Genetically proxied antidiabetic drugs targets and stroke risk
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04565-x |
| _version_ | 1797451679346458624 |
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| author | Yahui Zhu Mao Li Hongfen Wang Fei Yang Xinyuan Pang Rongrong Du Jinghong Zhang Xusheng Huang |
| author_facet | Yahui Zhu Mao Li Hongfen Wang Fei Yang Xinyuan Pang Rongrong Du Jinghong Zhang Xusheng Huang |
| author_sort | Yahui Zhu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T14:58:00Z |
| format | Article |
| id | doaj.art-454eb2ce52994d02a920bb22473d78e8 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-09T14:58:00Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-454eb2ce52994d02a920bb22473d78e82023-11-26T14:05:14ZengBMCJournal of Translational Medicine1479-58762023-09-0121111510.1186/s12967-023-04565-xGenetically proxied antidiabetic drugs targets and stroke riskYahui Zhu0Mao Li1Hongfen Wang2Fei Yang3Xinyuan Pang4Rongrong Du5Jinghong Zhang6Xusheng Huang7Medical School of Chinese PLADepartment of Neurology, The First Medical Center, Chinese PLA General HospitalDepartment of Neurology, The First Medical Center, Chinese PLA General HospitalDepartment of Neurology, The First Medical Center, Chinese PLA General HospitalDepartment of Neurology, The First Medical Center, Chinese PLA General HospitalDepartment of Neurology, The First Medical Center, Chinese PLA General HospitalMedical School of Chinese PLAMedical School of Chinese PLAAbstract 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.https://doi.org/10.1186/s12967-023-04565-xAntidiabetic drugsStrokeMendelian randomizationSulfonylurea |
| spellingShingle | Yahui Zhu Mao Li Hongfen Wang Fei Yang Xinyuan Pang Rongrong Du Jinghong Zhang Xusheng Huang Genetically proxied antidiabetic drugs targets and stroke risk Journal of Translational Medicine Antidiabetic drugs Stroke Mendelian randomization Sulfonylurea |
| 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 | Antidiabetic drugs Stroke Mendelian randomization Sulfonylurea |
| url | https://doi.org/10.1186/s12967-023-04565-x |
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