title: Systematic search for variations in the tyrosine hydroxylase gene and their associations with schizophrenia, affective disorders, and alcoholism.
abstract: Tyrosine hydroxylase is the rate-limiting step in the biosynthesis of catecholamines. To find variants in the tyrosine hydroxylase (TH) gene that are associated with schizophrenia, mood disorders, or alcohol dependence, all of the exons, the exon-intron boundaries, and the 5' promoter region of the TH gene were systematically screened for variants by single-strand conformation polymorphism analysis followed by direct nucleotide sequencing. Source DNAs for sequencing were from 88 Japanese patients comprised of 17 schizophrenics, 21 with mood disorders, and 50 alcoholics. Two novel variants, T-229A and Val468Met, were identified. Case-control comparisons demonstrated that distribution of these two variants were similar in the controls and the three psychiatric groups. Distributions of the previously reported Val81Met polymorphism alleles and the intron 1 TCAT repeat polymorphism alleles were similar in the four subject groups. Our study indicates that the TH gene is not likely to play a major role in the genetic predisposition to schizophrenia, mood disorders, or alcohol dependence.
authors.affiliation: Department of Neuropsychiatry, Tokyo Medical and Dental University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishiguro
authors.forename: T
authors.initials: T
authors.lastname: Arinami
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Akazawa
authors.forename: M
authors.initials: M
authors.lastname: Enomoto
authors.forename: H
authors.initials: H
authors.lastname: Mitushio
authors.forename: H
authors.initials: H
authors.lastname: Fujishiro
authors.forename: K
authors.initials: K
authors.lastname: Tada
authors.forename: Y
authors.initials: Y
authors.lastname: Akimoto
authors.forename: H
authors.initials: H
authors.lastname: Mifune
authors.forename: S
authors.initials: S
authors.lastname: Shiozuka
authors.forename: H
authors.initials: H
authors.lastname: Hamaguchi
authors.forename: M
authors.initials: M
authors.lastname: Toru
authors.forename: H
authors.initials: H
authors.lastname: Shibuya
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000235:genetics*; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019964:Mood Disorders / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D014446:Tyrosine 3-Monooxygenase