Abstract
Objectives
To study DNA methylation at the C19MC locus in the placenta and its association with (1) parental body size, (2) transmission of haplotypes for the C19MC rs55765443 SNP, and (3) offspring’s body size and/or body composition at birth and in childhood.
Subjects and methods
Seventy-two pregnant women-infant pairs and 63 fathers were included in the study. Weight and height of mothers, fathers and newborns were registered during pregnancy or at birth (n = 72). Placental DNA methylation at the C19MC imprinting control region (ICR) was quantified by bisulfite pyrosequencing. Genotyping of the SNP was performed using restriction fragment length polymorphisms. The children’s body size and composition were reassessed at age 6 years (n = 32).
Results
Lower levels of placental C19MC methylation were associated with increased body size of mother, specifically with higher pregestational and predelivery weights and height of the mother (β from –0.294 to –0.371; R2 from 0.04 to 0.10 and all p < 0.019), and with higher weight, height, waist and hip circumferences, and fat mass of the child (β from –0.428 to –0.552; R2 from 0.33 to 0.56 and all p < 0.009). Parental transmission of the SNP did not correlate with an altered placental methylation status at the C19MC ICR.
Conclusions
Increased maternal size is associated with reduced placental C19MC methylation, which, in turn, relate to larger body size of the child.
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Acknowledgements
The authors are grateful to all the children and parents who participated in the study. AP-P was granted with CAS14/00011 (Spanish Ministry of Education, Culture and Sport). SX-T holds a Sara Borrell contract from Carlos III National Institute of Health (ISCIII; CD15-00162). GC-B was granted a pFIS contract from ISCIII. BM-P holds a contract from Generalitat de Catalunya (SLT002/16/00065). JB is a Miguel Servet investigator from ISCIII (MS12/03239). FDZ is a Senior Investigator of the Clinical Research Fund of the Leuven University Hospital. LI is a Clinical Investigator of CIBERDEM (Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders) from ISCIII. AL-B is an I3 investigator (Spanish Ministry of Economy and Competitiveness). This study was supported by grants from the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (ISCIII), Madrid, Spain (PI17/00557 to JB, and PI13/01257 and PI16/01335 to AL-B), projects co-funded by FEDER (Fondo Europeo de Desarrollo Regional). RF and MG acknowledge grant funding from the Fondation pour la Recherche Médicale (Equipes FRM, grant number DEQ31703).
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Prats-Puig, A., Xargay-Torrent, S., Carreras-Badosa, G. et al. Methylation of the C19MC microRNA locus in the placenta: association with maternal and chilhood body size. Int J Obes 44, 13–22 (2020). https://doi.org/10.1038/s41366-019-0450-9
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DOI: https://doi.org/10.1038/s41366-019-0450-9
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