RGMA gene polymorphisms as predictive biomarkers for early relapse in neuromyelitis optica spectrum disorders

Objectives: To explore the potential of RGMA gene polymorphisms as novel biomarkers for predicting disease activity in NMOSD. Methods: We enrolled 117 NMOSD patients and 100 healthy controls. Single nucleotide polymorphism genotyping for the RGMA gene was performed using Sanger sequencing. Associati...

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Main Authors: Xiaoyi Yang, Lei Cui, Jinsong Jiao, Yeqiong Zhang, Renbin Wang, Dantao Peng, Weihe Zhang
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Neurobiology of Disease
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Online Access:http://www.sciencedirect.com/science/article/pii/S0969996125002797
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author Xiaoyi Yang
Lei Cui
Jinsong Jiao
Yeqiong Zhang
Renbin Wang
Dantao Peng
Weihe Zhang
author_facet Xiaoyi Yang
Lei Cui
Jinsong Jiao
Yeqiong Zhang
Renbin Wang
Dantao Peng
Weihe Zhang
author_sort Xiaoyi Yang
collection DOAJ
description Objectives: To explore the potential of RGMA gene polymorphisms as novel biomarkers for predicting disease activity in NMOSD. Methods: We enrolled 117 NMOSD patients and 100 healthy controls. Single nucleotide polymorphism genotyping for the RGMA gene was performed using Sanger sequencing. Associations between RGMA gene polymorphisms and clinical and imaging characteristics, and immune cell activation were analyzed. Results: Carriers of the rs725458-CC and rs4778099-AA genotypes experienced significantly earlier first relapses, but subsequently showed a lower relapse rate. The rs4778099-GG genotype was associated with a higher rate of AQP4-IgG seronegativity, while the rs4778099-AA genotype correlated with a higher likelihood of presenting circumventricular organ syndrome at onset. Carriers of the rs725458-TT genotype were more prone to longer spinal lesion spans. Elevated levels of CD3+T lymphocytes were observed in carriers of the rs725458-TT and rs4778099-GG genotypes during acute phases. Survival analysis revealed that the CC/AA genotypes were linked to earlier relapse, supported by Cox multivariate analysis which identified these genotypes, along with age of onset and onset symptoms, as key predictors of early relapse. Conclusion: RGMA gene polymorphisms, specifically rs725458-CC and rs4778099-AA, are key predictors of early NMOSD relapse. Integrating these markers with clinical data improves relapse risk prediction, enabling more targeted treatment strategies.
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spelling doaj-art-d5d3e3f46da044dfad31b8ba50b443e12025-08-24T05:11:31ZengElsevierNeurobiology of Disease1095-953X2025-10-0121510706310.1016/j.nbd.2025.107063RGMA gene polymorphisms as predictive biomarkers for early relapse in neuromyelitis optica spectrum disordersXiaoyi Yang0Lei Cui1Jinsong Jiao2Yeqiong Zhang3Renbin Wang4Dantao Peng5Weihe Zhang6Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China; Department of Neurology, China-Japan Friendship Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing 100029, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing 100029, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing 100029, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing 100029, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing 100029, China; Corresponding authors at: Department of Neurology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Hepingli, Beijing 100029, China.Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China; Corresponding authors at: Department of Neurology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Hepingli, Beijing 100029, China.Objectives: To explore the potential of RGMA gene polymorphisms as novel biomarkers for predicting disease activity in NMOSD. Methods: We enrolled 117 NMOSD patients and 100 healthy controls. Single nucleotide polymorphism genotyping for the RGMA gene was performed using Sanger sequencing. Associations between RGMA gene polymorphisms and clinical and imaging characteristics, and immune cell activation were analyzed. Results: Carriers of the rs725458-CC and rs4778099-AA genotypes experienced significantly earlier first relapses, but subsequently showed a lower relapse rate. The rs4778099-GG genotype was associated with a higher rate of AQP4-IgG seronegativity, while the rs4778099-AA genotype correlated with a higher likelihood of presenting circumventricular organ syndrome at onset. Carriers of the rs725458-TT genotype were more prone to longer spinal lesion spans. Elevated levels of CD3+T lymphocytes were observed in carriers of the rs725458-TT and rs4778099-GG genotypes during acute phases. Survival analysis revealed that the CC/AA genotypes were linked to earlier relapse, supported by Cox multivariate analysis which identified these genotypes, along with age of onset and onset symptoms, as key predictors of early relapse. Conclusion: RGMA gene polymorphisms, specifically rs725458-CC and rs4778099-AA, are key predictors of early NMOSD relapse. Integrating these markers with clinical data improves relapse risk prediction, enabling more targeted treatment strategies.http://www.sciencedirect.com/science/article/pii/S0969996125002797Neuromyelitis optica spectrum disordersRepulsive guidance molecule a (RGMa)Gene polymorphismsPredictive biomarkerRelapse risk
spellingShingle Xiaoyi Yang
Lei Cui
Jinsong Jiao
Yeqiong Zhang
Renbin Wang
Dantao Peng
Weihe Zhang
RGMA gene polymorphisms as predictive biomarkers for early relapse in neuromyelitis optica spectrum disorders
Neurobiology of Disease
Neuromyelitis optica spectrum disorders
Repulsive guidance molecule a (RGMa)
Gene polymorphisms
Predictive biomarker
Relapse risk
title RGMA gene polymorphisms as predictive biomarkers for early relapse in neuromyelitis optica spectrum disorders
title_full RGMA gene polymorphisms as predictive biomarkers for early relapse in neuromyelitis optica spectrum disorders
title_fullStr RGMA gene polymorphisms as predictive biomarkers for early relapse in neuromyelitis optica spectrum disorders
title_full_unstemmed RGMA gene polymorphisms as predictive biomarkers for early relapse in neuromyelitis optica spectrum disorders
title_short RGMA gene polymorphisms as predictive biomarkers for early relapse in neuromyelitis optica spectrum disorders
title_sort rgma gene polymorphisms as predictive biomarkers for early relapse in neuromyelitis optica spectrum disorders
topic Neuromyelitis optica spectrum disorders
Repulsive guidance molecule a (RGMa)
Gene polymorphisms
Predictive biomarker
Relapse risk
url http://www.sciencedirect.com/science/article/pii/S0969996125002797
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