title: Placental DNA methylation alterations associated with maternal tobacco smoking at the RUNX3 gene are also associated with gestational age.
abstract: OBJECTIVE
  The developmental origins of health and disease hypothesis states that later-life disease may be influenced by the quality of the in utero environment. Environmental toxicants can have detrimental effects on fetal development, potentially through effects on placental development and function. Maternal smoking during pregnancy is associated with low birth weight, preterm birth and other complications, and exposure to cigarette smoke in utero has been linked to gross pathologic and molecular changes to the placenta, including differential DNA methylation in placental tissue. The aim of this study was to investigate the relationship between maternal smoking during pregnancy, methylation changes in the placenta and gestational age.
  
  
  METHODS
  We used Illumina(®)'s (CA, USA) Human Methylation27 BeadChip technology platform to investigate the methylation status of 21,551 autosomal, non-SNP-associated CpG loci in DNA extracted from 206 human placentas and examined loci whose variation in methylation was associated with maternal smoking during pregnancy.
  
  
  RESULTS
  We found that methylation patterns of a number of loci within the RUNX3 gene were significantly associated with smoking during pregnancy, and one of these loci was associated with decreased gestational age (p = 0.04).
  
  
  CONCLUSIONS
  Our findings, demonstrating maternal smoking-induced changes in DNA methylation at specific loci, suggest a mechanism by which in utero tobacco smoke exposure could exert its detrimental effects upon the health of the fetus.
authors.affiliation: Department of Pathology & Laboratory Medicine, Brown University, Providence, RI, USA.
authors.forename: Jennifer Z J
authors.initials: JZ
authors.lastname: Maccani
authors.forename: Devin C
authors.initials: DC
authors.lastname: Koestler
authors.forename: Eugene Andrés
authors.initials: EA
authors.lastname: Houseman
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
mesh_terms: D000328:Adult; D001724:Birth Weight / Q000235:genetics; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D008040:Genetic Linkage; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D012907:Smoking / Q000235:genetics*; D055815:Young Adult
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human