Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia

Xiangdong Deng1, Hiroki Shibata1, Naoko Takeuchi1, Shinako Rachi1, Mayumi Sakai1, Hideaki Ninomiya2, Nakao Iwata3, Norio Ozaki4, Yasuyuki Fukumaki1
1Division of Disease Genes, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
2Fukuoka Prefectural Dazaifu Hospital Psychiatric Center, Dazaifu, Fukuoka, Japan
3Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
4Department of Psychiatry, Graduate School of Medicine, Nagoya University, Nagoya, Japan

Tóm tắt

AbstractBased on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We initially performed the screening of the total 25 single nucleotide polymorphisms (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases and 100 out of 420 Japanese controls. After controlling the false discovery rate (FDR) at level 0.05, we observed significant associations of schizophrenia with a genotype of SNP4 (rs2097837, P = 0.007) and with haplotypes of SNP2‐SNP5 (P = 7.5 × 10−5) and SNP3‐SNP5 (P = 9.0 × 10−4) in the SLC1A6 region. The haplotype of SNP2‐SNP5 of SLC1A6 even showed marginally significant association with the disease in the full‐size sample (400 cases and 420 controls, P = 0.031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population. © 2006 Wiley‐Liss, Inc.

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