Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content

Nicholas C. Harvey, Karen A. Lillycrop, Emma Garratt, Allan Sheppard, Cameron McLean, Graham Burdge, Jo Slater-Jefferies, Joanne Rodford, Sarah Crozier, Hazel Inskip, Bright Starling Emerald, Catharine R. Gale, Mark Hanson, Peter Gluckman, Keith Godfrey, Cyrus Cooper

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year-old children. We used Sequenom MassARRAY to assess the methylation status of two CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument). Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553 +, after taking account of age and sex, there were strong positive associations between methylation status and the child's whole-body bone area (r = 0.28, P = 0.02), bone mineral content (r = 0.34, P = 0.005), and areal bone mineral density (r = 0.34, P = 0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass. Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development.

Original languageEnglish
Pages (from-to)120-127
Number of pages8
JournalCalcified Tissue International
Volume90
Issue number2
DOIs
Publication statusPublished - Feb 2012

Keywords

  • DXA
  • Epigenesis
  • Methylation
  • Umbilical cord
  • eNOS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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