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Genetically proxied antidiabetic drugs targets and stroke risk

BACKGROUND: Previous studies have assessed the association between antidiabetic drugs and stroke risk, but the results are inconsistent. Mendelian randomization (MR) was used to assess effects of antidiabetic drugs on stroke risk. METHODS: We selected blood glucose-lowering variants in genes encodin...

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Autores principales: Zhu, Yahui, Li, Mao, Wang, Hongfen, Yang, Fei, Pang, Xinyuan, Du, Rongrong, Zhang, Jinghong, Huang, Xusheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10544120/
https://www.ncbi.nlm.nih.gov/pubmed/37777789
http://dx.doi.org/10.1186/s12967-023-04565-x
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author Zhu, Yahui
Li, Mao
Wang, Hongfen
Yang, Fei
Pang, Xinyuan
Du, Rongrong
Zhang, Jinghong
Huang, Xusheng
author_facet Zhu, Yahui
Li, Mao
Wang, Hongfen
Yang, Fei
Pang, Xinyuan
Du, Rongrong
Zhang, Jinghong
Huang, Xusheng
author_sort Zhu, Yahui
collection PubMed
description BACKGROUND: Previous studies have assessed the association between antidiabetic drugs and stroke risk, but the results are inconsistent. Mendelian randomization (MR) was used to assess effects of antidiabetic drugs on stroke risk. METHODS: We selected blood glucose-lowering variants in genes encoding antidiabetic drugs targets from genome-wide association studies (GWAS). A two-sample MR and Colocalization analyses were applied to examine associations between antidiabetic drugs and the risk of stroke. For antidiabetic agents that had effect on stroke risk, an independent blood glucose GWAS summary data was used for further verification. RESULTS: Genetic proxies for sulfonylureas targets were associated with reduced risk of any stroke (OR=0.062, 95% CI 0.013-0.295, P=4.65×10(-4)) and any ischemic stroke (OR=0.055, 95% CI 0.010-0.289, P=6.25×10(-4)), but not with intracranial hemorrhage. Colocalization supported shared casual variants for blood glucose with any stroke and any ischemic stroke within the encoding genes for sulfonylureas targets (KCNJ11 and ABCC8) (posterior probability>0.7). Furthermore, genetic variants in the targets of insulin/insulin analogues, glucagon-like peptide-1 analogues, thiazolidinediones, and metformin were not associated with the risk of any stroke, any ischemic stroke and intracranial hemorrhage. The association was consistent in the analysis of sulfonylureas with stroke risk using an independent blood glucose GWAS summary data. CONCLUSIONS: Our findings showed that genetic proxies for sulfonylureas targets by lowering blood glucose were associated with a lower risk of any stroke and any ischemic stroke. The study might be of great significance to guide the selection of glucose-lowering drugs in individuals at high risk of stroke. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04565-x.
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spelling pubmed-105441202023-10-03 Genetically proxied antidiabetic drugs targets and stroke risk Zhu, Yahui Li, Mao Wang, Hongfen Yang, Fei Pang, Xinyuan Du, Rongrong Zhang, Jinghong Huang, Xusheng J Transl Med Research BACKGROUND: Previous studies have assessed the association between antidiabetic drugs and stroke risk, but the results are inconsistent. Mendelian randomization (MR) was used to assess effects of antidiabetic drugs on stroke risk. METHODS: We selected blood glucose-lowering variants in genes encoding antidiabetic drugs targets from genome-wide association studies (GWAS). A two-sample MR and Colocalization analyses were applied to examine associations between antidiabetic drugs and the risk of stroke. For antidiabetic agents that had effect on stroke risk, an independent blood glucose GWAS summary data was used for further verification. RESULTS: Genetic proxies for sulfonylureas targets were associated with reduced risk of any stroke (OR=0.062, 95% CI 0.013-0.295, P=4.65×10(-4)) and any ischemic stroke (OR=0.055, 95% CI 0.010-0.289, P=6.25×10(-4)), but not with intracranial hemorrhage. Colocalization supported shared casual variants for blood glucose with any stroke and any ischemic stroke within the encoding genes for sulfonylureas targets (KCNJ11 and ABCC8) (posterior probability>0.7). Furthermore, genetic variants in the targets of insulin/insulin analogues, glucagon-like peptide-1 analogues, thiazolidinediones, and metformin were not associated with the risk of any stroke, any ischemic stroke and intracranial hemorrhage. The association was consistent in the analysis of sulfonylureas with stroke risk using an independent blood glucose GWAS summary data. CONCLUSIONS: Our findings showed that genetic proxies for sulfonylureas targets by lowering blood glucose were associated with a lower risk of any stroke and any ischemic stroke. The study might be of great significance to guide the selection of glucose-lowering drugs in individuals at high risk of stroke. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04565-x. BioMed Central 2023-09-30 /pmc/articles/PMC10544120/ /pubmed/37777789 http://dx.doi.org/10.1186/s12967-023-04565-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhu, Yahui
Li, Mao
Wang, Hongfen
Yang, Fei
Pang, Xinyuan
Du, Rongrong
Zhang, Jinghong
Huang, Xusheng
Genetically proxied antidiabetic drugs targets and stroke risk
title Genetically proxied antidiabetic drugs targets and stroke risk
title_full Genetically proxied antidiabetic drugs targets and stroke risk
title_fullStr Genetically proxied antidiabetic drugs targets and stroke risk
title_full_unstemmed Genetically proxied antidiabetic drugs targets and stroke risk
title_short Genetically proxied antidiabetic drugs targets and stroke risk
title_sort genetically proxied antidiabetic drugs targets and stroke risk
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10544120/
https://www.ncbi.nlm.nih.gov/pubmed/37777789
http://dx.doi.org/10.1186/s12967-023-04565-x
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