Jasmine Holail, Reem Mobarak, Bandar Al-Ghamdi, Ahmad Aljada, Hana Fakhoury
{"title":"沙特患者VKORC1和CYP2C9单核苷酸多态性与华法林剂量调整的关系","authors":"Jasmine Holail, Reem Mobarak, Bandar Al-Ghamdi, Ahmad Aljada, Hana Fakhoury","doi":"10.1515/dmpt-2022-0108","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Despite its wide usage, warfarin therapy remains challenging due to its narrow therapeutic index, inter-individual response variability, and risk of bleeding. Previous reports have suggested that polymorphisms in <i>VKORC1</i> and <i>CYP2C9</i> genes could influence warfarin therapy. Herein, we investigated whether <i>VKORC1</i> -1173C>T, <i>CYP2C9*2</i>, and <i>CYP2C9*3</i> gene polymorphisms are associated with warfarin dose adjustment and related bleeding events.</p><p><strong>Methods: </strong>This cross-sectional study was conducted on Saudi adults receiving warfarin for more than 1 month. Their demographics and relevant clinical data were obtained. Genotyping for <i>VKORC1</i> -1173C>T, <i>CYP2C9*2</i>, and <i>CYP2C9*2</i> genotypes was performed.</p><p><strong>Results: </strong>Patients who are homozygous for the mutant T allele <i>VKORC1</i> T/T required the lowest warfarin daily maintenance dose, compared to <i>VKORC1</i> C/T and <i>VKORC1</i> C/C. Similarly, there was a significant reduction in warfarin daily maintenance dose among <i>CYP2C9*1/*3</i> and <i>CYP2C9*1/*2</i> groups compared to <i>CYP2C9*1/*1</i>. However, we found no significant correlation between the studied polymorphisms and warfarin-associated bleeding.</p><p><strong>Conclusions: </strong>Similar to other populations, the <i>VKORC1</i> and <i>CYP2C9</i> gene polymorphisms are significantly associated with warfarin dosage in Saudi patients. The presence of at least one copy of the mutant alleles for <i>VKORC1</i> -1173C>T, <i>CYP2C9*2</i>, and <i>CYP2C9*3</i> is associated with a significant reduction in warfarin maintenance dose.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"37 4","pages":"353-359"},"PeriodicalIF":0.0000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Association of <i>VKORC1</i> and <i>CYP2C9</i> single-nucleotide polymorphisms with warfarin dose adjustment in Saudi patients.\",\"authors\":\"Jasmine Holail, Reem Mobarak, Bandar Al-Ghamdi, Ahmad Aljada, Hana Fakhoury\",\"doi\":\"10.1515/dmpt-2022-0108\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Despite its wide usage, warfarin therapy remains challenging due to its narrow therapeutic index, inter-individual response variability, and risk of bleeding. Previous reports have suggested that polymorphisms in <i>VKORC1</i> and <i>CYP2C9</i> genes could influence warfarin therapy. Herein, we investigated whether <i>VKORC1</i> -1173C>T, <i>CYP2C9*2</i>, and <i>CYP2C9*3</i> gene polymorphisms are associated with warfarin dose adjustment and related bleeding events.</p><p><strong>Methods: </strong>This cross-sectional study was conducted on Saudi adults receiving warfarin for more than 1 month. Their demographics and relevant clinical data were obtained. Genotyping for <i>VKORC1</i> -1173C>T, <i>CYP2C9*2</i>, and <i>CYP2C9*2</i> genotypes was performed.</p><p><strong>Results: </strong>Patients who are homozygous for the mutant T allele <i>VKORC1</i> T/T required the lowest warfarin daily maintenance dose, compared to <i>VKORC1</i> C/T and <i>VKORC1</i> C/C. Similarly, there was a significant reduction in warfarin daily maintenance dose among <i>CYP2C9*1/*3</i> and <i>CYP2C9*1/*2</i> groups compared to <i>CYP2C9*1/*1</i>. However, we found no significant correlation between the studied polymorphisms and warfarin-associated bleeding.</p><p><strong>Conclusions: </strong>Similar to other populations, the <i>VKORC1</i> and <i>CYP2C9</i> gene polymorphisms are significantly associated with warfarin dosage in Saudi patients. The presence of at least one copy of the mutant alleles for <i>VKORC1</i> -1173C>T, <i>CYP2C9*2</i>, and <i>CYP2C9*3</i> is associated with a significant reduction in warfarin maintenance dose.</p>\",\"PeriodicalId\":11332,\"journal\":{\"name\":\"Drug metabolism and personalized therapy\",\"volume\":\"37 4\",\"pages\":\"353-359\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug metabolism and personalized therapy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1515/dmpt-2022-0108\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug metabolism and personalized therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/dmpt-2022-0108","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
Association of VKORC1 and CYP2C9 single-nucleotide polymorphisms with warfarin dose adjustment in Saudi patients.
Objectives: Despite its wide usage, warfarin therapy remains challenging due to its narrow therapeutic index, inter-individual response variability, and risk of bleeding. Previous reports have suggested that polymorphisms in VKORC1 and CYP2C9 genes could influence warfarin therapy. Herein, we investigated whether VKORC1 -1173C>T, CYP2C9*2, and CYP2C9*3 gene polymorphisms are associated with warfarin dose adjustment and related bleeding events.
Methods: This cross-sectional study was conducted on Saudi adults receiving warfarin for more than 1 month. Their demographics and relevant clinical data were obtained. Genotyping for VKORC1 -1173C>T, CYP2C9*2, and CYP2C9*2 genotypes was performed.
Results: Patients who are homozygous for the mutant T allele VKORC1 T/T required the lowest warfarin daily maintenance dose, compared to VKORC1 C/T and VKORC1 C/C. Similarly, there was a significant reduction in warfarin daily maintenance dose among CYP2C9*1/*3 and CYP2C9*1/*2 groups compared to CYP2C9*1/*1. However, we found no significant correlation between the studied polymorphisms and warfarin-associated bleeding.
Conclusions: Similar to other populations, the VKORC1 and CYP2C9 gene polymorphisms are significantly associated with warfarin dosage in Saudi patients. The presence of at least one copy of the mutant alleles for VKORC1 -1173C>T, CYP2C9*2, and CYP2C9*3 is associated with a significant reduction in warfarin maintenance dose.
期刊介绍：
Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.
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