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VKORC1 variants as significant predictors of warfarin dose in Emiratis

机译：VKORC1变体是阿联酋华法林剂量的重要预测指标

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Purpose: Variability in response to warfarin is one of the main obstacles challenging its use in clinical practice. Vitamin K epoxide reductase complex (VKORC) is the target enzyme of warfarin, and variations in the form of single nucleotide polymorphisms (SNPs) in VKORC1 , coding for this enzyme, are known to cause resistance to warfarin treatment. This study aimed to explore VKORC1 variants in Emirati patients receiving warfarin treatment and to correlate their genotypes at the studied SNPs to their maintenance warfarin dose. Patients and methods: Sanger sequencing of the majority of the VKORC1 gene was applied to samples from 90 patients and 117 normal individuals recruited from Tawam Hospital, Al-Ain, UAE. Genotypes at the following variants were determined (rs9923231, rs188009042, rs61742245, rs17708472, rs9934438, rs8050894, rs2359612, rs7294). Statistical analysis was applied, including ANOVA, cross-tabulation, and multiple linear regression analysis, to determine the ability of nongenetic factors (age and gender) and genetic factors ( VKORC1 genotypes) to explain variability in warfarin dose in patients. Results: Different frequencies of minor alleles were detected in the selected SNPs. Significant variation among genotypes at six VKORC1 variants were identified (rs9923231, rs9934438, rs8050894, rs2359612, rs7294). The main predictors for warfarin dose were rs9923231, age, and rs61742245 with 50.7% of the average warfarin dose in our sample could be explained by a regression model built on these three factors. Conclusion: This is the first report of the explanatory power of VKORC1 genotypes and nongenetic factors (age and gender) on warfarin dose among Emiratis. Also, this study highlighted the positive effect of considering rare pharmacogenomic variants on explaining warfarin dose variability.
机译：目的：对华法令的反应变异性是挑战其在临床实践中使用的主要障碍之一。维生素K环氧还原酶复合物（VKORC）是华法林的靶标酶，已知编码该酶的VKORC1中单核苷酸多态性（SNP）形式的变化会引起对华法林治疗的耐药性。这项研究旨在探讨接受华法林治疗的阿联酋患者中的VKORC1变异体，并将他们在研究的S​​NPs上的基因型与其华法林维持剂量相关联。患者和方法：将大多数VKORC1基因的Sanger测序应用于从阿联酋Al-Ain的Tawam医院招募的90名患者和117名正常个体的样本中。确定了以下变体的基因型（rs9923231，rs188009042，rs61742245，rs17708472，rs9934438，rs8050894，rs2359612，rs7294）。应用统计分析，包括方差分析，交叉表分析和多元线性回归分析，以确定非遗传因素（年龄和性别）和遗传因素（VKORC1基因型）解释患者华法林剂量变异性的能力。结果：在选定的SNP中检测到不同频率的次要等位基因。确定了六个VKORC1变体的基因型之间的显着差异（rs9923231，rs9934438，rs8050894，rs2359612，rs7294）。华法林剂量的主要预测因子是rs9923231，年龄和rs61742245，我们样本中华法林平均剂量的50.7％可以通过基于这三个因素的回归模型来解释。结论：这是首次报道VKORC1基因型和非遗传因素（年龄和性别）对阿联酋华法林剂量的解释能力。此外，这项研究还强调了考虑罕见的药物基因组变异对解释华法林剂量变异性的积极作用。

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