Risk variants in the S100B gene predict elevated S100B serum concentrations in healthy individuals

Abstract

Several lines of evidence suggest an important role of the S100B protein and its coding gene in different neuropathological and psychiatric disorders like dementia, bipolar affective disorders and schizophrenia. To clarify whether a direct link exists between gene and gene product, that is, whether S100B variants directly modulate S100B serum concentration, 196 healthy individuals were assessed for S100B serum concentrations and genotyped for five potentially functional S100B SNPs. Functional variants of the serotonergic genes 5-HT1A and 5-HTT possibly modulating S100B serum levels were also studied. Further, publicly available human postmortem gene expression data were re-analyzed to elucidate the impact of S100B, 5-HT1A and 5-HTT SNPs on frontal cortex S100B mRNA expression. Several S100B SNPs, particularly rs9722, and the S100B haplotype T-G-G-A (including rs2186358-rs11542311-rs2300403-rs9722) were associated with elevated S100B serum concentrations (Bonferroni corrected P < 0.05). Of these, rs11542311 was also associated with S100B mRNA expression directly (Bonferroni corrected P = 0.05) and within haplotype G-A-T-C (rs11542311-rs2839356-rs9984765-rs881827; P = 0.004), again with the G-allele increasing S100B expression. Our results suggest an important role of S100B SNPs on S100B serum concentrations and S100B mRNA expression. It hereby links recent evidence for both, the impact of S100B gene variation on various neurological or psychiatric disorders like dementia, bipolar affective disorders and schizophrenia and the strong relation between S100B serum levels and these disorders.

Risk variants in the S100B gene, associated with elevated S100B levels, are also associated with visuospatial disability of schizophrenia

“…Note that both the A allele of rs9722 and the G allele of rs1051169 have also been suggested as risk factors for elevated S100B levels in serum and/or the frontal cortex [12]. Additionally, elevated S100B levels have been shown to be associated with poor cognitive function in schizophrenia patients [19].…”

“…More importantly for this study, Liu and colleagues [14], using 384 schizophrenia patients and 401 controls of Han Chinese origin, found that schizophrenia was significantly associated with haplotypes composed of rs1051169 and rs9722 (two SNPs in the S100B gene) and marginally associated with rs1051169 alone. Interestingly, both of these SNPs have been found to affect S100B gene expression [12]. It is not known, however, whether these potentially functional SNPs can also affect cognitive functions in schizophrenia patients.…”

S100B Serum Levels and Word Memory Processing in Remitted Major Depression as Reflected by Brain Potentials

“…Just recently, it has been shown that S100B single nucleotide polymorphisms have a strong impact on S100B mRNA and serum concentration [37] . We need to investigate to what extent the genetic variation influences ERP patterns in patients with affective disorders.…”

Functional assessment of a promoter polymorphism in S100B, a putative risk variant for bipolar disorder

“…DNA samples and corresponding serum S100B measurements from German healthy control individuals (n ¼ 196) were kindly provided by Christa Hohoff from the Department of Psychiatry, University of M€ unster, Germany. Preparation of the DNA samples is described elsewhere [Hohoff et al, 2010].Demographic data on all samples is supplied in supplementary Table A. All 350 Irish and German samples were genotyped for rs3788266 using the predesigned Taqman Ò Assay (ID: C_25800807_10) from Applied Biosystems (Warrington, UK).…”