Associations Between Gene Variants of Lipid‐Lowering Drug Targets and Adverse Outcomes After Ischemic Stroke
Background The association of lipid‐lowering drug targets and their gene variants with cardiovascular diseases has been previously clarified. However, the relationship between gene variants of lipid‐lowering drug targets and the adverse prognosis of ischemic stroke patients remains unclear. Methods...
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Wiley
2024-11-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.036544 |
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| author | Lulu Sun Qilu Zhang Mengyao Shi Yang Liu Zhengbao Zhu Jing Zhang Hao Peng Aili Wang Jing Chen Tan Xu Yonghong Zhang Jiang He |
| author_facet | Lulu Sun Qilu Zhang Mengyao Shi Yang Liu Zhengbao Zhu Jing Zhang Hao Peng Aili Wang Jing Chen Tan Xu Yonghong Zhang Jiang He |
| author_sort | Lulu Sun |
| collection | DOAJ |
| description | Background The association of lipid‐lowering drug targets and their gene variants with cardiovascular diseases has been previously clarified. However, the relationship between gene variants of lipid‐lowering drug targets and the adverse prognosis of ischemic stroke patients remains unclear. Methods and Results Multiple single‐nucleotide polymorphisms associated with 6 lipid‐lowering drug targets were genotyped for patients with ischemic stroke. The primary outcome was death or major disability within 2 years after ischemic stroke. Genetic risk score was constructed from significant single‐nucleotide polymorphisms identified via additive models, which was calculated by multiplying the number of risk alleles at each locus by the corresponding beta coefficient and then summing the products. The rs2006760‐C of the HMGCR, rs11206510‐T of PCSK9, and rs1864163‐G and rs9929488‐G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Each additional risk allele was associated with higher odds of adverse outcomes. Genetic risk score was positively associated with the odds of primary outcome (odds ratio [OR], 1.48 [95% CI, 1.15–1.90]; Ptrend = 0.001), major disability (OR, 1.56 [95% CI, 1.16–2.08]; Ptrend = 0.002), death (hazard ratio [HR], 1.58 [95% CI, 1.12–2.25]; Ptrend = 0.011), and the composite outcome of death or cardiovascular events (HR, 1.41 [95% CI, 1.08–1.85]; Ptrend = 0.010) when 2 extreme quartiles were compared. Conclusions rs2006760‐C of HMGCR, rs11206510‐T of PCSK9, and rs1864163‐G and rs9929488‐G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Furthermore, higher GRS was positively related to the odds of poor outcomes in patients with ischemic stroke. Registration: URL: https://www.clinicaltrials.gov; Identifier: NCT01840072. |
| format | Article |
| id | doaj-art-cbcec7fa8d1a429abc70e5788775882e |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
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| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-cbcec7fa8d1a429abc70e5788775882e2024-11-19T12:31:39ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-11-01132210.1161/JAHA.124.036544Associations Between Gene Variants of Lipid‐Lowering Drug Targets and Adverse Outcomes After Ischemic StrokeLulu Sun0Qilu Zhang1Mengyao Shi2Yang Liu3Zhengbao Zhu4Jing Zhang5Hao Peng6Aili Wang7Jing Chen8Tan Xu9Yonghong Zhang10Jiang He11Department of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non‐communicable Diseases Suzhou Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non‐communicable Diseases Suzhou Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non‐communicable Diseases Suzhou Medical College of Soochow University Suzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non‐communicable Diseases Suzhou Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non‐communicable Diseases Suzhou Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non‐communicable Diseases Suzhou Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non‐communicable Diseases Suzhou Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology Tulane University School of Public Health and Tropical Medicine New Orleans LADepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non‐communicable Diseases Suzhou Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non‐communicable Diseases Suzhou Medical College of Soochow University Suzhou ChinaDepartment of Epidemiology Tulane University School of Public Health and Tropical Medicine New Orleans LABackground The association of lipid‐lowering drug targets and their gene variants with cardiovascular diseases has been previously clarified. However, the relationship between gene variants of lipid‐lowering drug targets and the adverse prognosis of ischemic stroke patients remains unclear. Methods and Results Multiple single‐nucleotide polymorphisms associated with 6 lipid‐lowering drug targets were genotyped for patients with ischemic stroke. The primary outcome was death or major disability within 2 years after ischemic stroke. Genetic risk score was constructed from significant single‐nucleotide polymorphisms identified via additive models, which was calculated by multiplying the number of risk alleles at each locus by the corresponding beta coefficient and then summing the products. The rs2006760‐C of the HMGCR, rs11206510‐T of PCSK9, and rs1864163‐G and rs9929488‐G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Each additional risk allele was associated with higher odds of adverse outcomes. Genetic risk score was positively associated with the odds of primary outcome (odds ratio [OR], 1.48 [95% CI, 1.15–1.90]; Ptrend = 0.001), major disability (OR, 1.56 [95% CI, 1.16–2.08]; Ptrend = 0.002), death (hazard ratio [HR], 1.58 [95% CI, 1.12–2.25]; Ptrend = 0.011), and the composite outcome of death or cardiovascular events (HR, 1.41 [95% CI, 1.08–1.85]; Ptrend = 0.010) when 2 extreme quartiles were compared. Conclusions rs2006760‐C of HMGCR, rs11206510‐T of PCSK9, and rs1864163‐G and rs9929488‐G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Furthermore, higher GRS was positively related to the odds of poor outcomes in patients with ischemic stroke. Registration: URL: https://www.clinicaltrials.gov; Identifier: NCT01840072.https://www.ahajournals.org/doi/10.1161/JAHA.124.036544genetic risk scoreischemic strokelipid‐lowering drug targetsprognosticssingle‐nucleotide polymorphisms |
| spellingShingle | Lulu Sun Qilu Zhang Mengyao Shi Yang Liu Zhengbao Zhu Jing Zhang Hao Peng Aili Wang Jing Chen Tan Xu Yonghong Zhang Jiang He Associations Between Gene Variants of Lipid‐Lowering Drug Targets and Adverse Outcomes After Ischemic Stroke Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease genetic risk score ischemic stroke lipid‐lowering drug targets prognostics single‐nucleotide polymorphisms |
| title | Associations Between Gene Variants of Lipid‐Lowering Drug Targets and Adverse Outcomes After Ischemic Stroke |
| title_full | Associations Between Gene Variants of Lipid‐Lowering Drug Targets and Adverse Outcomes After Ischemic Stroke |
| title_fullStr | Associations Between Gene Variants of Lipid‐Lowering Drug Targets and Adverse Outcomes After Ischemic Stroke |
| title_full_unstemmed | Associations Between Gene Variants of Lipid‐Lowering Drug Targets and Adverse Outcomes After Ischemic Stroke |
| title_short | Associations Between Gene Variants of Lipid‐Lowering Drug Targets and Adverse Outcomes After Ischemic Stroke |
| title_sort | associations between gene variants of lipid lowering drug targets and adverse outcomes after ischemic stroke |
| topic | genetic risk score ischemic stroke lipid‐lowering drug targets prognostics single‐nucleotide polymorphisms |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.036544 |
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