Distinct promoter methylation and isoform-specific expression of RASFF1A in placental biopsies from complicated pregnancies.

INTRODUCTION

Epigenetic changes in the placenta have been postulated to act as mediators between environmental influences and poor fetal growth. We assessed if genes with a plausible influence on growth could be aberrantly methylated in placental samples from pregnancies complicated by intrauterine growth restriction (IUGR).

METHODS

A candidate gene approach was undertaken using a custom Illumina Goldengate® array on a collection of placental samples from growth restricted pregnancies and normally grown controls with confirmation using bisulphite pyrosequencing.

RESULTS

The custom array analysis revealed that the promoter of RASSF1A was the only region with significant methylation differences between IUGR placentas and those from pregnancies with appropriate growth for gestational age (AGA). The RASSF1A promoter had increased levels of DNA methylation in IUGR samples compared to controls. Interestingly, the methylation difference was also observed in preeclamptic samples. Higher methylation was associated with a concomitant decrease in expression of the RASSF1 transcript A, but not other isoforms that originate from an alternative, nearby promoter interval.

DISCUSSION: Our results do not support the hypothesis that altered DNA-methylation in the placenta is a mechanism generally involved in fetal growth restriction. A specific region corresponding to the promoter of RASSF1A does display methylation changes in placenta that could be used to identify at-risk pregnancies.