Circulating inflammatory cytokines and risk of aortic stenosis: A Mendelian randomization analysis

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-02-21 DOI:10.1016/j.cyto.2025.156887

Xiaohan Qiu , Jijun Wu , Zehao Chen , Yu Zhang , Luying Cao , Ning Wang , Junlin Teng , Cong Su , Congyi Cheng , Fen Wang , Wenqiang Chen

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引用次数: 0

Abstract

Background

Observational studies have consistently reported positive associations between inflammatory biomarkers and the risk of developing aortic stenosis (AS). However, it is crucial to acknowledge that conventional observational studies are prone to various forms of bias, including reverse causation and residual confounding. To delve deeper into unraveling the potential causal relationship between inflammatory biomarkers and aortic stenosis, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis.

Methods

In order to explore the causal effect of exposure to various circulating cytokines on the risk of developing AS, we carefully selected AS datasets as the exposures from the summary statistics of the genome-wide association study (GWAS) conducted by FinnGen. The dataset consisted of a sample size of 3283 for AS cases and 210,463 for controls. To estimate the MR analysis, we primarily adopted the inverse variance weighted (IVW) method. Additionally, we employed complementary methods, including Weighted Median, MR Egger, Weighted Mode, and Simple Mode, to analyze the causal associations comprehensively. In order to assess the presence of heterogeneity, we utilized Cochran's Q statistic and MR-Egger regression. To ensure the robustness and consistency of our findings, we conducted a leave-one-out analysis.

Result

We observed a positive association between interleukin-18 (IL-18) levels and AS (odds ratio [OR] per standard deviation [SD] = 1.080; 95 % confidence interval [CI] 1.024 to 1.139), as well as between interferon-gamma levels (IFN-γ) and AS (OR per SD = 1.157; 95 % CI 1.028 to 1.302). Conversely, we found an inverse association between interleukin-13 (IL-13) levels and AS (OR per SD = 0.942; 95 % CI 0.890 to 0.997), as well as between interleukin-5 (IL-5) levels and AS (OR per SD = 0.892; 95 % CI 0.804 to 0.990).

Conclusion

Our research enhances the current understanding of the role of specific inflammatory biomarker pathways in aortic stenosis. Nevertheless, further validation is required to assess the viability of targeting these cytokines through pharmacological or lifestyle interventions as potential treatments for aortic stenosis.

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来源期刊

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.