title: Differential DNA methylation in umbilical cord blood of infants exposed to low levels of arsenic in utero.
abstract: BACKGROUND
  There is increasing epidemiologic evidence that arsenic exposure in utero, even at low levels found throughout much of the world, is associated with adverse reproductive outcomes and may contribute to long-term health effects. Animal models, in vitro studies, and human cancer data suggest that arsenic may induce epigenetic alterations, specifically by altering patterns of DNA methylation.
  
  
  OBJECTIVE
  In this study we aimed to identify differences in DNA methylation in cord blood samples of infants with in utero, low-level arsenic exposure.
  
  
  METHODS
  DNA methylation of cord-blood derived DNA from 134 infants involved in a prospective birth cohort in New Hampshire was profiled using the Illumina Infinium Methylation450K array. In utero arsenic exposure was estimated using maternal urine samples collected at 24-28 weeks gestation. We used a novel cell mixture deconvolution methodology for examining the association between inferred white blood cell mixtures in infant cord blood and in utero arsenic exposure; we also examined the association between methylation at individual CpG loci and arsenic exposure levels.
  
  
  RESULTS
  We found an association between urinary inorganic arsenic concentration and the estimated proportion of CD8+ T lymphocytes (1.18; 95% CI: 0.12, 2.23). Among the top 100 CpG loci with the lowest p-values based on their association with urinary arsenic levels, there was a statistically significant enrichment of these loci in CpG islands (p = 0.009). Of those in CpG islands (n = 44), most (75%) exhibited higher methylation levels in the highest exposed group compared with the lowest exposed group. Also, several CpG loci exhibited a linear dose-dependent relationship between methylation and arsenic exposure.
  
  
  CONCLUSIONS
  Our findings suggest that in utero exposure to low levels of arsenic may affect the epigenome. Long-term follow-up is planned to determine whether the observed changes are associated with health outcomes.
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA.
authors.forename: Devin C
authors.initials: DC
authors.lastname: Koestler
authors.forename: Michele
authors.initials: M
authors.lastname: Avissar-Whiting
authors.forename: E Andres
authors.initials: EA
authors.lastname: Houseman
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
mesh_terms: D000328:Adult; D001151:Arsenic / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D018899:CpG Islands / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D013058:Mass Spectrometry; D018811:Maternal Exposure; D009513:New Hampshire / Q000453:epidemiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology* / Q000235:genetics; D011446:Prospective Studies; D014874:Water Pollutants, Chemical / Q000652:urine*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014874:Water Pollutants, Chemical; D001151:Arsenic