title: Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers.
abstract: BACKGROUND
  Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences.
  
  
  METHODS
  We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C), the serotonin 3A receptor (HTR3A), the dopamine D4 receptor (DRD4), and the dopamine beta-hydroxylase (DBH) genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 90).
  
  
  RESULTS
  The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02). The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005) and HVA (p = 0.009) concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites.
  
  
  CONCLUSIONS
  The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system.
authors.affiliation: Department of Clinical Neuroscience, Psychiatry Section, HUBIN project, Karolinska Institutet, Stockholm, Sweden. erikj@ks.se
authors.forename: Erik G
authors.initials: EG
authors.lastname: Jönsson
authors.forename: Jessica
authors.initials: J
authors.lastname: Bah
authors.forename: Jonas
authors.initials: J
authors.lastname: Melke
authors.forename: Rami
authors.initials: R
authors.lastname: Abou Jamra
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
authors.forename: Lars
authors.initials: L
authors.lastname: Westberg
authors.forename: Roland
authors.initials: R
authors.lastname: Ivo
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
authors.forename: Göran C
authors.initials: GC
authors.lastname: Sedvall
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid* / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics; D012701:Serotonin / Q000378:metabolism*
chemical_list: C493599:DRD4 protein, human; D044405:Receptor, Serotonin, 5-HT2C; D017448:Receptors, Dopamine D2; D044406:Receptors, Serotonin, 5-HT3; D050638:Receptors, Dopamine D4; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine; D006719:Homovanillic Acid