Placental lipoprotein lipase DNA methylation levels are associated with gestational diabetes mellitus and maternal and cord blood lipid profiles

Abstract

Placental lipoprotein lipase (LPL) is crucial for placental lipid transfer. ImpairedLPLgene expression and activity were reported in pregnancies complicated by gestational diabetes mellitus (GDM) and intra-uterine growth restriction. We hypothesized that placentalLPLDNA methylation is altered by maternal metabolic status and could contribute to fetal programming. The objective of this study was thus to assess whether placentalLPLDNA methylation is associated with GDM and both maternal and newborn lipid profiles. Placenta biopsies were sampled at delivery from 126 women including 27 women with GDM diagnosed following a post 75 g-oral glucose tolerance test (OGTT) between weeks 24 and 28 of gestation. PlacentalLPLDNA methylation and expression levels were determined using bisulfite pyrosequencing and quantitative real-time PCR, respectively. DNA methylation levels withinLPLproximal promoter region (CpG1) and intron 1 CpG island (CpGs 2 and 3) were lower in placenta of women with GDM. DNA methylation levels atLPL-CpG1 and CpG3 were also negatively correlated with maternal glucose (2-h post OGTT;r=–0.22;P=0.02) and HDL-cholesterol levels (third trimester of pregnancy;r=–0.20;p=0.03), respectively. Moreover, we report correlation betweenLPL-CpG2 DNA methylation and cord blood lipid profile. DNA methylation levels within intron 1 CpG island explained up to 26% (r⩽–0.51;P<0.001) of placentalLPLmRNA expression variance. Overall, we showed that maternal metabolic profile is associated with placentalLPLDNA methylation dysregulation. Our results suggest that site-specificLPLepipolymorphisms in the placenta are possibly functional and could potentially be involved in determining the future metabolic health of the newborn.