Dystrobrevin-binding protein 1 gene (DTNBP1) variants associated with cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid concentrations in healthy volunteers

Eur Neuropsychopharmacol. 2011 Sep;21(9):700-4. doi: 10.1016/j.euroneuro.2010.12.008. Epub 2011 Feb 4.

Abstract

The dystrobrevin binding protein-1 (DTNBP1) gene encodes dysbindin-1, a protein involved in neurodevelopmental and neurochemical processes related mainly to the monoamine dopamine. We investigated possible associations between eleven DTNBP1 polymorphisms and cerebrospinal fluid (CSF) concentrations of the major dopamine metabolite homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and the major noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy human subjects (n=132). Two polymorphisms, rs2619538 and rs760666, were nominally associated with CSF HVA and 5-HIAA concentrations, whereas a third polymorphism, rs909706, showed association only with HVA. After correction for multiple testing only the associations between rs2619538 and HVA and 5-HIAA concentrations remained significant. No significant association was found between any of the investigated DTNBP1 polymorphisms and CSF MHPG concentrations. The results suggest that genetic variation in DTNBP1 gene affects the regulation of dopamine and serotonin turnover in the central nervous system of healthy volunteers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Dopamine / metabolism
  • Dysbindin
  • Dystrophin-Associated Proteins
  • Female
  • Gene Frequency
  • Genetic Variation
  • Genotype
  • Homovanillic Acid / cerebrospinal fluid*
  • Homovanillic Acid / metabolism
  • Humans
  • Hydroxyindoleacetic Acid / cerebrospinal fluid*
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Methoxyhydroxyphenylglycol / cerebrospinal fluid*
  • Methoxyhydroxyphenylglycol / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neurotransmitter Agents / metabolism*
  • Norepinephrine / metabolism
  • Polymorphism, Single Nucleotide
  • Serotonin / metabolism

Substances

  • BLOC1S1 protein, human
  • Carrier Proteins
  • DTNBP1 protein, human
  • Dysbindin
  • Dystrophin-Associated Proteins
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Serotonin
  • Methoxyhydroxyphenylglycol
  • Hydroxyindoleacetic Acid
  • Dopamine
  • Norepinephrine
  • Homovanillic Acid