Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain
Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain
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DOI：
10.1186/1742-2094-9-125
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发表时间：
2012-06-13
影响因子：
9.3
通讯作者：
Dannlowski, Udo
中科院分区：
文献类型：
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作者：
Baune, Bernhard T.;Konrad, Carsten;Dannlowski, Udo
背景：白介素6(IL-6)等细胞因子参与了神经精神障碍的双重功能。细胞因子基因对神经退行性变和神经增殖性的遗传易感性知之甚少。本研究旨在探讨多种IL-6基因多态性在脑形态结构中的双重作用。方法：在大样本健康人群(N=303)中，采用体素形态计量学方法分析IL-6基因变异(rs1800795；rs1800796，rs2069833，rs2069840)与脑体积(灰质体积)的关系。单核苷酸多态(SNPs)的选择遵循标签SNP方法(例如Stampa算法)，使用四个标签SNP产生了97.08%的IL-6基因变异。主要发现/结果在全脑分析中，rs1800795(-174C/G)多态在右侧海马头显示了很强的主效应(43CC比150CG比100GG；x=24，y=-10，z=-15；F(2,286)=8.54，p(未校正)=0.0002；p(AlphaSim校正)=0.002；聚类大小k=577)。与杂合子受试者相比，G等位基因纯合携带者的海马灰质体积显著增大。在全脑分析中，其他被研究的SNPs均未显示与灰质体积显著相关。结论/意义：这些发现提示SNP rs1800795的G等位基因对海马体体积可能具有神经保护作用。有必要研究这种SNP在精神病人群中的作用，特别是在那些海马体受损(例如，由于虐待、压力)的人群中。
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, 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/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.