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Background  The synapse-associated protein 97 gene ( SAP97 ) encodes a regulatory scaffold protein for the localization of L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) type glutamate receptors. We have recently demonstrated nominally significant associations between  SAP97  gene and schizophrenia among Japanese males. The present study aimed to replicate these findings using an independent and larger sample.    Methods  We investigated seven  SAP97  single nucleotide polymorphisms (SNPs) that displayed a significant association with schizophrenia in our preceding study in an independent Japanese population consisting of a total of 393 unrelated patients with schizophrenia (232 males and 161 females) and 393 unrelated control subjects (211 males and 182 females).    Results  The SNP rs9843659 showed a significant genotypic association with male patients in a recessive model (p = 0.037). The analysis of the combined data from the current and prior studies also demonstrated a significant association of this SNP (p = 0.0039). The meta-analysis for the allele frequency covering the two studies yielded an odds ratio of 1.38.    Conclusions  The present study replicated the previously reported male-selective genetic association between the  SAP97  polymorphism and schizophrenia. These findings further support the possible involvement of the  SAP97  gene variation in the susceptibility to schizophrenia in males and in the genetic basis for sex differences in the disorder.

Further evidence for a male-selective genetic association of synapse-associated protein 97 (SAP97) gene with schizophrenia