Hypomethylation of the LEP Gene in Placenta and Elevated Maternal Leptin Concentration in Early Onset Pre-Eclampsia

Mol Cell Endocrinol. 2013 Mar 10;367(1-2):64-73. doi: 10.1016/j.mce.2012.12.018. Epub 2012 Dec 26.

Abstract

In pre-eclampsia, placental leptin is up-regulated and leptin is elevated in maternal plasma. To investigate potential epigenetic regulation of the leptin (LEP) gene in normal and complicated pregnancy, DNA methylation was assessed at multiple reported regulatory regions in placentae from control pregnancies (n=111), and those complicated by early onset pre-eclampsia (EOPET; arising <34 weeks; n=19), late onset pre-eclampsia (LOPET; arising ≥34 weeks; n=18) and normotensive intrauterine growth restriction (nIUGR; n=13). The LEP promoter was hypomethylated in EOPET, but not LOPET or nIUGR placentae, particularly at CpG sites downstream of the transcription start site (-10.1%; P<0.0001). Maternal plasma leptin was elevated in EOPET and LOPET (P<0.05), but not nIUGR, compared with controls. EOPET cases showed a trend towards biallelic LEP expression rather than skewed allelic expression observed in control placentae, suggesting that loss of normal monoallelic expression at the LEP locus is associated with hypomethylation, leading to increased overall LEP expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Alleles
  • Base Sequence
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Female
  • Gestational Age
  • Humans
  • Leptin / blood*
  • Leptin / genetics*
  • Molecular Sequence Data
  • Placenta / metabolism*
  • Polymorphism, Single Nucleotide / genetics
  • Pre-Eclampsia / blood*
  • Pre-Eclampsia / genetics*
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / genetics
  • Pregnancy Trimester, Third / genetics
  • Promoter Regions, Genetic / genetics

Substances

  • 5' Untranslated Regions
  • Leptin