Association of VKORC1 and CYP2C9 single-nucleotide polymorphisms with warfarin dose adjustment in Saudi patients.

IF 13 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2022-04-04 DOI:10.1515/dmdi-2022-0108

Jasmine Holail, Reem Mobarak, Bandar Al-Ghamdi, Ahmad Aljada, Hana Fakhoury

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Abstract

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.

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沙特患者中 VKORC1 和 CYP2C9 单核苷酸多态性与华法林剂量调整的关系。

目的：尽管华法林被广泛使用，但由于其治疗指数窄、个体间反应多变以及出血风险，其治疗仍具有挑战性。以前的报道表明，VKORC1 和 CYP2C9 基因的多态性可能会影响华法林的治疗。在此，我们研究了 VKORC1 -1173C>T、CYP2C9*2 和 CYP2C9*3 基因多态性是否与华法林剂量调整及相关出血事件有关：这项横断面研究的对象是接受华法林治疗超过 1 个月的沙特成年人。方法：这项横断面研究以接受华法林治疗 1 个月以上的沙特成年人为对象，获取了他们的人口统计学和相关临床数据。对 VKORC1 -1173C>T、CYP2C9*2 和 CYP2C9*2 基因型进行了基因分型：结果：与 VKORC1 C/T 和 VKORC1 C/C 相比，同源突变 T 等位基因 VKORC1 T/T 患者所需的华法林每日维持剂量最低。同样，与 CYP2C9*1/*1 组相比，CYP2C9*1/*3 组和 CYP2C9*1/*2 组的华法林每日维持剂量也明显减少。然而，我们发现所研究的多态性与华法林相关出血之间没有明显的相关性：结论：与其他人群相似，沙特患者的 VKORC1 和 CYP2C9 基因多态性与华法林用量有显著相关性。至少存在一个 VKORC1 -1173C>T、CYP2C9*2 和 CYP2C9*3 突变等位基因拷贝与华法林维持剂量的显著减少有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.