抄録
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.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 1921-1931 |
| ページ数 | 11 |
| ジャーナル | Neuropsychopharmacology |
| 巻 | 36 |
| 発行部数 | 9 |
| DOI | |
| 出版物ステータス | Published - 01-08-2011 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Psychiatry and Mental health
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Variants of the RELA gene are associated with schizophrenia and their startle responses. / Hashimoto, Ryota; Ohi, Kazutaka; Yasuda, Yuka; Fukumoto, Motoyuki; Yamamori, Hidenaga; Takahashi, Hidetoshi; Iwase, Masao; Okochi, Tomo; Kazui, Hiroaki; Saitoh, Osamu; Tatsumi, Masahiko; Iwata, Nakao; Ozaki, Norio; Kamijima, Kunitoshi; Kunugi, Hiroshi; Takeda, Masatoshi.
：: Neuropsychopharmacology, 巻 36, 番号 9, 01.08.2011, p. 1921-1931.研究成果: Article
TY - JOUR
T1 - Variants of the RELA gene are associated with schizophrenia and their startle responses
AU - Hashimoto, Ryota
AU - Ohi, Kazutaka
AU - Yasuda, Yuka
AU - Fukumoto, Motoyuki
AU - Yamamori, Hidenaga
AU - Takahashi, Hidetoshi
AU - Iwase, Masao
AU - Okochi, Tomo
AU - Kazui, Hiroaki
AU - Saitoh, Osamu
AU - Tatsumi, Masahiko
AU - Iwata, Nakao
AU - Ozaki, Norio
AU - Kamijima, Kunitoshi
AU - Kunugi, Hiroshi
AU - Takeda, Masatoshi
PY - 2011/8/1
Y1 - 2011/8/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=79960311869&partnerID=8YFLogxK
U2 - 10.1038/npp.2011.78
DO - 10.1038/npp.2011.78
M3 - Article
C2 - 21593732
AN - SCOPUS:79960311869
VL - 36
SP - 1921
EP - 1931
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 9
ER -