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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
Brain
Dopamine
genetics
Female
Gene Frequency
Genotype
Homovanillic Acid
cerebrospinal fluid
metabolism
Humans
Hydroxyindoleacetic Acid
cerebrospinal fluid
metabolism
Longitudinal Studies
Male
Methoxyhydroxyphenylglycol
cerebrospinal fluid
metabolism
Middle Aged
Polymorphism
Genetic
Psychiatric Status Rating Scales
Receptor
Serotonin
5-HT2C
genetics
Receptors
Dopamine D2
genetics
Receptors
Dopamine D4
Receptors
Serotonin
5-HT3
genetics
Serotonin
metabolism
Variation (Genetics)

Bah Rösman, Jessica,1975Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för farmakologi,Institute of Physiology and Pharmacology, Dept of Pharmacology(Swepub:gu)xbahje (author)
Melke, Jonas,1971Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för farmakologi,Institute of Physiology and Pharmacology, Dept of Pharmacology(Swepub:gu)xmelkj (author)
Abou Jamra, Rami (author)
Schumacher, Johannes (author)
Westberg, Lars,1973Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för farmakologi,Institute of Physiology and Pharmacology, Dept of Pharmacology(Swepub:gu)xwelar (author)
Ivo, Roland (author)
Cichon, Sven (author)
Propping, Peter (author)
Nöthen, Markus M (author)
Eriksson, Elias,1956Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för farmakologi,Institute of Physiology and Pharmacology, Dept of Pharmacology(Swepub:gu)xereli (author)
Sedvall, Göran C (author)
Karolinska InstitutetInstitutionen för fysiologi och farmakologi, Avdelningen för farmakologi (creator_code:org_t)

By the author/editor: Jönsson, Erik G; Bah Rösman, Jess ...; Melke, Jonas, 19 ...; Abou Jamra, Rami; Schumacher, Joha ...; Westberg, Lars, ...; show more...; Ivo, Roland; Cichon, Sven; Propping, Peter; Nöthen, Markus M; Eriksson, Elias, ...; Sedvall, Göran C; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

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