Quantitative aberrations of hypermethylated RASSF1A gene sequences in maternal plasma in pre‐eclampsia

OBJECTIVE: To study if quantitative aberrations in circulating placental-derived hypermethylated RASSF1A DNA in maternal plasma are associated with pre-eclamptic pregnancies. METHOD: Maternal plasma and placental tissues from third-trimester pre-eclamptic women and gestational-age matched normotensive controls were studied. Real-time PCR was performed to quantify RASSF1A concentrations before and after methylation-sensitive restriction digestion in a duplex assay, where ss-actin concentrations were quantified as an internal control to confirm complete enzyme digestion. RESULTS: The median concentrations of hypermethylated RASSF1A were 4.3-fold higher in maternal plasma of pre-eclamptic subjects than in controls. There was no significant difference between the extent of RASSF1A hypermethylation in placental tissues obtained from pre-eclamptic and control pregnancies. CONCLUSION: This study demonstrated the potential utility of hypermethylated RASSF1A sequences in maternal plasma as a gender- and polymorphism-independent marker for pre-eclampsia.