title: Variants of the RELA gene are associated with schizophrenia and their startle responses.
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: p=0.00011, rs2306365: p=0.0031, and rs7119750: p=0.0080) with schizophrenia and stronger evidence for association in a multi-marker sliding window haplotype analysis (the lowest p=0.00006). 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.
authors: Molecular Research Center for Children's Mental Dev., United Graduate School of Child Dev. Osaka Univ. Kanazawa Univ.and Hamamatsu Univ.School of Med. Osaka, Japan. ashimor@psy.med.osaka-u.ac.jp
authors: Ryota
authors: R
authors: Hashimoto
authors: Kazutaka
authors: K
authors: Ohi
authors: Yuka
authors: Y
authors: Yasuda
authors: Motoyuki
authors: M
authors: Fukumoto
authors: Hidenaga
authors: H
authors: Yamamori
authors: Hidetoshi
authors: H
authors: Takahashi
authors: Masao
authors: M
authors: Iwase
authors: Tomo
authors: T
authors: Okochi
authors: Hiroaki
authors: H
authors: Kazui
authors: Osamu
authors: O
authors: Saitoh
authors: Masahiko
authors: M
authors: Tatsumi
authors: Nakao
authors: N
authors: Iwata
authors: Norio
authors: N
authors: Ozaki
authors: Kunitoshi
authors: K
authors: Kamijima
authors: Hiroshi
authors: H
authors: Kunugi
authors: Masatoshi
authors: M
authors: Takeda
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