遗传支持 91 种循环炎症蛋白与特应性皮炎之间的因果关联：一项两样本孟德尔随机化试验。
Genetic support for the causal association between 91 circulating inflammatory proteins and atopic dermatitis: A two-sample Mendelian randomization trial.
机构信息
Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
出版信息
Skin Res Technol. 2024 Aug;30(8):e13872. doi: 10.1111/srt.13872.
BACKGROUND
Atopic dermatitis (AD) is a refractory disease that occurs in clinical practice. One of the most common inflammatory skin diseases, its occurrence and development are related to inflammation. Nevertheless, the precise nature of the relationship between circulating inflammatory proteins and AD remains uncertain.
METHODS
A two-sample MR analysis was performed to determine the causal relationship between the expression of 91 circulating inflammatory proteins and AD by using genome-wide association study (GWAS) summary statistics data from the FinnGen consortia. The robustness of the MR results was assessed by means of sensitivity analysis.
RESULTS
The causal relationship between the expression of nine specific circulating inflammatory proteins and AD was corroborated by the inverse variance weighted (IVW) method. The findings indicated that three circulating inflammatory proteins, namely, interleukin-18 receptor 1 [OR (CI) = 1.08 (1.05-1.11); p = 0.000001)], interleukin-8 [OR (CI) = 1.07 (1.00-1.14); p = 0.036244)], and tumor necrosis factor ligand superfamily member 14 [OR (CI) = 1.05 (1.00-1.10); p = 0.036842)], were positively correlated with AD. Additionally, six circulating inflammatory proteins were negatively correlated with AD: the T-cell surface glycoprotein CD5 [OR (CI) = 0.89 (0.84-0.95); p = 0.000191)], macrophage colony-stimulating factor 1 [OR (CI) = 0.93 (0.88-0.99); p = 0.031422)], fractalkine [OR (CI) = 0.91 (0.85-0.97); p = 0.003067)], interleukin-24 [OR (CI) = 0.91 (0.83-0.99); p = 0.031673)], signaling lymphocytic activation molecule [OR(CI) = 0.94 (0.89-1.00); p = 0.039818)], and urokinase-type plasminogen activator [OR(CI) = 0.95 (0.90-1.00); p = 0.037037)].
CONCLUSION
This study confirms the potential causal relationship between circulating inflammatory proteins and AD and provides guidance for the clinical diagnosis and treatment of AD.
背景
特应性皮炎（AD）是一种在临床实践中发生的难治性疾病。作为最常见的炎症性皮肤病之一，其发生和发展与炎症有关。然而，循环炎症蛋白与 AD 之间的确切关系性质仍不确定。
方法
使用 FinnGen 联盟的全基因组关联研究（GWAS）汇总统计数据，通过两样本 MR 分析确定 91 种循环炎症蛋白表达与 AD 之间的因果关系。通过敏感性分析评估 MR 结果的稳健性。
结果
反向方差加权（IVW）方法证实了九种特定循环炎症蛋白表达与 AD 之间的因果关系。研究结果表明，三种循环炎症蛋白，即白细胞介素-18 受体 1 [比值比（CI）=1.08（1.05-1.11）；p=0.000001)]、白细胞介素-8 [比值比（CI）=1.07（1.00-1.14）；p=0.036244)]和肿瘤坏死因子配体超家族成员 14 [比值比（CI）=1.05（1.00-1.10）；p=0.036842)]，与 AD 呈正相关。此外，六种循环炎症蛋白与 AD 呈负相关：T 细胞表面糖蛋白 CD5 [比值比（CI）=0.89（0.84-0.95）；p=0.000191)]、巨噬细胞集落刺激因子 1 [比值比（CI）=0.93（0.88-0.99）；p=0.031422)]、 fractalkine [比值比（CI）=0.91（0.85-0.97）；p=0.003067)]、白细胞介素-24 [比值比（CI）=0.91（0.83-0.99）；p=0.031673)]、信号淋巴细胞激活分子 [比值比（CI）=0.94（0.89-1.00）；p=0.039818)]和尿激酶型纤溶酶原激活物 [比值比（CI）=0.95（0.90-1.00）；p=0.037037)]。
结论
本研究证实了循环炎症蛋白与 AD 之间存在潜在的因果关系，为 AD 的临床诊断和治疗提供了指导。
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