Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers.
Concentrations of monoamine metabolites (MM) in lumbar cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. We investigated the possible relationships between DNA polymorphisms in the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) genes and CSF concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 66). The DAT polymorphism was not significantly associated with any of the monoamine metabolites, but a tendency for relationship with 5-HIAA was found in women. For both of the two SERT polymorphisms investigated, a functional promoter polymorphism and an intronic polymorphism without known function, significant relationships were found with CSF MHPG levels. No relationship was found between the SERT polymorphisms and CSF HVA and 5-HIAA. The NET polymorphism was associated with CSF MHPG levels but not HVA and 5-HIAA concentrations. The results suggest that SERT and NET genotypes may participate differentially in the regulation of the norepinephrine turnover rate under presumed steady-state conditions in the central nervous system. As only limited data so far indicate interactions between the serotonin and norepinephrine systems in the brain, and the NET polymorphism investigated is not known to be of functional significance, the results should be interpreted with caution until replicated.
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. erikj@psyk.ks.se
E G
EG
Jönsson
M M
MM
Nöthen
J P
JP
Gustavsson
H
H
Neidt
R
R
Bunzel
P
P
Propping
G C
GC
Sedvall
D000328:Adult; D000704:Analysis of Variance; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D005838:Genotype; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D012737:Sex Factors; D027981:Symporters
D015306:Biogenic Monoamines; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid