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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Keyword

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)

Publication and Content Type

ref (subject category)

art (subject category)