Variants of the RELA gene are associated with schizophrenia and their startle responses

Ryota Hashimoto, Kazutaka Ohi, Yuka Yasuda, Motoyuki Fukumoto, Hidenaga Yamamori, Hidetoshi Takahashi, Masao Iwase, Tomo Okochi, Hiroaki Kazui, Osamu Saitoh, Masahiko Tatsumi, Nakao Iwata, Norio Ozaki, Kunitoshi Kamijima, Hiroshi Kunugi, Masatoshi Takeda

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Abstract

The pathogenesis of schizophrenia is thought to involve aberrant immune and inflammatory responses. Nuclear factor kappa B (NF-κB) has important roles in the immune and inflammatory responses. The v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) gene encodes the major component of the NF-κB complex. We genotyped four single-nucleotide polymorphisms (SNPs) in the RELA gene and performed a gene-based association analysis using 1224 patients with schizophrenia and 1663 controls. We found significant associations of three SNPs (rs11820062: p0.00011, rs2306365: p0.0031, and rs7119750: p0.0080) with schizophrenia and stronger evidence for association in a multi-marker sliding window haplotype analysis (the lowest p0.00006). The association between this gene and schizophrenia was evident in male subjects but not in female subjects, when separately analyzed by gender. In silico genotype-gene expression analysis using web database and the WGAViewer software revealed that these three schizophrenia-associated SNPs might be related to RELA mRNA expression in immortalized B-lymphocytes. In silico analysis also suggested the putative promoter SNP, rs11820062, might disrupt the consensus transcription factor binding sequence of the androgen receptor. The impact of four RELA polymorphisms on pre-pulse inhibition (PPI) was investigated in 53 patients with schizophrenia. We provided evidence that at risk genotypes of three SNPs were associated with deficits in PPI; however, there was no effect of the one non-risk SNP on PPI. These findings suggest that variants of the RELA gene are associated with risk for schizophrenia and PPI deficits in a Japanese population.

Original languageEnglish
Pages (from-to)1921-1931
Number of pages11
JournalNeuropsychopharmacology
Volume36
Issue number9
DOIs
Publication statusPublished - 01-08-2011

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Hashimoto, R., Ohi, K., Yasuda, Y., Fukumoto, M., Yamamori, H., Takahashi, H., Iwase, M., Okochi, T., Kazui, H., Saitoh, O., Tatsumi, M., Iwata, N., Ozaki, N., Kamijima, K., Kunugi, H., & Takeda, M. (2011). Variants of the RELA gene are associated with schizophrenia and their startle responses. Neuropsychopharmacology, 36(9), 1921-1931. https://doi.org/10.1038/npp.2011.78