title: Dystrobrevin-binding protein 1 gene (DTNBP1) variants associated with cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid concentrations in healthy volunteers.
abstract: The dystrobrevin binding protein-1 (DTNBP1) gene encodes dysbindin-1, a protein involved in neurodevelopmental and neurochemical processes related mainly to the monoamine dopamine. We investigated possible associations between eleven DTNBP1 polymorphisms and cerebrospinal fluid (CSF) concentrations of the major dopamine metabolite homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and the major noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy human subjects (n=132). Two polymorphisms, rs2619538 and rs760666, were nominally associated with CSF HVA and 5-HIAA concentrations, whereas a third polymorphism, rs909706, showed association only with HVA. After correction for multiple testing only the associations between rs2619538 and HVA and 5-HIAA concentrations remained significant. No significant association was found between any of the investigated DTNBP1 polymorphisms and CSF MHPG concentrations. The results suggest that genetic variation in DTNBP1 gene affects the regulation of dopamine and serotonin turnover in the central nervous system of healthy volunteers.
authors.affiliation: Department of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, R5:00, SE-17176 Stockholm, Sweden.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Andreou
authors.forename: Peter
authors.initials: P
authors.lastname: Saetre
authors.forename: Anna K
authors.initials: AK
authors.lastname: Kähler
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
authors.forename: Göran C
authors.initials: GC
authors.lastname: Sedvall
authors.forename: Håkan
authors.initials: H
authors.lastname: Hall
authors.forename: Lars
authors.initials: L
authors.lastname: Terenius
authors.forename: Erik G
authors.initials: EG
authors.lastname: Jönsson
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid* / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012701:Serotonin / Q000378:metabolism
chemical_list: C104378:BLOC1S1 protein, human; D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid