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


METHODS
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/resultsIn 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, p(uncorrected) = 0.0002; p(AlphaSim-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
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.
Discipline of Psychiatry, School of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, Australia. bernhard.baune@adelaide.edu.au
Bernhard T
BT
Baune
Carsten
C
Konrad
Dominik
D
Grotegerd
Thomas
T
Suslow
Eva
E
Birosova
Patricia
P
Ohrmann
Jochen
J
Bauer
Volker
V
Arolt
Walter
W
Heindel
Katharina
K
Domschke
Sonja
S
Schöning
Astrid V
AV
Rauch
Christina
C
Uhlmann
Harald
H
Kugel
Udo
U
Dannlowski
D000328:Adult; D000367:Age Factors; D000483:Alleles; D001921:Brain / Q000166:cytology* / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
C508600:IL6 protein, human; D015850:Interleukin-6