Associations of Tumor Necrosis Factor-α and Interleukin-1β Levels and Polymorphisms with Post-Stroke Depression
Associations of Tumor Necrosis Factor-α and Interleukin-1β Levels and Polymorphisms with Post-Stroke Depression
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DOI：
10.1016/j.jagp.2017.07.012
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发表时间：
2017-12-01
影响因子：
7.2
通讯作者：
Cho, Ki-Hyun
中科院分区：
文献类型：
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作者：
Kim, Jae-Min;Kang, Hee-Ju;Cho, Ki-Hyun
目的：促炎细胞因子与中风后抑郁症（PSD）的病理生理学有关，其产生水平受到遗传多态性转录活性的影响。本研究旨在探讨血清中肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β对PSD风险的作用，同时考虑TNF-α-850C/T和-308G/A多态性以及IL-1β-511C/T和+3953C/T多态性。方法：共有 286 名患者在中风后 2 周接受评估，其中 222 名患者 (78%) 于 1 年后接受随访。两次检查期间均根据《精神疾病诊断与统计手册》第四版（DSM-IV）标准诊断抑郁（重度或轻度）障碍；两周时对细胞因子浓度、多态性以及人口统计和临床协变量进行评估。使用多元逻辑回归模型研究了 TNF-α 和 IL-1β 浓度以及基因型对 PSD 状态的影响。结果：在 -850T 等位基因存在的情况下，两周时较高的 TNF-α 水平与 PSD 相关，并具有显着的相互作用项；在存在具有临界显着相互作用项的-511T等位基因以及没有显着相互作用项的任何+3953C/T多态性的情况下，较高的IL-1β水平与2周时的PSD相关。 1 年时未发现与 PSD 的关联。结论：这些发现表明 TNF-α 和 IL-1 β 血清水平在 PSD 风险方面发挥着重要作用，特别是在中风急性期和具有遗传易感性的患者中。
Objective: Proinflammatory cytokines have been implicated in the pathophysiology of post-stroke depression (PSD), and their production levels are influenced by the transcriptional activity of genetic polymorphisms. The present study aimed to investigate the roles of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta in the serum on the risk of PSD while taking into account the TNF-alpha-850C/T and -308G/A polymorphisms and the IL-1 beta -511C/T and +3953C/T polymorphisms. Methods: A total of 286 patients were evaluated at 2 weeks post stroke and 222 (78%) of these patients were followed up 1 year later. Depressive (major or minor) disorders were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria during both examinations; evaluations of cytokine concentrations and polymorphisms and demographic and clinical covariates were performed at 2 weeks. The effects of TNF-alpha and IL-1 beta concentrations and genotypes on PSD status were investigated using multivariate logistic regression models. Results: Higher TNF-alpha levels were associated with PSD at 2 weeks in the presence of the -850T allele with a significant interaction term; higher IL-1 beta levels were associated with PSD at 2 weeks in the presence of the -511T allele with a borderline significant interaction term and with any +3953C/T polymorphism without a significant interaction term. No associations were found with PSD at 1 year. Conclusions: These findings indicate the important roles that TNF-alpha and IL-1 beta serum levels play regarding the risk of PSD, particularly during the acute phase of stroke and in patients with genetic susceptibility.