Dopamine-related genes and their relationships to monoamine metabolites in CSF.
Monoamine metabolite (MM) levels in lumbar cerebrospinal fluid (CSF) are extensively used as indirect estimates of monoamine turnover in the brain. In this study we investigated genotypes for DNA polymorphisms in the D2 (DRD2), D3 (DRD3), and D4 (DRD4) dopamine receptor and tyrosine hydroxylase (TH) genes and their relationships to CSF MM in healthy volunteers (n = 66). Concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were corrected for back length, a confounding variable. Corrected MM levels were not related to age, gender, height, weight heredity, season or atmospheric pressure at sampling. Individuals with specific DRD2 and TH allele and genotype configurations significantly differed in HVA and MHPG concentrations. DRD3 homo- and heterozygotic genotypes had significantly different CSF 5-HIAA levels. DRD4 genotypes were not related to MM concentrations. The results suggest that specific DRD2, DRD3, and TH genotypes participate in the regulation of monoamine turnover in the central nervous system. Accordingly monoamine receptors and synthesizing enzyme genotypes appear to be variance factors influencing MM concentrations in CSF. The relationships found in this study support MM concentrations as markers for monoamine transmission in the human brain.
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
E
E
Jönsson
G
G
Sedvall
S
S
Brené
J P
JP
Gustavsson
T
T
Geijer
L
L
Terenius
M A
MA
Crocq
L
L
Lannfelt
A
A
Tylec
P
P
Sokoloff
J C
JC
Schwartz
F A
FA
Wiesel
D000328:Adult; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid* / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D004298:Dopamine / Q000235:genetics*; D005260:Female; D005838:Genotype; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D001523:Mental Disorders / Q000235:genetics; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011954:Receptors, Dopamine / Q000235:genetics*; D012621:Seasons; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D015306:Biogenic Monoamines; D011954:Receptors, Dopamine; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid