First trimester vitamin D status and placental epigenomics in preeclampsia among Northern Plains primiparas.

Abstract

As maternal vitamin D status has been associated with preeclampsia, the purpose of this study was to determine variations in DNA methylation patterns and associated protein expression in placental genes regulating vitamin D metabolism. A convenience sample of 48 pregnant nulliparous women, including 11 later diagnosed with preeclampsia, were recruited in this prospective study. Using a case-control design in two groups of women, we administered a food frequency questionnaire to determine vitamin D dietary intake. Laboratory measures included serum vitamin D levels (25[OH]D), DNA methylation patterns and protein expression in placental genes regulating vitamin D metabolism (1α-hydroxylase, CYP27B1; vitamin D receptor, VDR; retinoid X receptor, RXR) from placental tissue collected at delivery among those diagnosed with preeclampsia and those who remained normotensive throughout pregnancy. There were no significant differences in vitamin D dietary intake or mean serum 25[OH]D levels, although the proportion of women with deficient 25[OH]D levels was higher in the preeclampsia group (46%) than the normotensive group (20%). Placenta samples from women with preeclampsia also had increased DNA methylation of CYP27B1, VDR and RXR genes with lower protein expression levels limited to RXR. Hypermethylation of key placental genes involved in vitamin D metabolism suggests uncoupling of processes that may interfere with placentation and availability of vitamin D at the maternal-fetal interface.