Open Access Research article

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

Xiangdong Deng1, Noriaki Sagata1, Naoko Takeuchi1, Masami Tanaka1, Hideaki Ninomiya2, Nakao Iwata3, Norio Ozaki4, Hiroki Shibata1* and Yasuyuki Fukumaki1

Author Affiliations

1 Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan

2 Fukuoka Prefectural Dazaifu Hospital Psychiatric Center, Dazaifu, Fukuoka, Japan

3 Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan

4 Department of Psychiatry, Graduate School of Medicine, Nagoya University, Nagoya, Japan

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BMC Psychiatry 2008, 8:58  doi:10.1186/1471-244X-8-58

Published: 18 July 2008

Abstract

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.