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.

• Authors: Christa Hohoff, Gerald Ponath, Christine M Freitag, Florian Kästner, Petra Krakowitzky, Katharina Domschke, Katja Koelkebeck, Frank Kipp, Christof von Eiff, Jürgen Deckert, Matthias Rothermundt
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 153B Issue 1 Pg. 291-7 (Jan 05 2010) ISSN: 1552-485X [Electronic] United States
• PMID: 19330775 (Publication Type: Journal Article)
• Copyright: (c) 2009 Wiley-Liss, Inc.

Chemical References

• Nerve Growth Factors
• RNA, Messenger
• S100 Calcium Binding Protein beta Subunit
• S100 Proteins
• S100B protein, human
• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins
• Receptor, Serotonin, 5-HT1A

Topics

• Humans
• Nerve Growth Factors (blood, genetics)
• Polymorphism, Single Nucleotide
• RNA, Messenger (genetics)
• Receptor, Serotonin, 5-HT1A (genetics)
• Risk Factors
• S100 Calcium Binding Protein beta Subunit
• S100 Proteins (blood, genetics)
• Serotonin Plasma Membrane Transport Proteins (genetics)