ORIGINAL RESEARCH article
Front. Med.
Sec. Dermatology
This article is part of the Research TopicType 2 Inflammatory Skin Diseases: Novel Therapies and Clinical InsightsView all 5 articles
Neuromedin B identified as a therapeutic target for atopic dermatitis: Evidence from Mendelian randomization and PCR validation
Provisionally accepted
- 1Shanghai Pudong New Area Gongli Hospital, Shanghai, China
- 2Second Affiliated Hospital of Soochow University, Suzhou, China
- 3The First Affiliated Hospital of Soochow University, Suzhou, China
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Introduction: Atopic dermatitis (AD) is a long-standing inflammatory dermatosis marked by intense itching and immune imbalance. Despite recent advances in targeted biologic therapies, limitations in efficacy and cost highlight the urgent need for novel therapeutic targets. Methods: We employed Mendelian randomization (MR) by combining genome-wide association studies (GWAS), expression quantitative trait loci (eQTL), and protein QTL (pQTL) datasets to identify causal druggable genes associated with AD. To enhance the validity of causal inference, we further utilized colocalization and summary-data-based MR (SMR) techniques. We validated the expression of five prioritized genes using reverse transcription quantitative PCR (RT-qPCR), performed on RNA extracted from the peripheral blood of AD patients and healthy controls Results: The MR approach revealed 32 candidate genes with potential druggable properties linked to AD, with 12 showing strong colocalization signals (posterior probability of hypothesis 4 (PP.H4) > 0.8). The pQTL analysis indicated that increased plasma NMB levels were associated with a heightened risk of AD (OR=1.18, P=3.29×10^-8), a conclusion further corroborated by SMR analysis. RT-qPCR confirmed significantly elevated expression of NMB, IL2RA, IL1RL1, and PRKCQ in the peripheral blood samples of AD patients. Additionally, MR studies demonstrated that NMB was associated with bullous pemphigoid and urticaria. Conclusion: Integrative MR and PCR validation across Icelandic, Finnish and Chinese samples nominates NMB as a candidate AD target. These preliminary, multi-ancestry signals now require replication in large, population-matched cohorts before any therapeutic translation.
Keywords: atopic dermatitis, Mendelian randomization, neuromedin B, Pruritus, RT-qPCR, Druggable genes
Received: 05 Jul 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Zhang, Yao, Ke, Bu, Jiao and Ji. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qingqing Jiao, qingqingjiao@suda.edu.cn
Jiang Ji, jijiang@suda.edu.cn
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