Genetic support for the causal association between 91 circulating inflammatory proteins and atopic dermatitis: A two-sample Mendelian randomization trial.

IF 2 4区医学 Q3 DERMATOLOGY Skin Research and Technology Pub Date : 2024-08-01 DOI:10.1111/srt.13872

Xinran Du, Hongshuo Shi, Xin Liu, Yi Wang, Ting Du, Peiyao Wang, Linyan Cheng, Jianyong Zhu, Fulun Li

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Abstract

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.

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91 种循环炎症蛋白与特应性皮炎之间因果关系的遗传学支持：双样本孟德尔随机试验。

背景：特应性皮炎（AD特应性皮炎（AD）是临床上常见的难治性疾病。特应性皮炎是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，循环炎症蛋白与特应性皮炎之间关系的确切性质仍不确定：方法：利用芬兰基因组联盟（FinnGen consortia）提供的全基因组关联研究（GWAS）汇总统计数据，对91种循环炎症蛋白的表达与AD之间的因果关系进行了双样本MR分析。通过敏感性分析评估了MR结果的稳健性：结果：反方差加权法（IVW）证实了九种特定循环炎症蛋白的表达与AD之间的因果关系。结果表明，三种循环炎症蛋白，即白细胞介素-18 受体 1 [OR (CI) = 1.08 (1.05-1.11); p = 0.000001)]、白细胞介素-8 [OR (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 [OR (CI) = 1.05 (1.00-1.10); p = 0.036842)]与 AD 呈正相关。此外，6 种循环炎症蛋白与 AD 呈负相关：T 细胞表面糖蛋白 CD5 [OR (CI) = 0.89 (0.84-0.95); p = 0.000191)]、巨噬细胞集落刺激因子 1 [OR (CI) = 0.93 (0.88-0.99); p = 0.031422)]、分叉碱 [OR (CI) = 0.91 (0.85-0.97); p = 0.003067)], 白细胞介素-24 [OR (CI) = 0.91 (0.83-0.99); p = 0.031673)], 信号淋巴细胞活化分子 [OR(CI) = 0.94 (0.89-1.00); p = 0.039818)] 和尿激酶型纤溶酶原激活剂 [OR(CI) = 0.95 (0.90-1.00); p = 0.037037)]：本研究证实了循环炎症蛋白与 AD 之间的潜在因果关系，并为 AD 的临床诊断和治疗提供了指导。

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来源期刊

Skin Research and Technology 医学-皮肤病学

CiteScore

3.30

自引率

9.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Skin Research and Technology is a clinically-oriented journal on biophysical methods and imaging techniques and how they are used in dermatology, cosmetology and plastic surgery for noninvasive quantification of skin structure and functions. Papers are invited on the development and validation of methods and their application in the characterization of diseased, abnormal and normal skin. Topics include blood flow, colorimetry, thermography, evaporimetry, epidermal humidity, desquamation, profilometry, skin mechanics, epiluminiscence microscopy, high-frequency ultrasonography, confocal microscopy, digital imaging, image analysis and computerized evaluation and magnetic resonance. Noninvasive biochemical methods (such as lipids, keratin and tissue water) and the instrumental evaluation of cytological and histological samples are also covered. The journal has a wide scope and aims to link scientists, clinical researchers and technicians through original articles, communications, editorials and commentaries, letters, reviews, announcements and news. Contributions should be clear, experimentally sound and novel.