EARLI) 中，获得了健康史和基因型信息（n = 249 个家庭）。使用 Illumina HumanMethylation450k 阵列测量脐带血 DNA 甲基化（n = 130），并计算了 455698 个位点的全基因组 DNA 甲基化水平。在怀孕期间的访问中调查了孕前和怀孕期间的补充剂使用情况。我们评估了母体孕前补充剂摄入与新生儿脐带血全基因组 DNA 甲基化或 DNA 甲基化密度分布之间的关系，按存在变异母体 C677T 等位基因进行分层。
母体孕前多种维生素摄入与脐带血甲基化有关，取决于母体基因型（交互项 = 0.013）。对于没有变异等位基因的母亲，多种维生素摄入与 0.96%（95%CI：0.09，1.83）更高的全球脐带血甲基化（= 0.04）相关，并且与甲基化的累积密度分布相关（= 0.03）。对于至少有一个变异等位基因的母亲，多种维生素摄入与全球脐带血 DNA 甲基化的关联呈零 -0.06%（95%CI：-0.45，0.33），与累积密度分布无关（= 0.37）。
我们观察到脐带血 DNA 甲基化与母体补充剂暴露于孕前和母体基因型有关。在评估与妊娠前后可改变的风险因素有关的 DNA 甲基化效应时，应考虑遗传背景。
