Dystrobrevin-binding protein 1 gene (DTNBP1) variants associated with cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid concentrations in healthy volunteers |
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| Authors: | Dimitrios Andreou Peter Saetre Anna K Kähler Thomas Werge Ole A Andreassen Ingrid Agartz Göran C Sedvall Håkan Hall Lars Terenius Erik G Jönsson |
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| Institution: | aDepartment of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, R5:00, SE-171 76 Stockholm, Sweden;bDivision of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway;cDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264, USA;dDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet and Hospital, SE-171 76 Stockholm, Sweden;eResearch Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark;fTOP project, Division of Psychiatry, Ullevål University Hospital & Institute of Psychiatry, University of Oslo, Oslo, Norway;gDepartment of Psychiatry, Section Vinderen & Institute of Psychiatry, University of Oslo, NO-0317 Oslo, Norway;hDepartment of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden |
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| 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. |
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| Keywords: | Dystrobrevin-binding protein 1 gene (DTNBP1) Cerebrospinal fluid (CSF) 5-Hydroxyindoleacetic acid (5-HIAA) Homovanillic acid (HVA) 3-Methoxy-4-hydroxyphenylglycol (MHPG) |
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