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Background  Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the genes involved in glutametergic transmission. We report here association studies of schizophrenia with  SLC1A4 ,  SLC1A5  encoding neutral amino acid transporters ASCT1, ASCT2, and  SLC6A5 ,  SLC6A9  encoding glycine transporters GLYT2, GLYT1, respectively.    Methods  We initially tested the association of 21 single nucleotide polymorphisms (SNPs) distributed in the four gene regions with schizophrenia using 100 Japanese cases-control pairs and examined allele, genotype and haplotype association with schizophrenia. The observed nominal significance were examined in the full-size samples (400 cases and 420 controls).    Results  We observed nominally significant single-marker associations with schizophrenia in SNP2 ( P  = 0.021) and SNP3 ( P  = 0.029) of  SLC1A4 , SNP1 ( P  = 0.009) and SNP2 ( P  = 0.022) of  SLC6A5 . We also observed nominally significant haplotype associations with schizophrenia in the combinations of SNP2-SNP7 ( P  = 0.037) of  SLC1A4  and SNP1-SNP4 ( P  = 0.043) of  SLC6A5 . We examined all of the nominal significance in the Full-size Sample Set, except one haplotype with insufficient LD. The significant association of SNP1 of  SLC6A5  with schizophrenia was confirmed in the Full-size Sample Set ( P  = 0.018).    Conclusion  We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby  SLC6A5 , whereas  SLC1A4 ,  SLC1A5  and  SLC6A9  are unlikely to be major susceptibility genes for schizophrenia in the Japanese population.

bmc psychiatry

Association study of polymorphisms in the neutral amino acid transporter genes SLC1A4, SLC1A5 and the glycine transporter genes SLC6A5, SLC6A9with schizophrenia