DNA methylation ofIGF2,GNASAS,INSIGFandLEPand being born small for gestational age

Being born small for gestational age (SGA), a proxy for intrauterine growth restriction (IUGR), and prenatal famine exposure are both associated with a greater risk of metabolic disease. Both associations have been hypothesized to involve epigenetic mechanisms. We investigated whether prenatal growth restriction early in pregnancy was associated with changes in DNA methylation at loci that were previously shown to be sensitive to early gestational famine exposure. We compared 38 individuals born preterm (-1SDS at 3 months post term; AGA). The SGA individuals were not only lighter at birth, but also had a smaller length (P=3.3x10 (-13) ) and head circumference at birth (P=4.1x10 (-13) ). The DNA methylation levels of IGF2, GNASAS, INSIGF and LEP were 48.5%, 47.5%, 79.4% and 25.7% respectively. This was not significantly different between SGA and AGA individuals. Risk factors for being born SGA, including preeclampsia and maternal smoking, were also not associated with DNA methylation at these loci. Growth restriction early in development is not associated with DNA methylation at loci shown to be affected by prenatal famine exposure. Our and previous results by others indicate that prenatal growth restriction and famine exposure may be associated with different epigenetic changes or non epigenetic mechanisms that may lead to similar later health outcomes.