背景:先前的观察性研究报道了循环炎性细胞因子与脑小血管病(CSVD)之间的相关性。然而,这种关联的因果关系是不确定的。这项研究使用孟德尔随机化来研究循环炎性细胞因子对CSVD神经影像学变化的因果关系。
方法:本研究利用来自全基因组关联研究的41种炎性细胞因子和3种CSVD神经影像学标志物的遗传变异来评估双样本孟德尔随机化方法中的因果效应。以方差加权分析为主要分析方法,并采用敏感性分析进一步验证了结果的稳健性。
结果:IL-18增加与白质高强度(WMH)和平均弥散率(MD)增加相关(β=0.034,95%CI0.002,0.065,P=0.038,β=0.157,95%CI0.015,0.299,P=0.030)。然而,IL-18升高与各向异性分数(FA)降低相关(β=-0.141,95%CI-0.279,-0.002,P=0.047).单核细胞趋化蛋白-1(MCP-1)升高与FA降低相关(β=-0.278,95%CI-0.502,-0.054,P=0.015)。IL-10水平和IL-2ra水平升高与MD风险降低相关(β=-0.228,95%CI-0.448,-0.009,p=0.041;β=-0.204,95%CI=-0.377,-0.031,p=0.021)。
结论:这项研究表明,IL-18和MCP-1水平升高与白质微结构损伤有关,IL-10和IL-2ra水平升高与MD降低相关。
BACKGROUND: Previous observational studies have reported the correlation between circulating inflammatory cytokines and cerebral small vessel disease (CSVD). However, the causality of this association is uncertain. This
study used Mendelian randomization to investigate the causal effect of circulating inflammatory cytokines on neuroimaging changes in CSVD.
METHODS: This
study utilized genetic variances of 41 inflammatory cytokines and 3 neuroimaging markers of CSVD from genome-wide association studies to assess the causal effects in a two-sample Mendelian randomization approach. Inverse variance weighted analysis was used as the main analytical method, and sensitivity analysis was used to further validate the robustness of the results.
RESULTS: Increased IL-18 was associated with increased white matter hyperintensity (WMH) and mean diffusivity (MD) (β = 0.034, 95 % CI 0.002, 0.065, P=0.038, β = 0.157, 95 % CI 0.015, 0.299, P=0.030). However, increased IL-18 was associated with decreased fractional anisotropy (FA) (β = -0.141, 95 % CI -0.279, -0.002, P=0.047). Increased monocyte chemotactic protein-1(MCP-1) was associated with decreased FA (β = -0.278, 95 % CI -0.502, -0.054, P=0.015). Increased IL-10 levels and IL-2ra levels were associated with decreased risks of MD (β = -0.228, 95 % CI -0.448, -0.009, p = 0.041; β = -0.204, 95 % CI=-0.377, -0.031, p = 0.021).
CONCLUSIONS: This
study revealed that increased levels of IL-18 and MCP-1 were associated with white matter microstructural injury, and increased levels of IL-10 and IL-2ra were associated with decreased MD.