Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers.
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.
Jönsson
Erik G
EG
Department of Clinical Neuroscience, Psychiatry Section, HUBIN project, Karolinska Institutet, Stockholm, Sweden. erikj@ks.se
Bah
Jessica
J
Melke
Jonas
J
Abou Jamra
Rami
R
Schumacher
Johannes
J
Westberg
Lars
L
Ivo
Roland
R
Cichon
Sven
S
Propping
Peter
P
Nöthen
Markus M
MM
Eriksson
Elias
E
Sedvall
Göran C
GC
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*
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