Metabolic biomarkers mediate allergic rhinitis via circulating inflammatory proteins: Evidence from a Mendelian randomization study

Objective: Allergic Rhinitis (AR), a prevalent allergic condition, markedly diminishes quality of life and increases public health burdens. This study investigated the mediating roles of Metabolic Biomarkers (MBs) in the associations between Circulating Inflammatory Proteins (CIPs) and AR, aiming to...

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Main Authors: Xiang Cao, Boyang Zhang, Wei Wang, Zijiao Xu, Zhixin Jiang
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Brazilian Journal of Otorhinolaryngology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1808869425001016
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author Xiang Cao
Boyang Zhang
Wei Wang
Zijiao Xu
Zhixin Jiang
author_facet Xiang Cao
Boyang Zhang
Wei Wang
Zijiao Xu
Zhixin Jiang
author_sort Xiang Cao
collection DOAJ
description Objective: Allergic Rhinitis (AR), a prevalent allergic condition, markedly diminishes quality of life and increases public health burdens. This study investigated the mediating roles of Metabolic Biomarkers (MBs) in the associations between Circulating Inflammatory Proteins (CIPs) and AR, aiming to uncover novel therapeutic targets. Methods: Utilizing Mendelian Randomization (MR), we leveraged genetic variants as instrumental variables to delineate causal relationships between CIPs and AR. Data were extracted from comprehensive Genome-Wide Association Studies (GWAS). A two-sample MR approach was employed to assess both the direct and mediated effects of CIPs on AR through MBs. Inverse-Variance Weighting (IVW) served as the main analytical method, supplemented by rigorous sensitivity analyses to confirm the robustness of the findings. Results: Our analysis revealed that specific CIPs like C-C motif Chemokine-19 (CCL19), Notch-like Epidermal growth factor-related Receptor (DNER), and Interleukin-6 (IL-6) significantly elevate the risk of AR, whereas Interleukin-10 (IL-10) exhibit protective properties. Key MBs, notably Adenosine 5'-Monophosphate (AMP) to urate ratio, plasma lactate, and N-acetylputrescine, played critical roles in mediating these relationships, indicating their potential as therapeutic targets. Conclusion: This investigation highlights the pivotal role of MBs in modulating the influence of CIPs on AR. The insights gained from this study not only deepen our understanding of AR pathophysiology but also open new avenues for metabolic intervention in its treatment. Level of evidence: In terms of level of evidence, MR studies are second only to randomized controlled trials.
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spelling doaj-art-599c19fb1d704caf8523c0b5b712facb2025-08-20T03:28:05ZengElsevierBrazilian Journal of Otorhinolaryngology1808-86942025-09-0191510165810.1016/j.bjorl.2025.101658Metabolic biomarkers mediate allergic rhinitis via circulating inflammatory proteins: Evidence from a Mendelian randomization studyXiang Cao0Boyang Zhang1Wei Wang2Zijiao Xu3Zhixin Jiang4Jiangsu University, Affiliated People’s Hospital, Department of Ophthalmology, Zhenjiang, Jiangsu, China; Zhenjiang Kangfu Eye Hospital, Zhenjiang, Jiangsu, ChinaClinical College of Ophthalmology, Tianjin Medical University, Tianjin, China; Tianjin Eye Hospital, Nankai University Affiliated Eye Hospital, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, ChinaTianjin Eye Hospital, Nankai University Affiliated Eye Hospital, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, China; Shanxi Medical University, Shanxi, ChinaTianjin Eye Hospital, Nankai University Affiliated Eye Hospital, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, ChinaTianjin Eye Hospital, Nankai University Affiliated Eye Hospital, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin, China; Corresponding author.Objective: Allergic Rhinitis (AR), a prevalent allergic condition, markedly diminishes quality of life and increases public health burdens. This study investigated the mediating roles of Metabolic Biomarkers (MBs) in the associations between Circulating Inflammatory Proteins (CIPs) and AR, aiming to uncover novel therapeutic targets. Methods: Utilizing Mendelian Randomization (MR), we leveraged genetic variants as instrumental variables to delineate causal relationships between CIPs and AR. Data were extracted from comprehensive Genome-Wide Association Studies (GWAS). A two-sample MR approach was employed to assess both the direct and mediated effects of CIPs on AR through MBs. Inverse-Variance Weighting (IVW) served as the main analytical method, supplemented by rigorous sensitivity analyses to confirm the robustness of the findings. Results: Our analysis revealed that specific CIPs like C-C motif Chemokine-19 (CCL19), Notch-like Epidermal growth factor-related Receptor (DNER), and Interleukin-6 (IL-6) significantly elevate the risk of AR, whereas Interleukin-10 (IL-10) exhibit protective properties. Key MBs, notably Adenosine 5'-Monophosphate (AMP) to urate ratio, plasma lactate, and N-acetylputrescine, played critical roles in mediating these relationships, indicating their potential as therapeutic targets. Conclusion: This investigation highlights the pivotal role of MBs in modulating the influence of CIPs on AR. The insights gained from this study not only deepen our understanding of AR pathophysiology but also open new avenues for metabolic intervention in its treatment. Level of evidence: In terms of level of evidence, MR studies are second only to randomized controlled trials.http://www.sciencedirect.com/science/article/pii/S1808869425001016Allergic rhinitisMendelian randomizationMetabolic biomarkersCirculating inflammatory proteins
spellingShingle Xiang Cao
Boyang Zhang
Wei Wang
Zijiao Xu
Zhixin Jiang
Metabolic biomarkers mediate allergic rhinitis via circulating inflammatory proteins: Evidence from a Mendelian randomization study
Brazilian Journal of Otorhinolaryngology
Allergic rhinitis
Mendelian randomization
Metabolic biomarkers
Circulating inflammatory proteins
title Metabolic biomarkers mediate allergic rhinitis via circulating inflammatory proteins: Evidence from a Mendelian randomization study
title_full Metabolic biomarkers mediate allergic rhinitis via circulating inflammatory proteins: Evidence from a Mendelian randomization study
title_fullStr Metabolic biomarkers mediate allergic rhinitis via circulating inflammatory proteins: Evidence from a Mendelian randomization study
title_full_unstemmed Metabolic biomarkers mediate allergic rhinitis via circulating inflammatory proteins: Evidence from a Mendelian randomization study
title_short Metabolic biomarkers mediate allergic rhinitis via circulating inflammatory proteins: Evidence from a Mendelian randomization study
title_sort metabolic biomarkers mediate allergic rhinitis via circulating inflammatory proteins evidence from a mendelian randomization study
topic Allergic rhinitis
Mendelian randomization
Metabolic biomarkers
Circulating inflammatory proteins
url http://www.sciencedirect.com/science/article/pii/S1808869425001016
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AT weiwang metabolicbiomarkersmediateallergicrhinitisviacirculatinginflammatoryproteinsevidencefromamendelianrandomizationstudy
AT zijiaoxu metabolicbiomarkersmediateallergicrhinitisviacirculatinginflammatoryproteinsevidencefromamendelianrandomizationstudy
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