title: Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and monoamine metabolite concentrations in cerebrospinal fluid.
abstract: Angiotensin II has been suggested to influence central dopamine and serotonin turnover. Since the angiotensin-converting enzyme (ACE) plays a key role in angiotensin regulation by converting inactive angiotensin I to active angiotensin II, we hypothesised that the functional insertion/deletion (I/D) polymorphism in the ACE gene, which has previously been suggested to be associated with, depression and panic disorder, may influence monoamine activity. A well-established technique for assessing brain monoamine turnover in humans is to measure concentrations of monoamine metabolites in the cerebrospinal fluid (CSF). We thus investigated possible associations between the ACE I/D polymorphism and CSF monoamine metabolite concentrations in a population of healthy male subjects. After having found such an association between the ACE I/D polymorphism and CSF levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid in this sample, I carriers displaying lower levels, we tried to replicate this observation in a population of violent male offenders from which also both CSF and DNA were available. Also in this sample, the same associations were found. Our results suggest that the ACE I/D polymorphism may play a role in the modulation of serotonergic and dopaminergic turnover in men.
authors.affiliation: Department of Pharmacology, University of Gothenburg, S-405 30, Gothenburg, Sweden. kristina.annerbrink@pharm.gu.se
authors.forename: Kristina
authors.initials: K
authors.lastname: Annerbrink
authors.forename: Erik G
authors.initials: EG
authors.lastname: Jönsson
authors.forename: Marie
authors.initials: M
authors.lastname: Olsson
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Göran C
authors.initials: GC
authors.lastname: Sedvall
authors.forename: Henrik
authors.initials: H
authors.lastname: Anckarsäter
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
mesh_terms: D000293:Adolescent; D000328:Adult; D057237:Criminals; D055106:Genome-Wide Association Study; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid*; D016254:Mutagenesis, Insertional / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D007703:Peptidyl-Dipeptidase A; D006719:Homovanillic Acid