Association of MTMR3 rs12537 at miR-181a Binding Site with Ischemic Stroke in Southern Chinese Han Population
Linfa Chen,1,2,* Shan Wei,2,* Yutian Zhang,3,* You Li,3 Zishan Li,2 Pengru Huang,1 Chun Xiao,2 Yusheng Zhang1 1Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 2Huizhou Third People’s Hospit...
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Dove Medical Press
2025-05-01
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| author | Chen L Wei S Zhang Y Li Y Li Z Huang P Xiao C Zhang Y |
| author_facet | Chen L Wei S Zhang Y Li Y Li Z Huang P Xiao C Zhang Y |
| author_sort | Chen L |
| collection | DOAJ |
| description | Linfa Chen,1,2,* Shan Wei,2,* Yutian Zhang,3,* You Li,3 Zishan Li,2 Pengru Huang,1 Chun Xiao,2 Yusheng Zhang1 1Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 2Huizhou Third People’s Hospital, Guangzhou Medical University, Huizhou, 516002, People’s Republic of China; 3Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yusheng Zhang, Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China, Email zhangys@jnu.edu.cn Chun Xiao, Huizhou Third People’s Hospital, Guangzhou Medical University, Huizhou, 516002, People’s Republic of China, Email HuizhouXiaoc@163.comBackground: Single nucleotide polymorphisms (SNPs) at microRNA (miRNA)--binding sites influence the development of ischemic stroke (IS) by affecting the expression of specific target genes. Myotubularin-related protein 3 (MTMR3), which is involved in autophagy, is directly targeted by miR-181a. This research examined the potential association between the SNP rs12537 in the miRNA-181a binding location within the 3′ untranslated region (3′-UTR) of MTMR3 and the incidence and prognosis of IS.Methods: An improved multitemperature ligase detection reaction assay was used to perform genotyping analysis in two independent case-control datasets consisting of 1128 subjects with IS and 1140 healthy controls with matched ages.Results: The distribution frequencies of the T allele (p = 5.2× 10− 4) of SNP rs12537 in MTMR3 were elevated significantly in IS patients as compared to healthy controls. Further categorization based on IS subtypes revealed that individuals carrying the variation T allele were linked with a higher risk of suffering large-artery (p = 1.2× 10− 3) and small-artery (p = 7.0× 10− 4) atherosclerotic stroke subtypes. The T allele of rs12537 was shown to be linked to both moderate and severe stroke (NIHSS ≥ 6) (p = 0.011), as well as a poor short-term outcome (p = 0.016) of IS. A significant correlation was also found between the rs12537 T allele mutation and a decrease in MTMR3 (p = 0.019), as well as an elevated miR-181a (p = 0.021) and LC3B (p = 0.026) in individuals with IS.Conclusion: This study identified a novel role for the rs12537 variant in influencing IS susceptibility and prognosis, potentially by modulating MTMR3 expression and leading to increased autophagy.Keywords: ischemic stroke, MTMR3, polymorphism, risk, prognosis |
| format | Article |
| id | doaj-art-897c8b234a4a44a19da4881146898d52 |
| institution | DOAJ |
| issn | 1178-7074 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Dove Medical Press |
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| series | International Journal of General Medicine |
| spelling | doaj-art-897c8b234a4a44a19da4881146898d522025-08-20T03:23:59ZengDove Medical PressInternational Journal of General Medicine1178-70742025-05-01Volume 18Issue 126592672103193Association of MTMR3 rs12537 at miR-181a Binding Site with Ischemic Stroke in Southern Chinese Han PopulationChen L0Wei SZhang YLi Y1Li Z2Huang PXiao C3Zhang Y4NeurologyGuangdong Key Laboratory of Age-Related Cardiac and Cerebral DiseasesCentral laboratoryCardiologyNeurologyLinfa Chen,1,2,* Shan Wei,2,* Yutian Zhang,3,* You Li,3 Zishan Li,2 Pengru Huang,1 Chun Xiao,2 Yusheng Zhang1 1Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 2Huizhou Third People’s Hospital, Guangzhou Medical University, Huizhou, 516002, People’s Republic of China; 3Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yusheng Zhang, Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China, Email zhangys@jnu.edu.cn Chun Xiao, Huizhou Third People’s Hospital, Guangzhou Medical University, Huizhou, 516002, People’s Republic of China, Email HuizhouXiaoc@163.comBackground: Single nucleotide polymorphisms (SNPs) at microRNA (miRNA)--binding sites influence the development of ischemic stroke (IS) by affecting the expression of specific target genes. Myotubularin-related protein 3 (MTMR3), which is involved in autophagy, is directly targeted by miR-181a. This research examined the potential association between the SNP rs12537 in the miRNA-181a binding location within the 3′ untranslated region (3′-UTR) of MTMR3 and the incidence and prognosis of IS.Methods: An improved multitemperature ligase detection reaction assay was used to perform genotyping analysis in two independent case-control datasets consisting of 1128 subjects with IS and 1140 healthy controls with matched ages.Results: The distribution frequencies of the T allele (p = 5.2× 10− 4) of SNP rs12537 in MTMR3 were elevated significantly in IS patients as compared to healthy controls. Further categorization based on IS subtypes revealed that individuals carrying the variation T allele were linked with a higher risk of suffering large-artery (p = 1.2× 10− 3) and small-artery (p = 7.0× 10− 4) atherosclerotic stroke subtypes. The T allele of rs12537 was shown to be linked to both moderate and severe stroke (NIHSS ≥ 6) (p = 0.011), as well as a poor short-term outcome (p = 0.016) of IS. A significant correlation was also found between the rs12537 T allele mutation and a decrease in MTMR3 (p = 0.019), as well as an elevated miR-181a (p = 0.021) and LC3B (p = 0.026) in individuals with IS.Conclusion: This study identified a novel role for the rs12537 variant in influencing IS susceptibility and prognosis, potentially by modulating MTMR3 expression and leading to increased autophagy.Keywords: ischemic stroke, MTMR3, polymorphism, risk, prognosishttps://www.dovepress.com/association-of-mtmr3-rs12537-at-mir-181a-binding-site-with-ischemic-st-peer-reviewed-fulltext-article-IJGMischemic strokeMTMR3polymorphismriskprognosis |
| spellingShingle | Chen L Wei S Zhang Y Li Y Li Z Huang P Xiao C Zhang Y Association of MTMR3 rs12537 at miR-181a Binding Site with Ischemic Stroke in Southern Chinese Han Population International Journal of General Medicine ischemic stroke MTMR3 polymorphism risk prognosis |
| title | Association of MTMR3 rs12537 at miR-181a Binding Site with Ischemic Stroke in Southern Chinese Han Population |
| title_full | Association of MTMR3 rs12537 at miR-181a Binding Site with Ischemic Stroke in Southern Chinese Han Population |
| title_fullStr | Association of MTMR3 rs12537 at miR-181a Binding Site with Ischemic Stroke in Southern Chinese Han Population |
| title_full_unstemmed | Association of MTMR3 rs12537 at miR-181a Binding Site with Ischemic Stroke in Southern Chinese Han Population |
| title_short | Association of MTMR3 rs12537 at miR-181a Binding Site with Ischemic Stroke in Southern Chinese Han Population |
| title_sort | association of mtmr3 rs12537 at mir 181a binding site with ischemic stroke in southern chinese han population |
| topic | ischemic stroke MTMR3 polymorphism risk prognosis |
| url | https://www.dovepress.com/association-of-mtmr3-rs12537-at-mir-181a-binding-site-with-ischemic-st-peer-reviewed-fulltext-article-IJGM |
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