Abstract
Dystrobrevin binding protein 1 (DTNBP1) gene is pivotal in regulating the glutamatergic system. Genetic variants of the DTNBP1 affect cognition and thus may be particularly relevant to schizophrenia. We therefore evaluated the association of six single nucleotide polymorphisms (SNPs) with schizophrenia in a Malaysian population (171 cases; 171 controls). Associations between these six SNPs and schizophrenia were tested in two stages. Association signals with p < 0.05 and minor allele frequency > 0.05 in stage 1 were followed by genotyping the SNPs in a replication phase (stage 2). Genotyping was performed with sequenced specific primer (PCR-SSP) and restriction fragment length polymorphism (PCR-RFLP). In our sample, we found significant associations between rs2619522 (allele p = 0.002, OR = 1.902, 95%CI = 1.266 – 2.859; genotype p = 0.002) and rs2619528 (allele p = 0.008, OR = 1.606, 95%CI = 1.130 – 2.281; genotype p = 6.18 × 10−5) and schizophrenia. Given that these two SNPs may be associated with the pathophysiology of schizophrenia, further studies on the other DTNBP1 variants are warranted.
Highlights
The dystrobrevin binding protein 1 (DTNBP1) gene, known as dysbindin gene, is located at 6p22.3, a highly susceptible gene region of schizophrenia (Moises et al, 1995; Straub et al, 2002)
DTNBP1 mRNA is predominantly expressed in the dorsolateral prefrontal cortex (DLPFC) and hippocampus (Weickert et al, 2004; Tang et al, 2009)
Mini International Neuropsychiatric Interview (MINI) has been validated by senior psychiatrists and compared against Structured Clinical Interview for DSM-III-R (SCID) and Composite In-ternational Diagnostic Interview (CIDI) (Sheehan et al, 1998)
Summary
The dystrobrevin binding protein 1 (DTNBP1) gene, known as dysbindin gene, is located at 6p22.3, a highly susceptible gene region of schizophrenia (Moises et al, 1995; Straub et al, 2002) It spans 140 kb along the chromosome and has 10 exons (Guo et al, 2009). Reduced DTNBP1 expression (Talbot et al, 2004; Weickert et al, 2004, 2008; Tang et al, 2009) was reported in schizophrenia patients This reduction was inversely correlated with an increase of vesicular glutamate transporter 1 (VGluT-1) as a result of reduced lysosomal trafficking (Owen et al, 2004; Talbot et al, 2004).
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