title: Transthyretin: no association between serum levels or gene variants and schizophrenia.
abstract: It has been proposed that schizophrenia results from an environmental insult in genetically predisposed individuals. Environmental factors capable of modulating transcriptional activity and their carriers could link the genetic and environmental components of schizophrenia. Among these is transthyretin (TTR), a major carrier of thyroid hormones and retinol-binding protein (RBP). Retinoids and thyroid hormones regulate the expression of several genes, both during development and in the adult brain. Decreased TTR levels have been reported in the cerebrospinal fluid of patients with depression and Alzheimer's disease, and the absence of TTR influences behavior in mice. DNA variants capable of altering TTR ability to carry its ligands, either due to reduced transcription of the gene or to structural modifications of the protein, may influence development of the central nervous system and behavior. In the present study we searched for variants in the regulatory and coding regions of the TTR gene, and measured circulating levels of TTR and RBP. We found a novel single nucleotide polymorphism (SNP), ss46566417, 18 bp upstream of exon 4. Neither this SNP nor the previously described rs1800458 were found associated with schizophrenia. In addition, serum TTR and RBP levels did not differ between mentally healthy and schizophrenic individuals. In conclusion, our data does not support an involvement of the TTR gene in the pathophysiology of schizophrenia.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, 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: Maria J
authors.initials: MJ
authors.lastname: Soares
authors.forename: José
authors.initials: J
authors.lastname: Valente
authors.forename: Maria H
authors.initials: MH
authors.lastname: Azevedo
authors.forename: Mara H
authors.initials: MH
authors.lastname: Hutz
authors.forename: Clarissa S
authors.initials: CS
authors.lastname: Gama
authors.forename: Maria I
authors.initials: MI
authors.lastname: Lobato
authors.forename: Paulo
authors.initials: P
authors.lastname: Belmonte-de-Abreu
authors.forename: Ann B
authors.initials: AB
authors.lastname: Goodman
authors.forename: Carlos
authors.initials: C
authors.lastname: Pato
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Saraiva
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
authors.forename: Joana A
authors.initials: JA
authors.lastname: Palha
mesh_terms: D000328:Adult; D001938:Brazil; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011174:Portugal; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism*; D012016:Reference Values; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D012559:Schizophrenia / Q000097:blood* / Q000235:genetics*; D012931:Social Environment; D013223:Statistics as Topic
chemical_list: D011228:Prealbumin; D012177:Retinol-Binding Proteins