학술논문

Prenatal Multivitamin Use and MTHFR Genotype Are Associated with Newborn Cord Blood DNA Methylation
Document Type
article
Source
International Journal of Environmental Research and Public Health. 17(24)
Subject
Reproductive Medicine
Biomedical and Clinical Sciences
Genetics
Biological Sciences
Pediatric
Human Genome
Prevention
Nutrition
Clinical Research
Perinatal Period - Conditions Originating in Perinatal Period
2.1 Biological and endogenous factors
Aetiology
Reproductive health and childbirth
Good Health and Well Being
Child
DNA Methylation
Female
Fetal Blood
Genotype
Humans
Infant
Newborn
Male
Methylenetetrahydrofolate Reductase (NADPH2)
Pregnancy
Vitamins
DNA methylation
multivitamin
MTHFR
cord blood
Toxicology
Language
Abstract
BackgroundFetal 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 (MTHFR) is important for processing the nutrient folate.HypothesisWe hypothesize that supplement intake before pregnancy and maternal genotype are associated with DNA methylation in newborns.MethodsIn 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 MTHFR C677T allele.ResultsMaternal preconceptional multivitamin intake was associated with cord blood methylation, dependent on maternal MTHFR genotype (interaction term p = 0.013). For mothers without the MTHFR variant allele, multivitamin intake was associated with 0.96% (95% CI: 0.09, 1.83) higher global cord blood methylation (p = 0.04) and was also associated with the cumulative density distribution of methylation (p = 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 (p = 0.37).ConclusionsWe 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.