血清细胞因子与肩周炎风险之间的遗传学关联:双向泯灭随机研究

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
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引用次数: 0

摘要

背景尽管现有研究表明慢性低度炎症与肩周炎(FS)发病之间存在联系,但不同的循环炎症因子与肩周炎之间的确切因果关系尚未得到彻底评估。在这项研究中,我们采用了双向双样本孟德尔随机化(MR)分析法来研究系统性细胞因子与肩周炎之间的潜在因果关系。研究利用了一个全基因组关联数据集,其中包括来自 8293 名芬兰后裔的 41 种血清细胞因子,以及来自英国生物库(UK Biobank)的肩周炎数据,其中包括 10104 例肩周炎病例和 451099 例对照。主要的 MR 方法是反方差加权法,另外还采用了四种 MR 技术(MR-Egger、加权中位数、简单模式和加权模式)来支持和验证研究结果。使用 Cochrane's Q 和 MR-Egger 截距检验对异质性和水平多向性进行了评估。此外,还进行了一系列敏感性分析,以加强这些研究结果的准确性和可信度。结果基于 IVW 方法,遗传预测生长调控癌基因 alpha (GROa) 水平的增加(OR=1.08,95 % CI 1.02-1.13,P=0.005)。13,P=0.005)、干扰素γ诱导蛋白10(IP-10)(OR=1.09,95 % CI 1.02-1.17,P=0.010)、激活时调节的C-C Motif趋化因子配体5(CCL5)(OR=1.11,95 % CI 1.03-1.20,P=0.007)水平的增加与FS风险的增加呈提示性相关。反向 MR 分析显示,FS 对 41 种全身炎症因子没有明显的因果关系。结论本研究确定了 41 个全身炎症因子与 FS 之间的因果关系,表明 GROa、IP-10 和 CCL5 水平升高与 FS 风险升高有关。我们有必要进一步研究这些生物标志物作为 FS 早期预测指标和治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genetic insights into the association between serum cytokines and frozen shoulder risk: A bidirectional mendelian randomization study

Background

Although existing studies have indicated a connection between chronic low-grade inflammation and the onset of frozen shoulder (FS), the precise causal relationship between distinct circulating inflammatory factors and FS has yet to be thoroughly evaluated. In this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between systemic cytokines and FS.

Methods

A genome-wide association dataset comprising 41 serum cytokines from 8,293 individuals of Finnish descent was utilized, along with FS data from the UK Biobank included 10,104 FS cases and 451,099 controls. The primary MR method was the inverse variance weighted approach, and four additional MR techniques (MR-Egger, weighted median, simple mode, and weighted mode) were also employed to support and validate the findings. Heterogeneity and horizontal pleiotropy assessments were assessed using Cochrane’s Q and MR-Egger intercept tests. Moreover, a series of sensitivity analyses were conducted to strengthen the accuracy and credibility of these findings.

Results

Based on the IVW method, genetically predicted increasing levels of growth regulated oncogene alpha (GROa) (OR=1.08, 95 % CI 1.02–1.13, P=0.005), interferon gamma-induced protein 10 (IP-10) (OR=1.09, 95 % CI 1.02–1.17, P=0.010), regulated on activation, C–C Motif Chemokine Ligand 5 (CCL5) (OR=1.11, 95 % CI 1.03–1.20, P=0.007) were suggestively associated with an increased risk of FS. Reverse MR analysis revealed no significant causal effect of FS on the 41 systemic inflammatory factors. No heterogeneity or horizontal pleiotropy was observed in our analysis.

Conclusion

This study established a causal association between 41 systemic inflammatory factors and FS, indicating that elevated levels of GROa, IP-10 and CCL5 were associated with a higher risk of FS. Further research is warranted to explore the potential of these biomarkers as early predictors and therapeutic targets for FS.

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来源期刊
Cytokine
Cytokine 医学-免疫学
CiteScore
7.60
自引率
2.60%
发文量
262
审稿时长
48 days
期刊介绍: The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.
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