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An association analysis of synapse-associated protein 97 (SAP97) gene in schizophrenia

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

SAP97 gene encodes the synaptic scaffolding PDZ proteins that interact with the l-alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionate (AMPA), kainate and N-methyl-d-aspartate (NMDA) type glutamate receptors. Because the disturbed glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia, we investigated association between the SAP97 gene and schizophrenia. We genotyped 23 SNPs capturing the known common haplotype variations of the gene in a sample comprising 229 schizophrenic patients and 214 matched controls. In a single marker analysis, ten SNPs displayed nominally significant (P < 0.05) association with schizophrenia, although the P values of these SNPs were non-significant after the Bonferroni correction. We also compared haplotype estimates based on case—control genotypes and observed significant association of eight-two- and three- SNP haplotypes with schizophrenia following permutation-based correction. Further examination of the above series of SNPs or haplotypes in each gender revealed significant associations between some of these SNPs or haplotypes and the disorder only in males. The present findings suggest that the SAP97 gene may be a susceptibility factor in male schizophrenics and that the modification of the glutamate receptors-SAP97 signaling pathway could be involved in the disease pathophysiology.

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Acknowledgments

This study was partly supported by research grants-in-aid from the Research Development Corporation of Japan, the Ministry of Health, Labour and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Authors and Affiliations

  1. Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, 1-5-45, Bunkyo-ku, Tokyo, 113-8519, Japan

    Junko Sato, Dai Shimazu, Naoki Yamamoto & Toru Nishikawa

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  1. Junko Sato
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  2. Dai Shimazu
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  3. Naoki Yamamoto
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  4. Toru Nishikawa
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Correspondence to Toru Nishikawa.

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Sato, J., Shimazu, D., Yamamoto, N. et al. An association analysis of synapse-associated protein 97 (SAP97) gene in schizophrenia. J Neural Transm 115, 1355–1365 (2008). https://doi.org/10.1007/s00702-008-0085-9

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  • DOI: https://doi.org/10.1007/s00702-008-0085-9

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