Variants of the RELA gene are associated with schizophrenia and their startle responses.
2011
The pathogenesis of
schizophreniais 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
RELAgene and performed a gene-based association analysis using 1224 patients with
schizophreniaand 1663 controls. We found significant associations of three
SNPs(rs11820062: p=0.00011, rs2306365: p=0.0031, and rs7119750: p=0.0080) with
schizophreniaand stronger evidence for association in a multi-marker sliding window haplotype analysis (the lowest p=0.00006). The association between this gene and
schizophreniawas evident in male subjects but not in female subjects, when separately analyzed by gender. In
silicogenotype-gene expression analysis using web database and the WGAViewer software revealed that these three
schizophrenia-associated
SNPsmight be related to
RELAmRNA expression in immortalized B-lymphocytes. In
silicoanalysis also suggested the putative promoter
SNP, rs11820062, might disrupt the consensus transcription factor binding sequence of the androgen receptor. The impact of four
RELApolymorphisms on pre-pulse inhibition (PPI) was investigated in 53 patients with
schizophrenia. We provided evidence that at risk genotypes of three
SNPswere associated with deficits in PPI; however, there was no effect of the one non-risk
SNPon PPI. These findings suggest that variants of the
RELAgene are associated with risk for
schizophreniaand PPI deficits in a Japanese population.
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