{"title":"哈萨克斯坦人群中 ABCB1 和 CES1 基因变异对达比加群代谢的影响。","authors":"Ayan Abdrakhmanov, Elena Zholdybayeva, Aizhana Shaimerdinova, Gulmira Kulmambetova, Svetlana Abildinova, Rustam Albayev, Gulnara Tuyakova, Elena Rib, Zhanasyl Suleimen, Zhanar Abdrakhmanova, Makhabbat Bekbossynova","doi":"10.22088/cjim.15.3.499","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Allelic variants of genes encoding enzymes of the esterase system (<i>CES1</i>) and P-glycoprotein (<i>ABCB1</i>) can change the metabolism and pharmacokinetics of dabigatran. Therefore, they act as determining factors in the development of side effects, especially bleeding. We analyzed the genotype-phenotype relationship of <i>ABCB1</i> (rs1045642, rs4148738, rs2032582, and rs1128503) and <i>CES1</i> (rs8192935, rs71647871, and rs2244613) polymorphisms in patients with atrial fibrillation who had been treated with dabigatran.</p><p><strong>Methods: </strong>A total of 150 patients were recruited for this study. TaqMan technology was used for SNP genotyping.</p><p><strong>Results: </strong>Patients with the rs2244613 GG genotype had a lower concentration (55.27 ± 34.22 ng/ml) compared to those with the TT genotype (63.33 ± 52.25 ng/ml) (additive model, P = 0.000). Individuals with the rs8192935 AA genotype had a lower concentration (52.72 ± 30.45 ng/ml) compared to those with the GG genotype (79.78 ± 57 ng/ml) (additive model, P = 0.001). The APTT values among the different genotypes of the <i>ABCB1</i> SNPs, rs4148738 and rs1045642, were significantly different (P = 0.035 and P = 0.024, respectively).</p><p><strong>Conclusion: </strong>Our research demonstrates that the <i>CES1</i> polymorphisms, rs8192935 and rs2244613, are associated with the pharmacodynamics and pharmacokinetics of dabigatran in the Kazakh subpopulation.</p>","PeriodicalId":0,"journal":{"name":"","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246689/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genetic variants of <i>ABCB1</i> and <i>CES1</i> genes on dabigatran metabolism in the Kazakh population.\",\"authors\":\"Ayan Abdrakhmanov, Elena Zholdybayeva, Aizhana Shaimerdinova, Gulmira Kulmambetova, Svetlana Abildinova, Rustam Albayev, Gulnara Tuyakova, Elena Rib, Zhanasyl Suleimen, Zhanar Abdrakhmanova, Makhabbat Bekbossynova\",\"doi\":\"10.22088/cjim.15.3.499\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Allelic variants of genes encoding enzymes of the esterase system (<i>CES1</i>) and P-glycoprotein (<i>ABCB1</i>) can change the metabolism and pharmacokinetics of dabigatran. Therefore, they act as determining factors in the development of side effects, especially bleeding. We analyzed the genotype-phenotype relationship of <i>ABCB1</i> (rs1045642, rs4148738, rs2032582, and rs1128503) and <i>CES1</i> (rs8192935, rs71647871, and rs2244613) polymorphisms in patients with atrial fibrillation who had been treated with dabigatran.</p><p><strong>Methods: </strong>A total of 150 patients were recruited for this study. TaqMan technology was used for SNP genotyping.</p><p><strong>Results: </strong>Patients with the rs2244613 GG genotype had a lower concentration (55.27 ± 34.22 ng/ml) compared to those with the TT genotype (63.33 ± 52.25 ng/ml) (additive model, P = 0.000). Individuals with the rs8192935 AA genotype had a lower concentration (52.72 ± 30.45 ng/ml) compared to those with the GG genotype (79.78 ± 57 ng/ml) (additive model, P = 0.001). The APTT values among the different genotypes of the <i>ABCB1</i> SNPs, rs4148738 and rs1045642, were significantly different (P = 0.035 and P = 0.024, respectively).</p><p><strong>Conclusion: </strong>Our research demonstrates that the <i>CES1</i> polymorphisms, rs8192935 and rs2244613, are associated with the pharmacodynamics and pharmacokinetics of dabigatran in the Kazakh subpopulation.</p>\",\"PeriodicalId\":0,\"journal\":{\"name\":\"\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246689/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.22088/cjim.15.3.499\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.22088/cjim.15.3.499","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Genetic variants of ABCB1 and CES1 genes on dabigatran metabolism in the Kazakh population.
Background: Allelic variants of genes encoding enzymes of the esterase system (CES1) and P-glycoprotein (ABCB1) can change the metabolism and pharmacokinetics of dabigatran. Therefore, they act as determining factors in the development of side effects, especially bleeding. We analyzed the genotype-phenotype relationship of ABCB1 (rs1045642, rs4148738, rs2032582, and rs1128503) and CES1 (rs8192935, rs71647871, and rs2244613) polymorphisms in patients with atrial fibrillation who had been treated with dabigatran.
Methods: A total of 150 patients were recruited for this study. TaqMan technology was used for SNP genotyping.
Results: Patients with the rs2244613 GG genotype had a lower concentration (55.27 ± 34.22 ng/ml) compared to those with the TT genotype (63.33 ± 52.25 ng/ml) (additive model, P = 0.000). Individuals with the rs8192935 AA genotype had a lower concentration (52.72 ± 30.45 ng/ml) compared to those with the GG genotype (79.78 ± 57 ng/ml) (additive model, P = 0.001). The APTT values among the different genotypes of the ABCB1 SNPs, rs4148738 and rs1045642, were significantly different (P = 0.035 and P = 0.024, respectively).
Conclusion: Our research demonstrates that the CES1 polymorphisms, rs8192935 and rs2244613, are associated with the pharmacodynamics and pharmacokinetics of dabigatran in the Kazakh subpopulation.
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