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Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia
Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Department of Chemistry and Biomedical Sciences, Faculty of Health and Life Sciences, Linnaeus University, Kalmar, Sweden. (Exprimentel Neuropsykiatri)
Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Örebro University, School of Health Sciences. Department of Clinical Medicine. (Exprimentel Neuropsykiatri)
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2017 (English)In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 74, no 2, 96-103 p.Article in journal (Refereed) Published
Abstract [en]

Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.

Place, publisher, year, edition, pages
Basel: S. Karger, 2017. Vol. 74, no 2, 96-103 p.
Keyword [en]
Amino acid transporter light chain system L; Fibroblasts; L-Type amino acid transporter 1; Schizophrenia; Single-nucleotide polymorphism; Tyrosine
National Category
Psychiatry Psychology Neurology
Research subject
Psychiatry; Genetics; Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-55674DOI: 10.1159/000455234ISI: 000399488600008PubMedID: 28190014Scopus ID: 2-s2.0-85013072462OAI: oai:DiVA.org:oru-55674DiVA: diva2:1074028
Available from: 2017-02-14 Created: 2017-02-14 Last updated: 2017-05-16Bibliographically approved

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