Abstract

In a study of iron deficiency of newborns in China, children who were iron deficient or not were evaluated behaviorally and with regard to brain structure and function, demonstrating the detrimental effects of pre-and postnatal iron deficiency. We also hypothesized that iron deficiency may be exacerbated by lead and pesticides exposure.Lead, iron and 20 different pesticides were assessed in cord blood/cord serum of 1000 infants born in rural Zhejiang province.Pilot Epigenome-wide analysis via the Infinium HumanMethylation450 BeadChip was performed on DNA from 36 neonates, selected from particularly high or low exposure samples. Comparing methylation at 422,108 CpG sites between exposure groups and controls, Pb was associated with the most differential methylation (7273 CpG sites at q<0.1) followed by iron deficiency (93 sites). Profenofos and vinclozolin were associated with methylation at <10 sites. Top concepts enriched among differentially methylated genes by lead involved sensory perception and taste, defense against bacterium, glutathione transferase activity, and retinol metabolism. Additional concepts were involved in immune response, oxygen and heme binding, lipoprotein particle remodeling, and peptidase/endopeptidase activities. Concepts enriched among the genes found to be differentially methylated by iron deficiency included taste transduction and sensory perception of bitter taste, lipoprotein particle receptor binding, ribosome assembly, immune response, and targets of three transcription factors (EVI1, IK1, and STAT5B).Our results suggest that lead dramatically changes DNA methylation patterns, while iron deficiency only has marginal effects. In this small sample, we saw no effect of cumulative presence (>5) of pesticides but the sample was too small to evaluate each pesticide individually. Diethyltoluamide was the most detected (67% of the sample).We will report on replication attempt in a larger study of 96 samples that is currently being analyzed.

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