Evaluation of Methylation Status of the eNOS Promoter at Birth in Relation to Childhood Bone Mineral Content
- 8 December 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Calcified Tissue International
- Vol. 90 (2), 120-127
- https://doi.org/10.1007/s00223-011-9554-5
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
This publication has 41 references indexed in Scilit:
- Enhancers regulate progression of development in mammalian cellsNucleic Acids Research, 2011
- Epigenetic Gene Promoter Methylation at Birth Is Associated With Child’s Later AdiposityDiabetes, 2011
- Maternal predictors of neonatal bone size and geometry: the Southampton Women’s SurveyJournal of Developmental Origins of Health and Disease, 2009
- Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studiesNature Genetics, 2009
- Effect of 27nt Small RNA on Endothelial Nitric-Oxide Synthase ExpressionMolecular Biology of the Cell, 2008
- Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPARα promoter of the offspringBritish Journal of Nutrition, 2008
- Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1JCI Insight, 2008
- Parasympathetic response in chick myocytes and mouse heart is controlled by SREBPJCI Insight, 2008
- Maternal Size in Pregnancy and Body Composition in ChildrenJournal of Clinical Endocrinology & Metabolism, 2007
- Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modificationsBritish Journal of Nutrition, 2007