循环细胞因子和甲状腺功能减退之间的关联：一项两样本双向孟德尔随机化分析
Mendelian Randomization Investigation of the Causal Association between Circulating Cytokines and Hypothyroidism
DOI: 10.12677/acm.2025.1592695, PDF,    国家自然科学基金支持
作者: 周保才, 杨镇菘：青岛大学附属烟台毓璜顶医院胃肠外科，山东 烟台；青岛大学医学院，山东 青岛；鉴 谧：青岛大学附属烟台毓璜顶医院胃肠外科，山东 烟台；姜芳洁*：青岛大学附属烟台毓璜顶医院内分泌科，山东 烟台；姜立新*：烟台业达医院普外科，山东 烟台
关键词: 甲状腺功能减退症；循环细胞因子；孟德尔随机化研究；血清标志物；Hypothyroidism； Circulating Cytokines； Mendelian Randomization； Biomarkers
摘要: 目的：探讨甲状腺功能减退症风险与循环细胞因子的因果关系，并确定用于识别甲减高危人群的生物标志物。方法：本研究采用双向孟德尔随机化(mendelian randomization, MR)分析，基于欧洲人群甲状腺功能减退症的全基因组关联(genome-wide association, GWAS)研究数据。选择41种循环细胞因子相关的遗传突变作为本实验的工具变量。为确保研究结果可靠，我们还增加了敏感性分析(基因多效性、异质性和leave-one-out测试)和反向MR评估。结果：结果显示甲状腺功能减退症风险与白细胞介素-8 (Interleukin-8 levels, IL-8)和白细胞介素-9水平(Interleukin-9 levels, IL-9)之间存在很强的因果关系。单核细胞趋化蛋白-1 (Monocyte chemoattractant protein-1 levels, MCP-1)和巨噬细胞炎症蛋白1b (Macrophage inflammatory protein 1b levels, MIP-1b)尽管显示出了很强的相关性，但没有通过敏感性测试。MR分析表明IL-8和IL-9是潜在的甲状腺功能减退症预测生物标志物。结论：本项孟德尔随机研究明确了特定循环细胞因子与甲状腺功能减退症风险之间存在因果关系，为识别甲状腺功能减退症高风险人群提供新的可靠预测生物标志物，并为探索免疫系统与甲状腺功能的复杂相关性提供生物学证据。
Abstract: Objective: To explore the causal relationship between hypothyroidism risk and circulating cytokines and identify potential biomarkers for screening. Methods: This study employed a bidirectional Mendelian randomization (MR) analysis based on data from genome-wide association (GWAS) studies of hypothyroidism from people of European ancestry. The genetic variants associated with 41 circulating cytokines were selected as instrumental variables for this experiment. For robustness and consistency of findings, we conducted additional sensitivity analyses (Gene pleiotropy, heterogeneity, and leave-one-out testing) and reverse Mendelian randomization assessments. Results: The analysis revealed a strong causal relationship between hypothyroidism risk and Interleukin-8 levels (IL-8) and Interleukin-9 levels (IL-9). We except Monocyte chemoattractant protein-1 levels (MCP-1) and Macrophage inflammatory protein 1b levels (MIP-1b), which showed a strong correlation but don’t pass the sensitivity test. MR analyses indicated that IL-8 and IL-9 are potential hypothyroidism predictive biomarkers. Conclusion: This Mendelian randomized study offers valuable insights into the causal relationships between specific circulating cytokines and hypothyroidism risk. These findings have potential in developing new predictive biomarkers for hypothyroidism and may provide valuable information for subsequent studies to explore the complex association between the immune system and thyroid function.
文章引用：周保才, 鉴谧, 杨镇菘, 姜芳洁, 姜立新. 循环细胞因子和甲状腺功能减退之间的关联：一项两样本双向孟德尔随机化分析[J]. 临床医学进展, 2025, 15(9): 1870-1878. https://doi.org/10.12677/acm.2025.1592695

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