title: Methylation matters: interaction between methylation density and serotonin transporter genotype predicts unresolved loss or trauma.
abstract: BACKGROUND
  Do genetic or epigenetic factors play a role in making some individuals more vulnerable than others to loss of attachment figures or other traumatic experiences?
  
  
  METHODS
  DNA was obtained from growth phase entrained Epstein-Barr Virus (EBV) transformed lymphoblast cell lines from 143 adopted participants. Genotype of the serotonin transporter linked polymorphic region (5HTTLPR) was determined, and methylation ratios for each of the C-phosphate-G (CpG) residues were assessed using quantitative mass spectroscopy. Unresolved loss or trauma was established using the Berkeley Adult Attachment Interview.
  
  
  RESULTS
  Higher levels of methylation of the 5HTT promoter associated CpG island were associated with increased risk of unresolved responses to loss or other trauma in carriers of the usually protective 5HTTLPR//variant. The ss variant of 5HTTLPR predicted more unresolved loss or trauma, but only in case of lower levels of methylation. Higher levels of methylation of the ss variant were associated with less unresolved loss or other trauma.
  
  
  CONCLUSIONS
  Associations between 5HTTLPR polymorphisms and psychological problems are significantly altered by environmentally induced methylation patterns. Methylation may serve as the interface between adverse environment and the developing organism.
authors.affiliation: Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands. vanijzen@fsw.leidenuniv.nl
authors.forename: Marinus H
authors.initials: MH
authors.lastname: van IJzendoorn
authors.forename: Kristin
authors.initials: K
authors.lastname: Caspers
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Bakermans-Kranenburg
authors.forename: Steven R H
authors.initials: SR
authors.lastname: Beach
authors.forename: Robert
authors.initials: R
authors.lastname: Philibert
mesh_terms: D000300:Adoption / Q000523:psychology; D002461:Cell Line, Transformed; D018899:CpG Islands / Q000502:physiology; D019175:DNA Methylation / Q000502:physiology; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D004854:Herpesvirus 4, Human; D006801:Humans; D007223:Infant; D007406:Interview, Psychological; D008297:Male; D011110:Polymorphism, Genetic / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000502:physiology; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins