Pharmacogenetics polygenic response score predicts outcomes in aspirin-treated stroke patients
BackgroundAspirin is a cornerstone medication for acute ischemic stroke (AIS), but its efficacy varies significantly among individuals. This study aimed to develop a pharmacogenetic polygenic response score (PgxRS) to predict the incidence of adverse outcomes in aspirin-treated AIS patients.MethodsW...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1519383/full |
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| author | Rui-Nan Ma Dong Zhang Zhi-Zhang Li Ying Ding Xiao-Guang Zhang Jie Xue Dan-Zhuoma Ci Yue-Ying Bai Liang Hu Dai-Zhan Zhou Yun-Hua Yue |
| author_facet | Rui-Nan Ma Dong Zhang Zhi-Zhang Li Ying Ding Xiao-Guang Zhang Jie Xue Dan-Zhuoma Ci Yue-Ying Bai Liang Hu Dai-Zhan Zhou Yun-Hua Yue |
| author_sort | Rui-Nan Ma |
| collection | DOAJ |
| description | BackgroundAspirin is a cornerstone medication for acute ischemic stroke (AIS), but its efficacy varies significantly among individuals. This study aimed to develop a pharmacogenetic polygenic response score (PgxRS) to predict the incidence of adverse outcomes in aspirin-treated AIS patients.MethodsWe conducted a retrospective study involving 828 AIS patients who received aspirin therapy. Fifteen candidate single nucleotide variants (SNPs) in genes related to aspirin’s mechanism of action, transport, metabolism, and platelet function were genotyped. The association between SNPs and the risk of unfavorable prognosis (defined as modified Rankin Scale score >1 at 90 days) was assessed using logistic regression analysis. Multivariable models incorporating SNPs and clinical factors were developed to predict adverse outcomes.ResultsThe rs1045642GG genotype in the ABCB1 gene was significantly associated with a lower risk of unfavorable prognosis, while the rs1371097T allele in the P2Y1 gene was linked to a higher risk. A prediction model incorporating these two SNPs along with clinical variables demonstrated moderate diagnostic accuracy for predicting unfavorable prognosis (AUC = 0.78, 95% CI: 0.74–0.81).ConclusionOur findings suggest that rs1045642 and rs1371097 genotypes contribute to variability in aspirin response among AIS patients. The developed PgxRS, incorporating these SNPs and clinical factors, can potentially aid in risk stratification and guide personalized antiplatelet therapy decisions. However, further validation in larger, diverse cohorts is warranted. |
| format | Article |
| id | doaj-art-3e58d228b8d94cc38967a110f4e43eeb |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-3e58d228b8d94cc38967a110f4e43eeb2025-08-20T02:09:18ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15193831519383Pharmacogenetics polygenic response score predicts outcomes in aspirin-treated stroke patientsRui-Nan Ma0Dong Zhang1Zhi-Zhang Li2Ying Ding3Xiao-Guang Zhang4Jie Xue5Dan-Zhuoma Ci6Yue-Ying Bai7Liang Hu8Dai-Zhan Zhou9Yun-Hua Yue10Department of Neurology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaBiology Department, Boston College, Chestnut Hill, MA, United StatesDepartment of Neurology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, ChinaBackgroundAspirin is a cornerstone medication for acute ischemic stroke (AIS), but its efficacy varies significantly among individuals. This study aimed to develop a pharmacogenetic polygenic response score (PgxRS) to predict the incidence of adverse outcomes in aspirin-treated AIS patients.MethodsWe conducted a retrospective study involving 828 AIS patients who received aspirin therapy. Fifteen candidate single nucleotide variants (SNPs) in genes related to aspirin’s mechanism of action, transport, metabolism, and platelet function were genotyped. The association between SNPs and the risk of unfavorable prognosis (defined as modified Rankin Scale score >1 at 90 days) was assessed using logistic regression analysis. Multivariable models incorporating SNPs and clinical factors were developed to predict adverse outcomes.ResultsThe rs1045642GG genotype in the ABCB1 gene was significantly associated with a lower risk of unfavorable prognosis, while the rs1371097T allele in the P2Y1 gene was linked to a higher risk. A prediction model incorporating these two SNPs along with clinical variables demonstrated moderate diagnostic accuracy for predicting unfavorable prognosis (AUC = 0.78, 95% CI: 0.74–0.81).ConclusionOur findings suggest that rs1045642 and rs1371097 genotypes contribute to variability in aspirin response among AIS patients. The developed PgxRS, incorporating these SNPs and clinical factors, can potentially aid in risk stratification and guide personalized antiplatelet therapy decisions. However, further validation in larger, diverse cohorts is warranted.https://www.frontiersin.org/articles/10.3389/fphar.2025.1519383/fullaspirinacute ischemic strokesingle nucleotide variantpharmacogeneticsprognosispersonalized medicine |
| spellingShingle | Rui-Nan Ma Dong Zhang Zhi-Zhang Li Ying Ding Xiao-Guang Zhang Jie Xue Dan-Zhuoma Ci Yue-Ying Bai Liang Hu Dai-Zhan Zhou Yun-Hua Yue Pharmacogenetics polygenic response score predicts outcomes in aspirin-treated stroke patients Frontiers in Pharmacology aspirin acute ischemic stroke single nucleotide variant pharmacogenetics prognosis personalized medicine |
| title | Pharmacogenetics polygenic response score predicts outcomes in aspirin-treated stroke patients |
| title_full | Pharmacogenetics polygenic response score predicts outcomes in aspirin-treated stroke patients |
| title_fullStr | Pharmacogenetics polygenic response score predicts outcomes in aspirin-treated stroke patients |
| title_full_unstemmed | Pharmacogenetics polygenic response score predicts outcomes in aspirin-treated stroke patients |
| title_short | Pharmacogenetics polygenic response score predicts outcomes in aspirin-treated stroke patients |
| title_sort | pharmacogenetics polygenic response score predicts outcomes in aspirin treated stroke patients |
| topic | aspirin acute ischemic stroke single nucleotide variant pharmacogenetics prognosis personalized medicine |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1519383/full |
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