title: Changes in the methylation status of DAT, SERT, and MeCP2 gene promoters in the blood cell in families exposed to alcohol during the periconceptional period.
abstract: BACKGROUND
  Alcohol exposure has been shown to cause devastating effects on neurobehavioral development in numerous animal and human studies. The alteration of DNA methylation levels in gene-specific promoter regions has been investigated in some studies of human alcoholics. This study was aimed to investigate whether social alcohol consumption during periconceptional period is associated with epigenetic alteration and its generational transmission in the blood cells.
  
  
  METHODS
  We investigated patterns of alcohol intake in a prospective cohort of 355 pairs of pregnant women and their spouses who reported alcohol intake during the periconceptional period. A subpopulation of 164 families was established for the epigenetic study based on the availability of peripheral blood and cord blood DNA. The relative methylation changes of dopamine transporter (DAT), serotonin transporter (SERT), and methyl CpG binding protein 2 (MeCP2) gene promoters were analyzed using methylation-specific endonuclease digestion followed by quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  The relative methylation level of the DAT gene promoter was decreased in the group of mothers reporting above moderate drinking (p = 0.029) and binge drinking (p = 0.037) during pregnancy. The relative methylation level of the DAT promoter was decreased in the group of fathers reporting heavy binge drinking (p = 0.003). The relative methylation levels of the SERT gene promoter were decreased in the group of newborns of light drinking mothers before pregnancy (p = 0.012) and during pregnancy (p = 0.003). The methylation level in the MeCP2 promoter region of babies whose mothers reported above moderate drinking during pregnancy was increased (p = 0.02). In addition, methylation pattern in the DAT promoter region of babies whose fathers reported heavy binge drinking was decreased (p = 0.049).
  
  
  CONCLUSIONS
  These findings suggest that periconceptional alcohol intake may cause epigenetic changes in specific locus of parental and newborn genomes as follows: Alcohol consumption decreases the methylation level of the DAT promoter region of the parent themselves, maternal alcohol drinking during the periconceptional period decreases the methylation level of the SERT promoter region of newborns, and maternal alcohol consumption increases the methylation level of the MeCP2 promoter region of newborns.
authors: Laboratory of Medical Genetics, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea; Department of Medical Genetics, College of Medicine, Hanyang University, Seoul, Korea.
authors: Bom-Yi
authors: BY
authors: Lee
authors: So-Yeon
authors: SY
authors: Park
authors: Hyun-Mee
authors: HM
authors: Ryu
authors: Chan-Young
authors: CY
authors: Shin
authors: Ki-Nam
authors: KN
authors: Ko
authors: Jung-Yeol
authors: JY
authors: Han
authors: Gideon
authors: G
authors: Koren
authors: Youl-Hee
authors: YH
authors: Cho
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism*; D063425:Binge Drinking / Q000378:metabolism*; D015331:Cohort Studies; D019175:DNA Methylation; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic; D005220:Fathers; D005260:Female; D005306:Fertilization; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009035:Mothers; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: Alcohol; Dopamine Transporter; Gene Promoter Methylation; Methyl CpG Binding Protein 2; Serotonin Transporter