An association study on polymorphisms in the PEA15, ENTPD4, and GAS2L1 genes and schizophrenia.

Our previous study examined a number of methamphetamine (METH)/phencyclidine (PCP)-reactive tags in rat brain, using a serial analysis of gene expression. Among human homologous genes, which matched METH/PCP-reactive tags, three human genes were identified: phosphoprotein enriched in astrocyte 15 (PEA15), ectonucleoside triphosphate diphosphohydrolase 4 (ENTPD4), and growth arrest-specific 2 like 1 (GAS2L1), which are localized in the chromosome 1q21.1, 8p21.3, and 22q12.2, respectively. We postulated that these genes are plausible candidate genes that play a role in pathogenesis for schizophrenia. Using tagging single-nucleotide polymorphisms (SNPs), we performed a case-control comparison for three SNPs in the PEA15 gene, and six SNPs in the GAS2L1 gene in a sample set of subjects (240 schizophrenia patients and 286 control subjects). Twelve SNPs in the ENTPD4 gene were analyzed in a subset of subjects (94 schizophrenia patients and 94 control subjects). No single SNP displayed a significant difference regarding the allelic frequency or genotypic distribution between the affected cases and controls for any of the genes examined. There was neither a significant difference in the frequency of three marker haplotype in the PEA15 gene or of six marker haplotype in the GAS2L1 gene between the cases and controls. The present study fails to provide evidence for the contribution of PEA15, ENTPD4, and GAS2L1 genes to the etiology of schizophrenia in the Japanese population.