Association study of polymorphisms in the neutral amino acid transporter genes <it>SLC1A4</it>, <it>SLC1A5 </it>and the glycine transporter genes <it>SLC6A5</it>, <it>SLC6A9 </it>with schizophrenia

• Main Authors: Shibata Hiroki, Ozaki Norio, Ninomiya Hideaki, Iwata Nakao, Tanaka Masami, Takeuchi Naoko, Sagata Noriaki, Deng Xiangdong, Fukumaki Yasuyuki
• Format: Article
• Language: English
• Published: BMC 2008-07-01
• Series: BMC Psychiatry
• Online Access: http://www.biomedcentral.com/1471-244X/8/58

<p>Abstract</p> <p>Background</p> <p>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 <it>SLC1A4</it>, <it>SLC1A5 </it>encoding neutral amino acid transporters ASCT1, ASCT2, and <it>SLC6A5</it>, <it>SLC6A9 </it>encoding glycine transporters GLYT2, GLYT1, respectively.</p> <p>Methods</p> <p>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).</p> <p>Results</p> <p>We observed nominally significant single-marker associations with schizophrenia in SNP2 (<it>P </it>= 0.021) and SNP3 (<it>P </it>= 0.029) of <it>SLC1A4</it>, SNP1 (<it>P </it>= 0.009) and SNP2 (<it>P </it>= 0.022) of <it>SLC6A5</it>. We also observed nominally significant haplotype associations with schizophrenia in the combinations of SNP2-SNP7 (<it>P </it>= 0.037) of <it>SLC1A4 </it>and SNP1-SNP4 (<it>P </it>= 0.043) of <it>SLC6A5</it>. 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 <it>SLC6A5 </it>with schizophrenia was confirmed in the Full-size Sample Set (<it>P </it>= 0.018).</p> <p>Conclusion</p> <p>We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby <it>SLC6A5</it>, whereas <it>SLC1A4</it>, <it>SLC1A5 </it>and <it>SLC6A9 </it>are unlikely to be major susceptibility genes for schizophrenia in the Japanese population.</p>