title: NR4A2 and schizophrenia: lack of association in a Portuguese/Brazilian study.
abstract: The present study investigates the association of mutations in the nuclear receptor NR4A2 in schizophrenic patients. The human Nur-related receptor 1, NR4A2, is an orphan nuclear receptor that can be constitutively active as a transcription factor and for which no natural ligand has yet been identified. Alone or with retinoid X receptor, RXR, NR4A2 influences the expression of several genes important for human brain development and regulation. In the absence of Nurr1 (the mouse homologue to human NR4A2), ventral mesencephalic dopaminergic mouse neurons evidence severe developmental failure, a condition that is lethal soon after birth. Nurr1 involvement in the dopaminergic system makes it a good candidate for study in neuropsychiatric disorders such as schizophrenia and Parkinson disease. Evidence by others support this hypothesis (1) mapping of the NR4A2 gene to chromosome 2q22-23, a region with suggestive linkage to schizophrenia and (2) identification of mutations in patients with schizophrenia (c.366-369delTAC, c.308A > G, c.-469delG), manic depression (c.289A > G), and familial Parkinson's disease (c.-291delT, c.-245T > G). To further extend these observations, we searched for all these mutations in 176 Caucasian Portuguese and 82 Caucasian Brazilian subjects with lifetime diagnosis of schizophrenia. The study failed to identify any of the described mutations in patients or controls. Nevertheless, these negative results do not exclude altered expression of nuclear receptors in schizophrenia or the presence of other mutations.
authors.affiliation: Health Sciences School, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
authors.forename: Dina
authors.initials: D
authors.lastname: Ruano
authors.forename: António
authors.initials: A
authors.lastname: Macedo
authors.forename: Ana
authors.initials: A
authors.lastname: Dourado
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Soares
authors.forename: José
authors.initials: J
authors.lastname: Valente
authors.forename: Isabel
authors.initials: I
authors.lastname: Coelho
authors.forename: Vítor
authors.initials: V
authors.lastname: Santos
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Azevedo
authors.forename: Ann
authors.initials: A
authors.lastname: Goodman
authors.forename: Mara Helena
authors.initials: MH
authors.lastname: Hutz
authors.forename: Clarissa
authors.initials: C
authors.lastname: Gama
authors.forename: Maria Inês
authors.initials: MI
authors.lastname: Lobato
authors.forename: Paulo
authors.initials: P
authors.lastname: Belmonte-de-Abreu
authors.forename: Joana Almeida
authors.initials: JA
authors.lastname: Palha
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D011174:Portugal / Q000453:epidemiology; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C539882:NR4A2 protein, human; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014157:Transcription Factors