Expression of candidate susceptibility gene in the cingulated cortex of brains from patients with schizophrenia : a postmortem study

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In our Scientific Research (C)(2) project from 2003 to 2004, we investigated gene expression in the cingulate and prefrontal cortices of postmortem brains of schizophrenia, in order to identify novel candidate genes for schizophrenia.1)A cDNA array was used to screen pools of samples from the cingulate or prefrontal cortex of patients with schizophrenia. Of the examined genes, 33 mRNA were increased and 22 were decreased. Quantitative reverse transcriptase (RT)-PCR, Western blot, or in situ hybridization analyses were done to confirm the results. We screened for genetic variations in the possible candidate genes and studied the association between schizophrenia and genetic polymorphisms.2)Using differential display, we identified a gene regulated by the delayed action of PCP in rat nucleus accumbens (NAcs). The cDNA clone obtained was identical to rat synapse-associated protein 90/postsynaptic density-95-associated protein 1 (SAPAP1). Immunoquantification using an anti-SAPAP1 antibody indicated that immunoreactivity for SAPAP1 increased in the NAcs of postmorten brains from unmedicated patients with schizophrenia. We identified a single nucleotide polymorphism in the SAPAP1/DAP-1 gene (1618A/G). However, a case-control study did not reveal a significant association between this polymorphism and schizophrenia.3)We found a novel missense polymorphism (Val38Met) in the Regulator of G-protein signaling 10 (RGS10) gene. A case-control study did not show a significant association between this polymorphism and schizophrenia.