title: Periconception maternal smoking and low education are associated with methylation of INSIGF in children at the age of 17 months.
abstract: Maternal smoking during pregnancy and a low socioeconomic status (SES) lead to increased risks of adverse pregnancy outcome. Maternal education is often used as proxy for SES. We explored the programming of the insulin pathway genes IGF2 DMR (insulin growth factor 2 differentially methylated region), IGF2R (insulin growth factor 2 receptor) and INSIGF [the overlapping region of IGF2 and insulin (INS)] in the child through any periconception maternal smoking and education level. In 120 children at 17 months of age, methylation of DNA derived from white blood cells was measured. Periconception smoking and low education were independently associated with INSIGF methylation and showed a relative increase in methylation of +1.3%; P = 0.043 and +1.6%; P = 0.021. Smoking and low education showed an additive effect on INSIGF methylation (+2.8%; P = 0.011). There were no associations with IGF2 DMR and IGF2R methylation. Our data suggest that periconception maternal smoking and low education are associated with epigenetic marks on INSIGF in the very young child, this warrants further study in additional populations.
authors.affiliation: 1 Department of Obstetrics and Gynaecology, Eramus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: S A
authors.initials: SA
authors.lastname: Obermann-Borst
authors.affiliation: 2 Department of Molecular Epidemiology, LUMC, University Medical Centre, Leiden, The Netherlands.
authors.forename: B T
authors.initials: BT
authors.lastname: Heijmans
authors.affiliation: 4 Department of Biostatistics, Eramus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: P H C
authors.initials: PH
authors.lastname: Eilers
authors.affiliation: 2 Department of Molecular Epidemiology, LUMC, University Medical Centre, Leiden, The Netherlands.
authors.forename: E W
authors.initials: EW
authors.lastname: Tobi
authors.affiliation: 1 Department of Obstetrics and Gynaecology, Eramus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: E A P
authors.initials: EA
authors.lastname: Steegers
authors.affiliation: 2 Department of Molecular Epidemiology, LUMC, University Medical Centre, Leiden, The Netherlands.
authors.forename: P E
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: 1 Department of Obstetrics and Gynaecology, Eramus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: R P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000328:Adult; D019175:DNA Methylation; D004522:Educational Status; D044127:Epigenesis, Genetic; D005260:Female; D005807:Genes, Overlapping; D006801:Humans; D007223:Infant; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D016014:Linear Models; D008297:Male; D050506:Mutant Chimeric Proteins / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D012959:Socioeconomic Factors
chemical_list: C584675:INS-IGF2 protein, human; D007328:Insulin; D050506:Mutant Chimeric Proteins; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II