MAOA methylation is associated with nicotine and alcohol dependence in women

Am J Med Genet B Neuropsychiatr Genet. 2008 Jul 5;147B(5):565-70. doi: 10.1002/ajmg.b.30778.


In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus. In order to examine the role of methylation at this locus, we performed quantitative methylation analysis across the promoter region of this gene in lymphoblast lines derived from 191 subjects participating in the Iowa Adoption Studies (IAS). We analyzed the resulting data with respect to genotype and lifetime symptom counts for the more common major behavioral disorders in the IAS, antisocial personality disorder (ASPD), and substance use disorders (alcohol (AD) and nicotine dependence (ND)). We found that methylation status was significantly associated with lifetime symptom counts for ND (P < 0.001) and AD (P < 0.008) in women, but not men. Furthermore, a trend was found for women homozygous for the 3,3 allele to have a higher degree of overall methylation than women homozygous for the 4,4 allele (P < 0.10). We conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alcoholism / enzymology*
  • Alcoholism / genetics
  • Antisocial Personality Disorder / enzymology
  • Antisocial Personality Disorder / genetics
  • Base Sequence
  • Case-Control Studies
  • Cell Line, Transformed
  • DNA Methylation*
  • Female
  • Humans
  • Lymphocytes / enzymology
  • Male
  • Molecular Sequence Data
  • Monoamine Oxidase / genetics
  • Monoamine Oxidase / metabolism*
  • Nicotine / adverse effects*
  • Pilot Projects
  • Promoter Regions, Genetic
  • Sex Factors


  • Nicotine
  • Monoamine Oxidase