炎症因子与甲状腺疾病的因果关联：孟德尔随机化研究-现代医学

炎症因子与甲状腺疾病的因果关联：孟德尔随机化研究

单位：1. 河北医科大学第一医院乳腺甲状腺诊疗中心, 河北石家庄 050031;
2. 河北医科大学第二医院营养科, 河北石家庄 050061

分类号：R736.1;R581.1;R581.2

出版年·卷·期（页码）：2025·53·第二期（203-210）

摘要：

目的：为了能进一步评估41种炎症因子与甲状腺疾病之间的因果关系，本研究进行了孟德尔随机化(MR)分析。方法：本研究暴露数据来源于一项有8 293名参与者的全基因组关联研究(GWAS)，结局数据来源于Sakaue等一项跨种族GWAS荟萃分析中的欧洲人群数据。采用逆方差加权法(IVW)作为主要的MR方法，辅以MR-Egger及加权中位数法，并进行了一系列相关的敏感性分析。采用Cochran Q检验评估结果的异质性，运用MR-Egger回归评估水平多效性，并且运用留一法(leave-one-out)评估因果关系不受任何单个单核苷酸多态性(SNP)的影响。结果：研究表明较高水平的血管内皮生长因子(VEGF)可能与甲状腺癌成正相关,受激活调节正常T细胞表达和分泌因子(RANTES)水平较高会使Graves病的发病风险降低，白介素IL-12p70、巨噬细胞炎性蛋白质1β(MIP-1β)及VEGF可能会促进桥本甲状腺炎的发生。结论： VEGF及RANTES分别可能在甲状腺癌及Graves病的发病机制中起重要作用，并且较高水平的IL-12p70和MIP-1β及VEGF可能与桥本甲状腺炎发生相关。这或许可以为甲状腺疾病的防治提供新思路。

Objective: To explore the potential causal relationship between 41 inflammatory cytokines and thyroid disorders, Mendelian randomization(MR) analysis was performed. Methods: Exposure data for this study were derived from a Genome-wide association study(GWAS) study of 8 293 participants, and outcome data were derived from European population data from a cross-racial GWAS Meta-analysis by Sakaue et al. Inverse variance weighted(IVW) method was adopted as the main MR method, supplemented by MR-Egger and weighted median method, and a series of relevant sensitivity analyses were carried out. Cochran Q test was used to evaluate the heterogeneity of the results, MR-Egger regression was used to evaluate the horizontal pleiotropy, and the "leave-one-out method" analysis was used to evaluate the causality independent of any single SNP. Results: Studies have shown that higher levels of vascular endothelial growth factor(VEGF) might be positively correlated with thyroid cancer(TC). Activated regulation of normal T-cell expression and secretion factors(RANTES) at higher levels could reduce the risk of Graves disease(GD), while interleukin IL-12p70, macrophage inflammatory protein 1 β(MIP-1β), and VEGF might promote the occurrence of Hashimoto's thyroiditis(HT). Conclusion: VEGF and RANTES may play important roles in the pathogenesis of TC and GD respectively. Besides, higher levels of IL-12p70, MIP-1β and VEGF may be associated with HT. This may provide new ideas for the prevention and treatment of thyroid disorders.

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