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

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).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.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.Schizophrenia is a serious psychiatric disorder with a high prevalence of nearly 1% and a wide variety of mental dysfunctions that are only partially improved by the current antipsychotic drugs. It is well accepted that multiple susceptibility genes may be involved in the pathogenesis of schizophrenia [1], and the search for such genes has produced promising results [2]. To obtain a further insight into the genetic factors, we have investigated the possible association between schizophrenia and the genes that are related to the impaired N-methyl-D-aspartate (NMDA) receptor-mediated glutamate neurotransmission and the development-dependent onset of schizophrenia, because 1) NMDA receptor antagonists, such as phencyclidine (PCP) and ketamine, cause the psychotic symptoms indistinguishable from those of schizophrenia [3,4], 2) the onset of schizophrenia and the above psychotomimetic effects typically occur after puberty [5-9], and 3) in experimental animals, th