Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

OBJECTIVE: In epidemiological studies, adverse early-life conditions associate with subsequent cardiometabolic disease. Hypothesized causes include maternal malnutrition, foetal glucocorticoid overexposure and reduced growth factors. Animal studies suggest a role for epigenetic processes in maintaining early-life effects into adulthood, but human relevance is unknown. We aimed to investigate relationships between an unbalanced maternal diet in pregnancy, neonatal and adult anthropometric variables with methylation at key genes controlling tissue glucocorticoid action and foetal growth. DESIGN: We studied 34 individuals aged 40 from the Motherwell cohort study whose mothers ate an unbalanced diet in pregnancy, previously linked with elevated blood pressure and cortisol in adult offspring. MEASUREMENTS: DNA methylation at 11β-hydroxysteroid dehydrogenase type 2 (HSD2), glucocorticoid receptor (GR) and insulin-like growth factor 2 (IGF2) was measured by pyrosequencing on buffy coat DNA. RESULTS: Methylation at specific CpGs in the HSD2 promoter and at one of the IGF2 differentially methylated regions (H19 ICR) correlated with neonatal anthropometric variables. CpG methylation within HSD2, GR and H19 ICR was positively associated with increased adiposity and blood pressure in adulthood. Methylation at GR (exon 1F) was increased in offspring of mothers with the most unbalanced diets in pregnancy. CONCLUSIONS: Alterations in DNA methylation at genes important in regulating circulating cortisol levels, tissue glucocorticoid action, blood pressure and foetal growth are present in adulthood in association with both early-life parameters and cardiometabolic risk factors. The data indicate a persisting epigenetic link between early-life maternal diet and/or foetal growth and cardiovascular disease risk in humans.

Type

Journal article

Journal

Clinical endocrinology

Publication Date

12/2012

Volume

77

Pages

808 - 815

Addresses

Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.

Keywords

Humans, Prenatal Exposure Delayed Effects, Birth Weight, Hydrocortisone, 11-beta-Hydroxysteroid Dehydrogenase Type 2, Insulin-Like Growth Factor II, Receptors, Glucocorticoid, DNA, Glucocorticoids, Anthropometry, DNA Methylation, Epigenesis, Genetic, Fetal Development, Pregnancy, Maternal-Fetal Exchange, Blood Pressure, Adult, Infant, Newborn, Female, Maternal Nutritional Physiological Phenomena