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Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain

Bernhard T Baune1*, Carsten Konrad2, Dominik Grotegerd3, Thomas Suslow35, Eva Birosova6, Patricia Ohrmann3, Jochen Bauer3, Volker Arolt3, Walter Heindel7, Katharina Domschke34, Sonja Schöning3, Astrid V Rauch3, Christina Uhlmann3, Harald Kugel7 and Udo Dannlowski23

Author Affiliations

1 Discipline of Psychiatry, School of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, 5005, Australia

2 Department of Psychiatry, University of Marburg, Marburg, Germany

3 Department of Psychiatry, University of Muenster, Muenster, Germany

4 Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany

5 Department of Psychosomatic Medicine and Psychotherapy, University of Leipzig, Leipzig, Germany

6 Supramolecular and Synthetic Biology Group, School of Pharmacy and Molecular Sciences, James Cook University, Brisbane, QLD, Australia

7 Department of Clinical Radiology, University of Muenster, Muenster, Germany

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Journal of Neuroinflammation 2012, 9:125  doi:10.1186/1742-2094-9-125

Published: 13 June 2012

Abstract

Background

Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated.

Methodology

In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs.

Principal findings/results

In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses.

Conclusions/significance

These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.

Keywords:
Genetics; Inflammation; Interleukin 6; Neuroprotection; Voxel-based morphometry