UNCORRECTED PROOF 1 First trimester vitamin D status and placental epigenomics in 2 preeclampsia among Northern Plains primiparas 3 Q1 Cindy M. Anderson a, ⁎, Jody Ralph b , LuAnn Johnson c , Angela Scheett c , Michelle L. Wright d , 4 Jacquelyn Y. Taylor e , Joyce E. Ohm f , Eric Uthus c 5 a Q2 College of Nursing, The Ohio State University, Columbus, OH, United States 6 b College of Nursing and Professional Disciplines, University of North Dakota, Grand Forks, ND, United States 7 c Grand Forks Human Nutrition Research Center, Grand Forks, ND, United States 8 d Virginia Commonwealth University, Richmond, VA, United States 9 e Yale School of Nursing, Orange, CT, United States 10 f School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, United States abstract 11 article info 12 Article history: 13 Received 8 April 2014 14 Accepted 8 July 2014 15 Available online xxxx 16 Keywords: 17 DNA methylation 18 Gestational hypertension 19 Vitamin D 20 Aims: As maternal vitamin D status has been associated with preeclampsia, the purpose of this study was to 21 determine variations in DNA methylation patterns and associated protein expression in placental genes regulat- 22 ing vitamin D metabolism. 23 Main methods: A convenience sample of 48 pregnant nulliparous women, including 11 later diagnosed with 24 preeclampsia, were recruited in this prospective study. Using a case–control design in two groups of women, 25 we administered a food frequency questionnaire to determine vitamin D dietary intake. Laboratory measures 26 included serum vitamin D levels (25[OH]D), DNA methylation patterns and protein expression in placental 27 genes regulating vitamin D metabolism (1α-hydroxylase, CYP27B1; vitamin D receptor, VDR; retinoid X recep- 28 tor, RXR) from placental tissue collected at delivery among those diagnosed with preeclampsia and those who 29 remained normotensive throughout pregnancy. 30 Key findings: There were no significant differences in vitamin D dietary intake or mean serum 25[OH]D levels, 31 although the proportion of women with deficient 25[OH]D levels was higher in the preeclampsia group (46%) 32 than the normotensive group (20%). Placenta samples from women with preeclampsia also had increased DNA 33 methylation of CYP27B1, VDR and RXR genes with lower protein expression levels limited to RXR. 34 Significance: Hypermethylation of key placental genes involved in vitamin D metabolism suggests uncoupling of 35 processes that may interfere with placentation and availability of vitamin D at the maternal–fetal interface. 36 © 2014 Published by Elsevier Inc. 37 38 39 40 41 Introduction 42 Global and national trends demonstrate an overall increase in the 43 prevalence of vitamin D insufficiency in recent years (Ginde et al., 44 2009; Vandevijvere et al., 2012; Hossein-Nezhad and Holick, 2013). 45 Among women of reproductive age, hypovitaminosis D or inadequate 46 levels of vitamin D (below 30 ng/mL), has been linked to inadequate 47 dietary intake, reduced sun exposure and dark skin color (Bodnar 48 et al., 2007a; Nesby-O'Dell et al., 2002; Collins-Fulea et al., 2012). Evi- 49 dence among pregnant women indicates that changes in blood pressure 50 are influenced by seasonal variations, with blood pressures higher in 51 winter and lower during summer (Bodnar et al., 2006), suggesting a po- 52 tential association with maternal vitamin D status. Among women with 53 gestational diabetes, higher systolic and diastolic blood pressures were 54 associated with vitamin D insufficiency in pregnancy {{2241 Weinert, 55 L.S. 2014}}. Compelling epidemiologic evidence implicates hypovita- 56 minosis D as an important factor in the development of preeclampsia, 57 a form of gestational hypertension (Hypponen, 2005){{67 Roberts,J.M. 58 2003; 2228 Bodnar,L.M. 2014; 2242 Weinert,L.S. 2014}}. Placental insuf- 59 ficiency in early pregnancy precedes the acute consequences of pre- 60 eclampsia, a condition indicative of future risk for cardiovascular 61 disease and preeclampsia in offspring (Roberts and Hubel, 2010; 62 Anderson, 2007). Bodnar et al. found that low maternal vitamin D 63 prior to mid-gestation more than doubled the risk for subsequent devel- 64 opment of preeclampsia (Bodnar et al., 2007b). According to Haugen 65 et al., supplemental vitamin D during pregnancy reduced the risk for 66 preeclampsia by 27% (Haugen et al., 2009). Further, among women 67 who received vitamin D supplementation during their first year of life, Life Sciences xxx (2014) xxx–xxx ⁎ Corresponding author at: 1585 Neil Avenue, Newton 346, College of Nursing, The Ohio State University, Columbus, OH 43210, United States. Tel.: +1 614 292 4179; fax: +1 614 292 4948. E-mail address: anderson.2765@osu.edu (C.M. Anderson). LFS-14082; No of Pages 6 http://dx.doi.org/10.1016/j.lfs.2014.07.012 0024-3205/© 2014 Published by Elsevier Inc. Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie Please cite this article as: Anderson CM, et al, First trimester vitamin D status and placental epigenomics in preeclampsia among Northern Plains primiparas, Life Sci (2014), http://dx.doi.org/10.1016/j.lfs.2014.07.012