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Calcified Tissue International

, Volume 90, Issue 2, pp 120–127 | Cite as

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
Original Research

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.

Keywords

Epigenesis Methylation Umbilical cord eNOS DXA 

Notes

Acknowledgement

We thank the mothers and their children who gave us their time, and a team of dedicated research nurses and ancillary staff for their assistance. This work was supported by grants from the Medical Research Council; British Heart Foundation; Arthritis Research Campaign; National Osteoporosis Society; International Osteoporosis Foundation; Cohen Trust; Southampton NIHR Biomedical Research Unit in Nutrition, Diet and Lifestyle; and NIHR Musculoskeletal Biomedical Research Unit, University of Oxford. Participants were drawn from a cohort study funded by the Medical Research Council and the Dunhill Medical Trust. We thank Ms. G. Strange for helping to prepare the manuscript.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Nicholas C. Harvey
    • 1
  • Karen A. Lillycrop
    • 2
  • Emma Garratt
    • 2
  • Allan Sheppard
    • 3
    • 4
  • Cameron McLean
    • 3
    • 4
  • Graham Burdge
    • 2
  • Jo Slater-Jefferies
    • 2
  • Joanne Rodford
    • 2
  • Sarah Crozier
    • 1
  • Hazel Inskip
    • 1
  • Bright Starling Emerald
    • 7
  • Catharine R. Gale
    • 1
  • Mark Hanson
    • 2
  • Peter Gluckman
    • 3
    • 5
  • Keith Godfrey
    • 1
    • 2
    • 6
  • Cyrus Cooper
    • 1
  1. 1.MRC Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK
  2. 2.Southampton Institute of Developmental SciencesUniversity of SouthamptonSouthamptonUK
  3. 3.Liggins InstituteUniversity of AucklandAucklandNew Zealand
  4. 4.AgResearchRuakura Research CentreHamiltonNew Zealand
  5. 5.Singapore Institute for Clinical SciencesSingaporeSingapore
  6. 6.Southampton NIHR Biomedical Research Unit in Nutrition, Diet and LifestyleUniversity of SouthamptonSouthamptonUK
  7. 7.Department of Anatomy, Faculty of Medicine and Health SciencesUAE UniversityAl ainUnited Arab Emirates

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