Association of SNPs linked to increased expression of SLC1A1 with schizophrenia

作者：Horiuchi Yasue; Iida Syuhei; Koga Minori; Ishiguro Hiroki; Iijima Yoshimi; Inada Toshiya; Watanabe Yuichiro; Someya Toshiyuki; Ujike Hiroshi; Iwata Nakao; Ozaki Norio; Kunugi Hiroshi; Tochigi Mamoru; Itokawa Masanari; Arai Makoto; Niizato Kazuhiro; Iritani Shuji; Kakita Akiyoshi; Takahashi Hitoshi; Nawa Hiroyuki; Arinami Tadao^*

来源：American Journal of Medical Genetics Part B-Neuropsychiatric Genetics, 2012, 159B(1): 30-37.

DOI：10.1002/ajmg.b.31249

• transporters
• glutamate
• postmortem brain
• antipsychotics

Glutamate is one of the key molecules involved in signal transduction in the brain, and dysfunction of glutamate signaling could be linked to schizophrenia. The SLC1A1 gene located at 9p24 encodes the glutamate transporter EAAT3/EAAC1. To investigate the association between the SLC1A1 gene and schizophrenia in the Japanese population, we genotyped 19 tagging single nucleotide polymorphisms (tagSNPs) in the SLC1A1 gene in 576 unrelated individuals with schizophrenia and 576 control subjects followed by replication in an independent casecontrol study of 1,344 individuals with schizophrenia and 1,344 control subjects. In addition, we determined the boundaries of the copy number variation (CNV) region in the first intron (Database of Genomic Variants, chr9:4516796-4520549) and directly genotyped the CNV because of significant deviation from the HardyWeinberg equilibrium. The CNV was not associated with schizophrenia. Four SNPs showed a possible association with schizophrenia in the screening subjects and the associations were replicated in the same direction (nominal allelic P%26lt;0.05), and, among them, an association with rs7022369 was replicated even after Bonferroni correction (allelic nominal P=5x10-5, allelic corrected P=2.5x10-4, allelic odds ratio, 1.30; 95% CI: 1.14-1.47 in the combined subjects). Expression analysis quantified by the real-time quantitative polymerase chain reaction in the postmortem prefrontal cortex of 43 Japanese individuals with schizophrenia and 11 Japanese control subjects revealed increased SLC1A1 expression levels in individuals homozygous for the rs7022369 risk allele (P=0.003). Our findings suggest the involvement of SLC1A1 in the pathogenesis of schizophrenia.

• 出版日期2012-1