ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Association Between SQSTM1 Dysregulation and Risk in Alopecia Areata: A Mendelian Randomization Study
Provisionally accepted
- The Third People's Hospital of Hangzhou, Hangzhou, China
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Background: Alopecia areata (AA) is an autoimmune disease typified by nonscarring hair loss. It manifests as a heterogeneous disorder with diverse clinical presentations and variable treatment responses, underscoring the significance of identifying novel biomarkers for precision management. Objective: This study aims to explore the relationship between metabolic reprogramming-related genes (MRRGs) and the risk of developing AA. Methods: MRRGs were identified through the GeneCards database and existing literature. Genetic instruments were obtained from the eQTLGen database, and AA-related data were retrieved from the OpenGWAS database. The TwoSampleMR R package was applied for statistical analysis. Additionally, RT-qPCR and immunofluorescence assays were performed to validate the expression of target genes in AA-affected hair follicles and healthy controls. Results: Six MRRGs (DLD, NFE2L2, SDHB, SLC2A1, PSAT1, and SQSTM1) showed significant causal associations with AA. RT-qPCR analysis revealed markedly elevated SQSTM1 mRNA levels in AA-affected hair follicles compared with healthy controls. Immunofluorescence confirmed increased SQSTM1 protein accumulation alongside reduced LC3B-II expression in AA-affected hair follicles. Conclusions: This study underscores the significant association between SQSTM1 and AA, advancing our understanding of AA pathophysiology.
Keywords: Alopecia Areata, Autoimmunity, Autophagy, Inflammation, metabolic reprogramming, Sqstm1
Received: 23 Jun 2025; Accepted: 07 Nov 2025.
Copyright: © 2025 Hu, Wan and Song. 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: Xiuzu Song, songxiuzu@sina.com.cn
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