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 f luid (CSF) have been used extensively as indirect estimates of monoami ne turnover in the brain. We investigated the possible relationships b etween 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 volun teers (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 polymorphism s investigated, a functional promoter polymorphism and an intronic pol ymorphism without known function, significant relationships were found with CSF MHPG levels. No relationship was found between the SERT poly morphisms and CSF HVA and 5-HIAA. The NET polymorphism was associated with CSF MHPG levels but not HVA and 5-HIAA concentrations. The result s suggest that SERT and NET genotypes may participate differentially i n the regulation of the norepinephrine turnover rate under presumed st eady-state conditions in the central nervous system. As only limited d ata so far indicate interactions between the serotonin and norepinephr ine systems in the brain, and the NET polymorphism investigated is not known to be of functional significance, the results should be interpr eted with caution until replicated. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.