循环炎症因子水平与辐射相关皮肤及皮下组织疾病双向孟德尔随机化分析  

Bidirectional Mendelian randomized analysis of circulating inflammatory factor levels and radiation-related skin and subcutaneous tissue diseases

作　　者：杨得富 尚峰 徐莹 阎英 YANG De-fu;SHANG Feng;XU Ying;YAN Ying(Department of Radiation Oncology,General Hospital of Northern Theater Command,Shenyang 110016,China)

机构地区：[1]北部战区总医院放射治疗科,辽宁沈阳110016

出　　处：《临床军医杂志》2024年第9期885-891,共7页Clinical Journal of Medical Officers

基　　金：辽宁省科技计划联合计划(2023JH2/101700111)。

摘　　要：目的探讨循环炎症因子水平与辐射相关皮肤和皮下组织疾病(RRDST)之间的因果关系。方法基于全基因组关联研究数据,采用5种孟德尔随机化(MR)方法分析血清中70种循环炎症因子水平与RRDST的关系。结果正向MR结果显示,嗜酸性粒细胞趋化因子(CCL11)(比值比=0.9418,95%可信区间0.8910~0.9955,P=0.0341)、趋化因子(CXCL)10(比值比=0.9295,95%可信区间0.8819~0.9797,P=0.0065)、骨保护素(OPG)(比值比=0.8683,95%可信区间0.7749~0.9730,P=0.0150)与RRDST之间存在显著负相关,CXCL6(比值比=1.1082,95%可信区间1.0361~1.1853,P=0.0028)、白细胞介素(IL)-15受体α(比值比=1.0800,95%可信区间1.0228~1.1404,P=0.0055)、白血病抑制因子受体(LIFR)(比值比=1.0734,95%可信区间1.0146~1.1357,P=0.0138)、单核细胞趋化蛋白(MCP-1)(比值比=1.0928,95%可信区间1.0350~1.1538,P=0.0014)、硫酸氨基转移酶(SULT)1A1(比值比=1.0665,95%可信区间1.0054~1.1313,P=0.0324)与RRDST之间存在显著正相关;敏感性分析证实了这些因果关系的稳健性;反向MR分析未发现RRDST与循环炎症因子水平存在显著的反向因果关系。结论正向和反向MR分析揭示了特定炎症因子水平与RRDST风险之间的显著因果关系,CCL11、CXCL10、OPG水平与RRDST风险显著负相关,而CXCL6、IL-15受体α、LIFR、MCP-1、SULT1A1水平与RRDST风险显著正相关。这些发现为理解RRDST的病理机制提供了新的见解,并为未来的临床和公共卫生干预措施提供了潜在的目标。Objective To investigate the causal relationship between levels of circulating inflammatory factor levels and radiation-related skin and subcutaneous tissue diseases(RRDST).Methods Based on Genome Wide Association Study data,five Mendelian randomization(MR)methods were used to analyze the relationship between serum levels of 70 circulating inflammatory factors and RRDST.Results Positive MR results showed that CC chemokine ligand 11(CCL11)(odds ratio=0.9418,95%confidence interval 0.8910-0.9955,P=0.0341),chemokines(CXCL)10(odds ratio=0.9295,95%confidence interval 0.8819-0.9797,P=0.0065),ostoeprotegerin(OPG)(odds ratio=0.8683,95%confidence interval 0.7749-0.9730,P=0.0150)were significantly negatively correlated with RRDST,CXCL6(odds ratio=1.1082,95%confidence interval 1.0361-1.1853,P=0.0028),interleukin(IL)-15 receptorα(odds ratio=1.0800,95%confidence interval 1.0228-1.1404,P=0.0055),leukemia inhibitory factor receptor(LIFR)(odds ratio=1.0734,95%confidence interval 1.0146-1.1357,P=0.0138),monocyte chemoattractant protein-1(MCP-1)(odds ratio=1.0928,95%confidence interval 1.0350-1.1538,P=0.0014),sulfotransferase(SULT)1A1(odds ratio=1.0665,95%confidence interval 1.0054-1.1313,P=0.0324)were positively correlated with RRDST.Sensitivity analysis confirmed the robustness of these causal relationships.Reverse MR analysis did not find a significant reverse causal relationship between RRDST and circulating inflammatory factor levels.Conclusion Forward and reverse MR analysis revealed a significant causal relationship between the levels of specific inflammatory factors and the risk of RRDST.CCL11,CXCL10 and OPG levels are significantly negatively correlated with the risk of RRDST.The levels of CXCL6,IL-15 receptorα,LIFR,MCP-1 and SULT1A1 are significantly positively correlated with the risk of RRDST.These findings provide new insights into understanding the pathological mechanisms of RRDST and provide potential targets for future clinical and public health interventions.

关 键 词：孟德尔随机化 循环炎症因子 辐射相关皮肤和皮下组织疾病 全基因组关联分析 

分 类 号：R54[医药卫生—心血管疾病]