title: Functional polymorphism (C-824T) of the tyrosine hydroxylase gene affects IQ in schizophrenia.
abstract: OBJECTIVE
  Progressive cognitive decline has been an important issue in the treatment and care of patients with schizophrenia. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the biosynthesis of catecholamine, including dopamine and noradrenaline. In this report, we examined a possible association of a genetic variant in the TH promoter region.
  
  
  METHODS
  Association of a genetic variant in the TH promoter region, C-824T (rs10770141), with intellectual ability in 132 patients with schizophrenia and 282 healthy subjects was examined. The transcriptional activity of the plasmids harboring the TH promoter region with either C or T nucleotide at -824 was assayed using a luciferase gene as a reporter.
  
  
  RESULTS
  We found significant effects of the genotype on the full-scale IQ, verbal IQ, and performance IQ, in patients with schizophrenia. IQ was lower in individuals with the C/C genotype than those with T carriers. The plasmid with the T allele at -824 showed higher transcriptional activity than that with the C allele in a transient transfection experiment using a luciferase gene as a reporter, implying that the T carriers may have higher TH activities and retain higher levels of catecholamines in the brain.
  
  
  CONCLUSIONS
  The present data suggest that the biosynthesis of catecholamine by the action of TH should be deeply involved in decreased intellectual ability in patients with schizophrenia. This is the first report, as far as we know, showing a correlation between TH expression and IQ in humans.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama.
authors.forename: Mieko
authors.initials: M
authors.lastname: Horiguchi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohi
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Qinyu
authors.initials: Q
authors.lastname: Hao
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.forename: Michiko
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Satomi
authors.initials: S
authors.lastname: Umeda-Yano
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichinose
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D005838:Genotype; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D007361:Intelligence Tests; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
chemical_list: D014446:Tyrosine 3-Monooxygenase
keywords: IQ; TH gene polymorphism; Tyrosine hydroxylase; Wechsler Adult Intelligence Scale-III; schizophrenia