Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers

Jönsson, Erik G.; Bah, Jessica; Melke, Jonas; Jamra, Rami Abou; Schumacher, Johannes; Westberg, Lars; Ivo, Roland; Cichon, Sven; Propping, Peter; Nöthen, Markus M.; Eriksson, Elias; Sedvall, Göran C.
January 2004
BMC Psychiatry;2004, Vol. 4, p4
Academic Journal
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 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). 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.


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