Cognitive benefits of folic acid supplementation during pregnancy track with epigenetic changes at an imprint regulator
Notice bibliographique
Résumé
BACKGROUND: The human ZFP57 gene is a major regulator of imprinted genes, maintaining DNA methylation marks that distinguish parent-of-origin-specific alleles. DNA methylation of the gene itself has shown sensitivity to environmental stimuli, particularly folate status. However, the role of DNA methylation in ZFP57's own regulation has not been fully investigated. METHODS: We used samples and data from our previously described randomised controlled trial (RCT) in pregnancy called Folic Acid Supplementation in the Second and Third Trimester (FASSTT), including follow-up of the children at age 11. Biometric and blood biochemistry results were examined for mothers and children. Methylation of ZFP57 was analysed by EPIC arrays, pyrosequencing and clonal analysis, and transcription assessed by PCR-based methods. Functional consequences of altered methylation were examined in cultured cells with mutations or by inhibition of the main DNA methyltransferases. DNA variants were examined using pyrosequencing and Sanger sequencing, with results compared to published studies using bioinformatic approaches. Cognitive outcomes were assessed using the Wechsler Intelligence Scale for Children 4th UK Edition (WISC-IV), with neural activity during language tasks quantified using magnetoencephalography (MEG). RESULTS: Here we show that methylation at an alternative upstream promoter of ZFP57 is controlled in part by a quantitative trait locus (QTL). By altering DNA methylation levels, we demonstrate that this in turn controls the expression of the ZFP57 isoforms. Methylation at this region is also sensitive to folate levels, as we have previously shown in this cohort. Fully methylated alleles were associated with poorer performance in the Symbol Search and Cancellation subtests of WISC-IV in the children at age 11 years. There were also differences in neural activity during language tasks, as measured by MEG. Analysis of published genome-wide studies indicated other SNPs in linkage disequilibrium with the mQTL were also associated with neurodevelopmental outcomes. CONCLUSIONS: While numbers in the current RCT were small and require further validation in larger cohorts, the results nevertheless suggest a molecular mechanism by which maternal folic acid supplementation during pregnancy may help to counteract the effects of folate depletion and positively influence cognitive development in the offspring.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».