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

Abstract

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.

Keywords: AGA; C/EBP α; CAAT-enhancer binding protein alpha; DNA methylation; DOHaD; Epigenetics; GWG; LEP; LGA; Leptin; Leptin promoter DNA methylation; Maternal obesity; Pregnancy; SD; SGA; SNP; SP1; Std.Error; adequate for gestational age; developmental origins of adult health and disease; gestational weight gain; large for gestational age; large for gestational age, BMI, body mass index; rs2167270; single nucleotide polymorphism; small for gestational age; specificity protein; standard deviation; standard error.