炎症反应与血管性痴呆(VaD)的发展有关。循环细胞因子调节炎症反应,对免疫系统很重要。为了进一步阐明免疫系统在VaD中的作用,我们使用孟德尔随机化(MR)全面和双向评估循环细胞因子在VaD中的作用.使用最先进的全基因组关联研究,我们主要评估了41种循环细胞因子的不同遗传水平是否会影响发生VaD的风险,反过来,VaD的遗传风险是否会影响这些循环细胞因子。我们使用逆方差加权(IVW)和其他几种MR方法来评估循环细胞因子和VaD之间的双向因果关系,并进行了敏感性分析。肿瘤坏死因子相关凋亡诱导配体(TRAIL)与VaD风险呈负相关[比值比(OR):0.74,95%置信区间(CI):0.60-0.92,P=0.007,0.007]。VaD与7种循环细胞因子相关:巨噬细胞炎性蛋白1b(MIP-1β)[OR:1.05,95%CI:1.01-1.08,P=0.009],白细胞介素-12p70(IL-12)[OR:1.04,95%CI:1.00-1.08,P=0.047],白细胞介素-17(IL-17)[OR:1.04,95%CI:1.00-1.07,P=0.038],白细胞介素-7(IL-7)[OR:1.07,95%CI:1.02-1.12,P=0.009],干扰素γ(IFN-γ)[OR:1.03,95%CI:1.00-1.07,P=0.046],粒细胞集落刺激因子(GCSF)[OR:1.06,95%CI:1.02-1.09,P=0.001],成纤维细胞生长因子(FGF)[P=0.001],和成纤维细胞生长因子(FGF)[P=0.001]。,成纤维细胞生长因子碱性(FGF-Basic)[OR:1.04,95%CI:1.01~1.08,P=0.02]呈正相关。循环细胞因子与VaD相关,需要进一步的研究来确定它们是否是预防或治疗VaD的有效干预目标。
Inflammatory responses are associated with the development of vascular dementia (VaD). Circulating cytokines modulate the inflammatory response and are important for the immune system. To further elucidate the role of the immune system in VaD, we used Mendelian randomization (MR) to comprehensively and bi-directionally assess the role of circulating cytokines in VaD. Using state-of-the-art genome-wide association studies, we primarily assessed whether different genetic levels of 41 circulating cytokines affect the risk of developing VaD and, in turn, whether the genetic risk of VaD affects these circulating cytokines. We used inverse variance weighting (IVW) and several other MR methods to assess the bidirectional causality between circulating cytokines and VaD, and performed sensitivity analyses. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was inversely associated with VaD risk [odds ratio (OR): 0.74, 95 % confidence interval (CI): 0.60-0.92, P = 0.007, 0.007]. VaD was associated with seven circulating cytokines: macrophage inflammatory protein 1b (MIP-1 beta) [OR: 1.05, 95 % CI: 1.01-1.08, P = 0.009], Interleukin-12p70 (IL-12) [OR: 1.04, 95 % CI: 1.00-1.08, P = 0.047], Interleukin-17 (IL-17) [OR: 1.04, 95 % CI: 1.00-1.07, P = 0.038], Interleukin-7 (IL-7) [OR: 1.07, 95 % CI: 1.02-1.12, P = 0.009], Interferon gamma (IFN-γ) [OR: 1.03, 95 % CI: 1.00-1.07, P = 0.046], Granulocyte-colony stimulating factor (GCSF) [OR: 1.06, 95 % CI: 1.02-1.09, P = 0.001], Fibroblast growth factor (FGF) [P = 0.001], and Fibroblast growth factor (FGF) [P = 0.001]. Fibroblast growth factor basic (FGF-Basic) [OR: 1.04, 95 % CI: 1.01-1.08, P = 0.02] were positively correlated. Circulating cytokines are associated with VaD, and further studies are needed to determine whether they are effective targets for intervention to prevent or treat VaD.