Abstract
BackgroundConcentrations 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.MethodsWe 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 β-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).ResultsThe 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.ConclusionsThe 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.
Highlights
MethodsAn HTR3A single nucleotide polymorphism (178 C/T) in the upstream regulatory region was recently discovered to be of putative functional importance, because luciferase reporter assays in human embryonal kidney cells showed a two to three times higher activity of the rare allele compared to the wildtype [14]
Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain
In the present study we have examined the HTR2C Cys23Ser, HTR3A 178 C/T, DRD4 521 C/T and DBH -1021 C/T variants for possible relationships to concentrations of 5-HIAA, homovanillic acid (HVA), and MHPG in lumbar CSF from healthy Swedish volunteers
Summary
An HTR3A single nucleotide polymorphism (178 C/T) in the upstream regulatory region was recently discovered to be of putative functional importance, because luciferase reporter assays in human embryonal kidney cells showed a two to three times higher activity of the rare allele compared to the wildtype [14]. This HTR3A variant was reported to be associated with bipolar disorder [14] and the personality trait harm avoidance in women [15]
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