Mihailova Snezhina, Ivanova-Genova Elena, Lukanov Tzvetelin, Stoyanova Vesela, Milanova Vihra, Naumova Elissaveta
Department of Clinical Immunology, University Hospital "Alexandrovska", Medical University, 1, "G. Sofiisky" Str., Sofia 1431, Bulgaria.
Department of Psychiatry, University Hospital "Alexandrovska", Medical University, 1, G. Sofiisky Str., Sofia 1431, Bulgaria.
J Neuroimmunol. 2016 Apr 15;293:123-128. doi: 10.1016/j.jneuroim.2016.03.005. Epub 2016 Mar 9.
In the last decade it was found that functional polymorphisms in the promoter and/or coding regions of regulatory genes are likely to pre-determine the phenotype manifestation of a certain cytokine profile, and thus could be used as disease-associated markers. Having in mind the hypothesis of impaired cytokine regulation in depressive disorder, as well as the diverse population-dependent results for cytokine polymorphisms, we investigated the relation between the cytokine gene polymorphisms of key pro- and anti-inflammatory cytokines (TNF-α, TGF-β, IL-10, IL-6, IFN-γ) and susceptibility as well as clinical course of depression in Bulgarians. The study included 80 patients with depression (50 women and 30 men) and 50 healthy controls. Simultaneous analysis of eight polymorphic positions in the cytokine genes listed was performed by PCR-SSP method. The results revealed significant predominance of TGF-β TT (+869) genotype (previously described as predicting low expression activity of TGF-β) in patients (41.3%) compared to healthy subjects (21.2%) (p=0.05, OR=2.62). Furthermore T/T G/C combined genotype (+869, +915) in the same gene was negatively associated with disease recurrence. Additionally we found that certain IL-10 genotypes associated with low gene expression seemed to shape moderate disease manifestation. In conclusion our results mainly demonstrated prevalence of a low-expression TGF-β1 profile in the patients. Thus, although in an indirect way, we supported the hypothesis of impaired immunosuppression by means of Th3 regulation in major depressive disorders.
在过去十年中发现，调节基因启动子和/或编码区的功能多态性可能预先决定某种细胞因子谱的表型表现，因此可作为疾病相关标志物。考虑到抑郁症中细胞因子调节受损的假说，以及细胞因子多态性在不同人群中的不同结果，我们研究了关键促炎和抗炎细胞因子（TNF-α、TGF-β、IL-10、IL-6、IFN-γ）的基因多态性与保加利亚人抑郁症易感性及临床病程之间的关系。该研究纳入了80例抑郁症患者（50名女性和30名男性）和50名健康对照者。采用PCR-SSP方法对所列细胞因子基因中的8个多态性位点进行同步分析。结果显示，与健康受试者（21.2%）相比，患者中TGF-β TT（+869）基因型（先前描述为预测TGF-β低表达活性）显著占优势（41.3%）（p=0.05，OR=2.62）。此外，同一基因中的T/T G/C联合基因型（+869，+915）与疾病复发呈负相关。此外，我们发现某些与低基因表达相关的IL-10基因型似乎决定了中度疾病表现。总之，我们的结果主要表明患者中低表达TGF-β1谱的普遍性。因此，尽管是以间接方式，我们支持了重度抑郁症中通过Th3调节免疫抑制受损的假说。
