中国患者 CYP2C9 和 VKORC1 基因多态性与华法林疗效和安全性的关系

IF 1.7 3区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Pharmacogenetics and genomics Pub Date : 2024-06-01 Epub Date: 2024-03-07 DOI:10.1097/FPC.0000000000000526
Suli Zhang, Mingzhe Zhao, Shilong Zhong, Jiamin Niu, Lijuan Zhou, Bin Zhu, Haili Su, Wei Cao, Qinghe Xing, Hongli Yan, Xia Han, Qihua Fu, Qiang Li, Luan Chen, Fan Yang, Na Zhang, Hao Wu, Lin He, Shengying Qin
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引用次数: 0

摘要

目的:遗传变异是导致华法林剂量需求个体间差异的主要因素。导致华法林出血并发症的具体遗传因素尚不清楚,尤其是在中国患者中。本研究共招募了 896 名中国患者,以探讨 CYP2C9 和 VKORC1 基因变异对华法林疗效和安全性的影响:单变量分析揭示了CYP2C9中的两个特定单核苷酸多态性rs1057910和VKORC1中的rs9923231与华法林稳定剂量之间的显著相关性:特定基因变异与华法林稳定剂量和出血风险之间的关联可能是基因检测在优化华法林治疗以提高患者疗效和安全性方面的潜在意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Association between CYP2C9 and VKORC1 genetic polymorphisms and efficacy and safety of warfarin in Chinese patients.

Objectives: Genetic variation has been a major contributor to interindividual variability of warfarin dosage requirement. The specific genetic factors contributing to warfarin bleeding complications are largely unknown, particularly in Chinese patients. In this study, 896 Chinese patients were enrolled to explore the effect of CYP2C9 and VKORC1 genetic variations on both the efficacy and safety of warfarin therapy.

Methods and results: Univariate analyses unveiled significant associations between two specific single nucleotide polymorphisms rs1057910 in CYP2C9 and rs9923231 in VKORC1 and stable warfarin dosage ( P  < 0.001). Further, employing multivariate logistic regression analysis adjusted for age, sex and height, the investigation revealed that patients harboring at least one variant allele in CYP2C9 exhibited a heightened risk of bleeding events compared to those with the wild-type genotype (odds ratio = 2.16, P  = 0.04). Moreover, a meta-analysis conducted to consolidate findings confirmed the associations of both CYP2C9 (rs1057910) and VKORC1 (rs9923231) with stable warfarin dosage. Notably, CYP2C9 variant genotypes were significantly linked to an increased risk of hemorrhagic complications ( P  < 0.00001), VKORC1 did not demonstrate a similar association.

Conclusion: The associations found between specific genetic variants and both stable warfarin dosage and bleeding risk might be the potential significance of gene detection in optimizing warfarin therapy for improving patient efficacy and safety.

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来源期刊
Pharmacogenetics and genomics
Pharmacogenetics and genomics 医学-生物工程与应用微生物
CiteScore
3.20
自引率
3.80%
发文量
47
审稿时长
3 months
期刊介绍: ​​​​Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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