title: Tryptophan hydroxylase gene 1 (TPH1) variants associated with cerebrospinal fluid 5-hydroxyindole acetic acid and homovanillic acid concentrations in healthy volunteers.
abstract: Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. We investigated possible relationships between five TPH1 gene polymorphisms and cerebrospinal fluid (CSF) concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the major dopamine metabolite homovanillic acid (HVA), and the major norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n=132). The G-allele of the TPH1 rs4537731 (A-6526G) polymorphism was associated with 5-HIAA and HVA, but not MHPG concentrations. None of the other four TPH1 polymorphisms (rs211105, rs1800532, rs1799913 and rs7933505) were significantly associated with any of the monoamine metabolite concentrations. Two (rs4537731G/rs211105T/rs1800532C/rs1799913C/rs7933505G and rs4537731A/rs211105T/rs1800532C/rs1799913C/rs7933505G) of five common TPH1 five-allele haplotypes were associated with 5-HIAA and HVA concentrations in opposite directions. None of the common haplotypes was associated with MHPG concentrations in the CSF. The results suggest that TPH1 gene variation participates in the regulation of serotonin and dopamine turnover rates in the central nervous system of healthy human subjects.
authors.affiliation: Department of Clinical Neuroscience, HUBIN project, Karolinska Institutet and Hospital, R5:00, SE-171 76 Stockholm, Sweden.
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; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D007211:Indoles / Q000134:cerebrospinal fluid*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: D007211:Indoles; C026785:5-hydroxyindole; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase; D006719:Homovanillic Acid