Discipline of Psychiatry, School of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, Australia.
J Neuroinflammation. 2012 Jul 6;9:125. doi: 10.1186/1742-2094-9-125.
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.
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/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.
白细胞介素 6（IL-6）等细胞因子在神经精神疾病中有双重作用。对于细胞因子基因的神经退行性和神经增殖特性的遗传易感性知之甚少。在这项研究中，研究了几种 IL-6 多态性在大脑形态中的潜在双重作用。
在一个大型健康个体样本中（N=303），使用基于体素的形态测量学（VBM）分析了 IL-6（rs1800795；rs1800796、rs2069833、rs2069840）基因变异与脑容量（灰质体积）之间的关联。单核苷酸多态性（SNP）的选择遵循标记 SNP 方法（例如，Stampa 算法），使用四个标记 SNP 捕获 IL-6 基因的 97.08%变异。
主要发现/结果：在全脑分析中，多态性 rs1800795（-174 C/G）显示出基因型的强烈主效应（43 CC 对 150 CG 对 100 GG；x=24，y=-10，z=-15；F(2,286)=8.54，p(未校正)=0.0002；p(AlphaSim 校正)=0.002；簇大小 k=577）在右侧海马头部。与杂合子受试者相比，G-等位基因的纯合子携带者的海马灰质体积明显更大。在全脑分析中，没有其他研究的 SNP 与灰质体积有显著相关性。
结论/意义：这些发现表明 SNP rs1800795 的 G-等位基因可能对海马体积有神经保护作用。有必要在精神病患者人群中，特别是在受影响的海马（例如，受虐待、压力）的患者中研究该 SNP 的作用。
