Tissue-specific Leptin promoter DNA methylation is associated with maternal and infant perinatal factors

Leptin a regulator of body weight is involved in reproductive and developmental functions. Leptin promoter DNA methylation (LEP) regulates gene expression in a tissue-specific manner and has been linked to adverse pregnancy outcomes. In non-pathologic human pregnancies, we assessed LEP methylation, genotyped the single nucleotide polymorphism (SNP) rs2167270 in placental (n = 81), maternal and cord blood samples (n = 60), and examined the association between methylation, genotype, and perinatal factors. Maternal blood LEP methylation was lower in pre-pregnancy obese women (P = 0.01). Cord blood LEP methylation was higher in small for gestational age (SGA) (P = 4.6 × 10−3) and A/A genotype (P = 1.6 × 10−4), lower (−1.47, P = 0.03) in infants born to pre-pregnancy obese mothers and correlated (P = 0.01) with maternal blood LEP. Gender was associated with placental LEP methylation (P = 0.05). These results suggest that LEP epigenetic control may be influenced by perinatal factors including: maternal obesity, infant growth, genotype and gender in a tissue-specific manner and may have multigenerational implications.