4.5 Article

Methylation of the C19MC microRNA locus in the placenta: association with maternal and chilhood body size

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INTERNATIONAL JOURNAL OF OBESITY
卷 44, 期 1, 页码 13-22

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NATURE PUBLISHING GROUP
DOI: 10.1038/s41366-019-0450-9

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资金

  1. Spanish Ministry of Education, Culture and Sport [CAS14/00011]
  2. Carlos III National Institute of Health (ISCIII) [CD15-00162]
  3. Generalitat de Catalunya [SLT002/16/00065]
  4. pFIS contract from ISCIII
  5. Ministerio de Ciencia e Innovacion, Instituto de Salud Carlos III (ISCIII), Madrid, Spain [PI17/00557, PI13/01257, PI16/01335]
  6. FEDER (Fondo Europeo de Desarrollo Regional)
  7. Fondation pour la Recherche Medicale (Equipes FRM) [DEQ31703]
  8. MRC [G0600717] Funding Source: UKRI

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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 (beta from -0.294 to -0.371; R-2 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 (beta from -0.428 to -0.552; R-2 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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