title: DNA methylation patterns in newborns exposed to tobacco in utero.
abstract: BACKGROUND
  Maternal smoking during pregnancy is a major risk factor for adverse health outcomes. The main objective of the study was to assess the impact of in utero tobacco exposure on DNA methylation in children born at term with appropriate weight at birth.
  
  
  METHODS
  Twenty mother-newborn dyads, after uncomplicated pregnancies, in the absence of perinatal illness were included. All mothers were healthy with no cardiovascular risk factors, except for the associated risks among those mothers who smoked. Umbilical cord blood and maternal peripheral venous blood were collected and an epigenome-wide association study was performed using a 450 K epigenome-wide scan (Illumina Infinium HumanMethylation 450BeadChip) with adjustment to normalize the DNA methylation for data cell variability in whole blood.
  
  
  RESULTS
  The maternal plasmatic cotinine levels ranged from 10.70-115.40 ng/ml in the exposed group to 0-0.59 ng/ml in the non-exposed group. After adjusting for multiple comparisons in 427102 probes, statistically significant differences for 31 CpG sites, associated to 25 genes were observed. There was a greater than expected proportion of statistically-significant loci located in CpG islands (Fisher's exact test, p = 0.029) and of those CpG islands, 90.3% exhibit higher methylation levels in the exposed group. The most striking and significant CpG site, cg05727225, is located in the chromosome 11p15.4, within the adrenomedullin gene.
  
  
  CONCLUSIONS
  In utero tobacco exposure, even in the absence of fetal growth restriction, may alter the epigenome, contributing to global DNA hypomethylation. Therefore, DNA status can be used as a biomarker of prenatal insults. Considering the possibility to reverse epigenetic modifications, a window of opportunity exists to change the programmed chronic disease.
authors.affiliation: Pediatrics Department, Consorcio Hospital General, University of Valencia, Valencia, Spain. Carmen.Ivorra@uv.es.|CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Madrid, Spain. Carmen.Ivorra@uv.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ivorra
authors.affiliation: IUOPA Cancer Epigenetics Laboratory, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CNB-CSIC, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain. mffraga@cnb.csic.es.
authors.forename: Mario F
authors.initials: MF
authors.lastname: Fraga
authors.affiliation: IUOPA Cancer Epigenetics Laboratory, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CNB-CSIC, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain. fernandezgustavo@uniovi.es.
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Bayón
authors.affiliation: IUOPA Cancer Epigenetics Laboratory, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CNB-CSIC, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain. affernandez@hca.es.
authors.forename: Agustín F
authors.initials: AF
authors.lastname: Fernández
authors.affiliation: Pediatrics Department, Consorcio Hospital General, University of Valencia, Valencia, Spain. jec_jec_@hotmail.com.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Garcia-Vicent
authors.affiliation: Hospital Clínico de Valencia-INCLIVA Valencia, University of Valencia, Valencia, Spain. felipe.chaves@uv.es.|CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. felipe.chaves@uv.es.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Chaves
authors.affiliation: CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Madrid, Spain. josep.redon@uv.es.|Hospital Clínico de Valencia-INCLIVA Valencia, University of Valencia, Valencia, Spain. josep.redon@uv.es.
authors.forename: Josep
authors.initials: J
authors.lastname: Redon
authors.affiliation: Pediatrics Department, Consorcio Hospital General, University of Valencia, Valencia, Spain. empar.lurbe@uv.es.|CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Madrid, Spain. empar.lurbe@uv.es.
authors.forename: Empar
authors.initials: E
authors.lastname: Lurbe
mesh_terms: D053607:Adrenomedullin / Q000737:chemistry; D000328:Adult; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005260:Female; D005312:Fetal Blood; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D007118:Immunoassay; D007231:Infant, Newborn; D018811:Maternal Exposure; D009035:Mothers; D011247:Pregnancy; D012307:Risk Factors; D014028:Tobacco Smoke Pollution; D055815:Young Adult; D014026:Nicotiana
chemical_list: D014028:Tobacco Smoke Pollution; D053607:Adrenomedullin