SNAT1 and a family with high rates of suicidal behavior

• Published in: Neuroscience Vol. 162; no. 2; pp. 415 - 422
• Main Authors: Ernst, C, Dumoulin, P, Cabot, S, Erickson, J, Turecki, G
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 18.08.2009; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Amino Acid Transport System A - biosynthesis; Amino Acid Transport System A - genetics; Biological and medical sciences; Brain - metabolism; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; glutamate metabolism; Humans; Male; Medical sciences; Middle Aged; neurogenetics; Neurology; Oligonucleotide Array Sequence Analysis; Pedigree; Polymorphism, Single Nucleotide; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; SNAT1; Suicide; Suicide - psychology; Vertebrates: nervous system and sense organs; TBS; Sodium-coupled neutral amino acid transporter 1; suicide; neurogenetics; motor vehicle accident; quantitative polymerase chain reaction; cardiac arrest; EVA; Tris-buffered saline; SNAT1; extreme values analysis; PAINT; MVA; glutamate metabolism; qPCR; CA; promoter analysis and interaction network generation tool; Excitatory aminoacid; Neurotransmitter; Behavior; Glutamate; Metabolism; Suicide
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.05.010

Abstract Several lines of evidence suggest that suicide may have, in part, a genetic predisposition. In this study, we identified a family with high rates of suicidal behavior and assessed brain gene expression levels in the proband. A neuronally-expressed solute carrier for glutamine (Sodium-coupled neutral amino acid transporter 1 (SNAT1), also known as solute carrier family 38, member 1 (SLC38A1)) was identified as severely decreased across all brain regions. Follow-up analysis by semi-quantitative polymerase chain reaction (qPCR) and Western blot confirmed the reduction of SNAT1. We categorized the SNAT1 gene in human brain, cloned the gene promoter and assessed in silico the expression pattern of SNAT1 in >25 tissues from human. Complete DNA sequencing of the SNAT1 gene was performed in the family and 276 controls. The family was homozygous for rare alleles which suggests a possible association between low expression of SNAT1 and suicidal behavior.