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Functional Genetic Variation in the 3′-UTRNTRK2 is Associated with Risk of Ischemic Stroke

BACKGROUND: Stroke is a leading cause of death and disability worldwide. It remains difficult to treat brain injury and improve functional rehabilitation after cerebral ischemia. Brain-derived neurotrophic factor (BDNF) is involved in ischemic stroke (IS) through interactions in the CREB1-BDNF-NTRk2...

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Autores principales: Shi, Jiajia, Sun, Ying, Hua, Jiajia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669521/
https://www.ncbi.nlm.nih.gov/pubmed/33209049
http://dx.doi.org/10.2147/PGPM.S270319
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author Shi, Jiajia
Sun, Ying
Hua, Jiajia
author_facet Shi, Jiajia
Sun, Ying
Hua, Jiajia
author_sort Shi, Jiajia
collection PubMed
description BACKGROUND: Stroke is a leading cause of death and disability worldwide. It remains difficult to treat brain injury and improve functional rehabilitation after cerebral ischemia. Brain-derived neurotrophic factor (BDNF) is involved in ischemic stroke (IS) through interactions in the CREB1-BDNF-NTRk2 pathway. In this study, we aimed to determine the association of NTRK2 gene polymorphisms and the effects of intergenetic interactions in the Chinese population. MATERIALS AND METHODS: A total of 400 patients diagnosed with IS and 400 healthy controls were enrolled for genotyping. Detailed sequence-based analysis was predicted through bioinformatical investigation. Polymorphisms associated with miRNA were analyzed by a dual-luciferase reporter assay system. RESULTS: Analysis of clinical characteristics revealed that IS was highly associated with exposure to cigarette smoking, alcohol intake, as well as metabolic diseases, such as diabetes, hypertension, and higher serum triglyceride concentration. Three polymorphisms in NTRK2 located in the 3ʹ-untranslated region (3ʹ-UTR) were genotyped. Logistic regression analysis showed that IS patients with rs11140793, rs7047042, and rs1221 polymorphisms had a higher risk of stroke and indicated a worse short-term recovery. The mRNA level of NTRK2 was suppressed in a mutant genotype compared with wild genotype. The suppression of NTRK2 was induced by the gain-of-binding ability of certain miRNAs through the direct binding of 3ʹ-UTR. CONCLUSION: Our research indicated that, by influencing the expression of NTRK2, the SNPs rs11140793, rs7047042, and rs1221 in the 3′UTR of NTRK2 can be used as risk factors for IS patients.
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spelling pubmed-76695212020-11-17 Functional Genetic Variation in the 3′-UTRNTRK2 is Associated with Risk of Ischemic Stroke Shi, Jiajia Sun, Ying Hua, Jiajia Pharmgenomics Pers Med Original Research BACKGROUND: Stroke is a leading cause of death and disability worldwide. It remains difficult to treat brain injury and improve functional rehabilitation after cerebral ischemia. Brain-derived neurotrophic factor (BDNF) is involved in ischemic stroke (IS) through interactions in the CREB1-BDNF-NTRk2 pathway. In this study, we aimed to determine the association of NTRK2 gene polymorphisms and the effects of intergenetic interactions in the Chinese population. MATERIALS AND METHODS: A total of 400 patients diagnosed with IS and 400 healthy controls were enrolled for genotyping. Detailed sequence-based analysis was predicted through bioinformatical investigation. Polymorphisms associated with miRNA were analyzed by a dual-luciferase reporter assay system. RESULTS: Analysis of clinical characteristics revealed that IS was highly associated with exposure to cigarette smoking, alcohol intake, as well as metabolic diseases, such as diabetes, hypertension, and higher serum triglyceride concentration. Three polymorphisms in NTRK2 located in the 3ʹ-untranslated region (3ʹ-UTR) were genotyped. Logistic regression analysis showed that IS patients with rs11140793, rs7047042, and rs1221 polymorphisms had a higher risk of stroke and indicated a worse short-term recovery. The mRNA level of NTRK2 was suppressed in a mutant genotype compared with wild genotype. The suppression of NTRK2 was induced by the gain-of-binding ability of certain miRNAs through the direct binding of 3ʹ-UTR. CONCLUSION: Our research indicated that, by influencing the expression of NTRK2, the SNPs rs11140793, rs7047042, and rs1221 in the 3′UTR of NTRK2 can be used as risk factors for IS patients. Dove 2020-11-12 /pmc/articles/PMC7669521/ /pubmed/33209049 http://dx.doi.org/10.2147/PGPM.S270319 Text en © 2020 Shi et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Shi, Jiajia
Sun, Ying
Hua, Jiajia
Functional Genetic Variation in the 3′-UTRNTRK2 is Associated with Risk of Ischemic Stroke
title Functional Genetic Variation in the 3′-UTRNTRK2 is Associated with Risk of Ischemic Stroke
title_full Functional Genetic Variation in the 3′-UTRNTRK2 is Associated with Risk of Ischemic Stroke
title_fullStr Functional Genetic Variation in the 3′-UTRNTRK2 is Associated with Risk of Ischemic Stroke
title_full_unstemmed Functional Genetic Variation in the 3′-UTRNTRK2 is Associated with Risk of Ischemic Stroke
title_short Functional Genetic Variation in the 3′-UTRNTRK2 is Associated with Risk of Ischemic Stroke
title_sort functional genetic variation in the 3′-utrntrk2 is associated with risk of ischemic stroke
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669521/
https://www.ncbi.nlm.nih.gov/pubmed/33209049
http://dx.doi.org/10.2147/PGPM.S270319
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