Abstract
The SAP97 gene is located in the schizophrenia susceptibility locus 3q29, and it encodes the synaptic scaffolding protein that interacts with the N-methyl-D-aspartate (NMDA) receptor, which is presumed to be dysregulated in schizophrenia. In this study, we genotyped a single-nucleotide polymorphism (SNP) (rs3915512) in the SAP97 gene in 1114 patients with schizophrenia and 1036 healthy-matched controls in a Han Chinese population through the improved multiplex ligation detection reaction (imLDR) technique. Then, we analyzed the association between this SNP and the patients' clinical symptoms and neurocognitive function. Our results showed that there were no significant differences in the genotype and allele frequencies between the patients and the controls for the rs3915512 polymorphism. However, patients with the rs3915512 polymorphism TT genotype had higher neurocognitive function scores (list learning scores, symbol coding scores, category instances scores and controlled oral word association test scores) than the subjects with the A allele (P = 4.72 × 10−5, 0.027, 0.027, 0.013, respectively). Our data are the first to suggest that the SAP97 rs3915512 polymorphism may affect neurocognitive function in patients with schizophrenia.
Highlights
Neurocognitive impairment has been described as a core manifestation of schizophrenia, with the impairments occurring mainly in memory, attention, and abstract thinking, etc., and at least two of these cognitive deficits occur in up to 70% of patients [1]
For the rs3915512 polymorphism, there was no significant difference in the genotype and allele frequency between the patients and the controls (P > 0.05)
The hypothesis that the SAP97 protein, which can interact with these neurotransmitter receptors [3,4,5], may play a role in schizophrenia is credible
Summary
Neurocognitive impairment has been described as a core manifestation of schizophrenia, with the impairments occurring mainly in memory, attention, and abstract thinking, etc., and at least two of these cognitive deficits occur in up to 70% of patients [1]. The SAP97 gene encodes the multidomain scaffolding proteins, which are abundantly expressed in neuronal synapses [2] and interact with a variety of neurotransmitter receptors, including NMDAR [3], α-amino-3-hydroxy-5-methyl4-isoxazolepropionic acid receptor (AMPAR) [4] and serotonin receptor (5-HTR) [5]. MacKenzie et al found in rat hippocampal slice cultures that SAP97 overexpression can drive NMDARs to synapses and enhance NMDA receptor excitatory postsynaptic currents (EPSCs) [2], and knockdown of SAP97 in another study was found to reduce the expression of AMPAR at the synaptic surface and inhibited NMDA and AMPA EPSCs [8]. We speculated that the SAP97 gene is a reasonable candidate gene for schizophrenia
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