Abdur Razaq, Waheed Iqbal, Syed Tahir Shah, Muhammad Abdur Rauf, Nasser M Aldekhail, Filip Van Nieuwerburgh, Sami Siraj
{"title":"ABCB1基因多态性对pci术后患者氯吡格雷血药浓度及心血管事件的影响","authors":"Abdur Razaq, Waheed Iqbal, Syed Tahir Shah, Muhammad Abdur Rauf, Nasser M Aldekhail, Filip Van Nieuwerburgh, Sami Siraj","doi":"10.1080/14622416.2025.2534325","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>This study investigated the impact of ABCB1 gene polymorphisms on clopidogrel absorption and therapeutic response by analyzing plasma levels of the clopidogrel carboxylic acid metabolite (CAM), and cardiovascular events (CVEs) in patients undergoing percutaneous coronary intervention (PCI).</p><p><strong>Methods: </strong>A prospective cohort study of 264 post-PCI patients was conducted in Peshawar, Pakistan. CVEs over 12 months were recorded. Plasma concentrations of CAM were measured by high-performance liquid chromatography (HPLC), while the ABCB1 gene (rs1045642) was genotyped by Sanger sequencing to determine associations between genetic variants, CAM levels, and clinical outcomes.</p><p><strong>Results: </strong>The study documented 54 CVEs, including 13 deaths, 6 stent thromboses, 10 recurrent myocardial infarctions, 23 ischemic events requiring hospitalization, and 2 strokes. The analysis showed that 31.1% of patients had subtherapeutic CAM levels ( <2000 ng/ml), while 68.9% had therapeutic levels. Genetic analysis identified 65% as poor absorbers (CT/TT genotypes) and 35% as good absorbers (CC genotype), while CAM levels were significantly associated with the CT/TT genotype (<i>p</i> < 0.005).</p><p><strong>Conclusion: </strong>This study linking ABCB1 variation to CAM concentration and therapeutic outcomes. There was a significant association between ABCB1 variants and CAM concentrations. However, no association was found between ABCB1 polymorphisms and CVEs.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"1-8"},"PeriodicalIF":1.9000,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of <i>ABCB1</i> gene polymorphism on clopidogrel plasma concentration and cardiovascular events in post-PCI patients.\",\"authors\":\"Abdur Razaq, Waheed Iqbal, Syed Tahir Shah, Muhammad Abdur Rauf, Nasser M Aldekhail, Filip Van Nieuwerburgh, Sami Siraj\",\"doi\":\"10.1080/14622416.2025.2534325\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>This study investigated the impact of ABCB1 gene polymorphisms on clopidogrel absorption and therapeutic response by analyzing plasma levels of the clopidogrel carboxylic acid metabolite (CAM), and cardiovascular events (CVEs) in patients undergoing percutaneous coronary intervention (PCI).</p><p><strong>Methods: </strong>A prospective cohort study of 264 post-PCI patients was conducted in Peshawar, Pakistan. CVEs over 12 months were recorded. Plasma concentrations of CAM were measured by high-performance liquid chromatography (HPLC), while the ABCB1 gene (rs1045642) was genotyped by Sanger sequencing to determine associations between genetic variants, CAM levels, and clinical outcomes.</p><p><strong>Results: </strong>The study documented 54 CVEs, including 13 deaths, 6 stent thromboses, 10 recurrent myocardial infarctions, 23 ischemic events requiring hospitalization, and 2 strokes. The analysis showed that 31.1% of patients had subtherapeutic CAM levels ( <2000 ng/ml), while 68.9% had therapeutic levels. Genetic analysis identified 65% as poor absorbers (CT/TT genotypes) and 35% as good absorbers (CC genotype), while CAM levels were significantly associated with the CT/TT genotype (<i>p</i> < 0.005).</p><p><strong>Conclusion: </strong>This study linking ABCB1 variation to CAM concentration and therapeutic outcomes. There was a significant association between ABCB1 variants and CAM concentrations. However, no association was found between ABCB1 polymorphisms and CVEs.</p>\",\"PeriodicalId\":20018,\"journal\":{\"name\":\"Pharmacogenomics\",\"volume\":\" \",\"pages\":\"1-8\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-07-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacogenomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/14622416.2025.2534325\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14622416.2025.2534325","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Impact of ABCB1 gene polymorphism on clopidogrel plasma concentration and cardiovascular events in post-PCI patients.
Aim: This study investigated the impact of ABCB1 gene polymorphisms on clopidogrel absorption and therapeutic response by analyzing plasma levels of the clopidogrel carboxylic acid metabolite (CAM), and cardiovascular events (CVEs) in patients undergoing percutaneous coronary intervention (PCI).
Methods: A prospective cohort study of 264 post-PCI patients was conducted in Peshawar, Pakistan. CVEs over 12 months were recorded. Plasma concentrations of CAM were measured by high-performance liquid chromatography (HPLC), while the ABCB1 gene (rs1045642) was genotyped by Sanger sequencing to determine associations between genetic variants, CAM levels, and clinical outcomes.
Results: The study documented 54 CVEs, including 13 deaths, 6 stent thromboses, 10 recurrent myocardial infarctions, 23 ischemic events requiring hospitalization, and 2 strokes. The analysis showed that 31.1% of patients had subtherapeutic CAM levels ( <2000 ng/ml), while 68.9% had therapeutic levels. Genetic analysis identified 65% as poor absorbers (CT/TT genotypes) and 35% as good absorbers (CC genotype), while CAM levels were significantly associated with the CT/TT genotype (p < 0.005).
Conclusion: This study linking ABCB1 variation to CAM concentration and therapeutic outcomes. There was a significant association between ABCB1 variants and CAM concentrations. However, no association was found between ABCB1 polymorphisms and CVEs.
期刊介绍:
Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field.
Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.