Prenatal Arsenic Exposure and the Epigenome: Identifying Sites of 5-methylcytosine Alterations that Predict Functional Changes in Gene Expression in Newborn Cord Blood and Subsequent Birth Outcomes

• DOI: 10.1093/toxsci/kfu210
• Publication Date: 2014-10-11T03:33:37Z
• Authors: Daniel Rojas; Julia E. Rager; Lisa Smeester; Kathryn A. Bailey; Zuzana Drobná; Marisela Rubio-An...; Miroslav Stýblo; Gonzalo García-Va...; Rebecca C. Fry
• Keywords: CpG site; DNA binding site; Cord blood; Epigenomics

Prenatal exposure to inorganic arsenic (iAs) is detrimental the health of newborns and increases risk disease development later in life. Here we examined a subset newborn cord blood leukocyte samples collected from subjects enrolled Biomarkers Exposure ARsenic (BEAR) pregnancy cohort Gómez Palacio, Mexico, who were exposed range drinking water concentrations (0.456–236 µg/l). Changes iAs-associated DNA 5-methylcytosine methylation assessed across 424 935 CpG sites representing 18 761 genes compared with corresponding mRNA expression levels birth outcomes. In context exposure, total 2919 identified differences methylation. Site-specific analyses changes that most predictive gene where within islands positioned first exon, 5′ untranslated region 200 bp upstream transcription start site yielded significant association levels. A set 16 was correlated all highly enriched for binding early growth response (EGR) CCCTC-binding factor (CTCF) factors. Furthermore, 7 these associated outcomes including gestational age head circumference.These data highlight complex interplay between methylation, functional underscore need coupled epigenetic assessments.