title: D-amino acid oxidase activator gene (DAOA) variation affects cerebrospinal fluid homovanillic acid concentrations in healthy Caucasians.
abstract: The D-amino acid oxidase activator (DAOA) protein regulates the function of D-amino oxidase (DAO), an enzyme that catalyzes the oxidative deamination of D-3,4-dihydroxyphenylalanine (D-DOPA) and D-serine. D-DOPA is converted to L-3,4-DOPA, a precursor of dopamine, whereas D-serine participates in glutamatergic transmission. We hypothesized that DAOA polymorphisms are associated with dopamine, serotonin and noradrenaline turnover in the human brain. Four single-nucleotide polymorphisms, previously reported to be associated with schizophrenia, were genotyped. Cerebrospinal fluid (CSF) samples were drawn by lumbar puncture, and the 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) were measured. Two of the investigated polymorphisms, rs3918342 and rs1421292, were significantly associated with CSF HVA concentrations. Rs3918342 was found to be nominally associated with CSF 5-HIAA concentrations. None of the polymorphisms were significantly associated with MHPG concentrations. Our results indicate that DAOA gene variation affects dopamine turnover in healthy individuals, suggesting that disturbed dopamine turnover is a possible mechanism behind the observed associations between genetic variation in DAOA and behavioral phenotypes in humans.
authors.affiliation: Department of Clinical Neuroscience, HUBIN Project, Karolinska Institutet and Hospital, Stockholm, Sweden. dimitrios.andreou@sll.se
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Andreou
authors.forename: Peter
authors.initials: P
authors.lastname: Saetre
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: D000293:Adolescent; D000328:Adult; D003605:D-Amino-Acid Oxidase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People; D055815:Young Adult
chemical_list: D003605:D-Amino-Acid Oxidase; D006719:Homovanillic Acid