title: Early life lipid profile and metabolic programming in very young children.
abstract: OBJECTIVE
  Lipid derangements during early postnatal life may induce stable epigenetic changes and alter metabolic programming. We investigated associations between serum lipid profiles in very young children and DNA methylation of tumor necrosis factor-alpha (TNFα) and leptin (LEP). Secondly, we explored if the maternal serum lipid profile modifies DNA methylation in the child.
  
  
  RESULTS
  In 120 healthy children at 17 months of age, DNA methylation of TNFα and LEP was measured in DNA derived from whole blood. Linear mixed models were used to calculate exposure-specific differences and associations. Total cholesterol in children was associated with decreased methylation of TNFα (-5.8%, p = 0.036), and HDL-cholesterol was associated with decreased methylation of both TNFα (-6.9%, p = 0.013) and LEP (-3.4%, p = 0.021). Additional adjustment for gestational age at birth, birth weight, sex, breastfeeding and educational level attenuated the effects, TNFα (-6.1%, p = 0.058) and LEP (-3.1%, p = 0.041). In mothers, HDL-cholesterol only was associated with decreased methylation of TNFα in the child (-8.7%, p = 0.001).
  
  
  CONCLUSIONS
  Our data support the developmental origin of health and disease hypothesis by showing that total cholesterol and HDL-cholesterol levels in very young children are associated with epigenetic metabolic programming, which may affect their vulnerability for developing cardiovascular diseases in later life.
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: K P J
authors.initials: KP
authors.lastname: Wijnands
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: S A
authors.initials: SA
authors.lastname: Obermann-Borst
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: r.steegers@erasmusmc.nl.
authors.forename: R P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000367:Age Factors; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D050171:Dyslipidemias / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007223:Infant; D020738:Leptin / Q000235:genetics*; D016014:Linear Models; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D009035:Mothers; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005819:Genetic Markers; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol
keywords: DNA methylation; Early postnatal life; Leptin; Lipids; Metabolic programming; TNFα