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与CYP2C9基因多态性相关的华法林维持剂量

Warfarin maintenance dose associated with genetic polymorphisms of CYP2C9.

作者信息

Khaleqsefat E, Khalaj-Kondori M, Jabbarpour Bonyadi, Battaloğlu E

机构信息

Department of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.

Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul, Turkey.

出版信息

Hippokratia. 2017 Apr-Jun;21(2):93-96.

Abstract

BACKGROUND

Cytochrome P450 2C9 () gene polymorphisms alters the required warfarin dose in patients, due to pharmacogenetic events. This study aimed to identify the frequency of the allele polymorphic variants *2 and *3, and the association of these allelic variants with warfarin dosage in the population of the west Azerbaijan province in Iran.

METHODS

One hundred and seventy patients receiving warfarin were examined to evaluate the genotype frequency of common polymorphisms. Genotype analysis for *2 and *3 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. To assess if the dosage is different between genotypes we used one-way analysis of variance (ANOVA).

RESULTS

Frequency of the two variants in studied subjects was 12 % for *2 and 25.8 % for *3. Comparison of the warfarin daily maintenance dose between genotype groups showed that the daily mean dose of warfarin in patients who have homozygous wild-type genotype for (1/1) was 5.26 ± 2.32 mg, which was significantly higher compared to 1/2, 1/3 (3.57 ± 2.25 mg, p <0.001) and 2/2, 2/3 and 3/3 patients (3.76 ± 2.4 mg, p =0.024). Further analysis revealed that the allelic frequency of polymorphisms in the study population was similar to that of the Turkish population.

CONCLUSIONS

Due to the relatively high frequency of polymorphisms in the study population, the clinicians should become aware of these results to reduce the risk of hemorrhage when prescribing warfarin. HIPPOKRATIA 2017, 21(2): 93-96.

摘要

背景

由于药物遗传学事件,细胞色素P450 2C9(CYP2C9)基因多态性会改变患者所需的华法林剂量。本研究旨在确定伊朗西阿塞拜疆省人群中CYP2C9等位基因多态性变体2和3的频率,以及这些等位基因变体与华法林剂量的关联。

方法

对170名接受华法林治疗的患者进行检查,以评估常见CYP2C9多态性的基因型频率。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析对2和3多态性进行基因型分析。为了评估不同基因型之间的剂量是否存在差异,我们使用了单因素方差分析(ANOVA)。

结果

研究对象中两种变体的频率分别为:*2为12%,*3为25.8%。基因型组之间华法林每日维持剂量的比较表明,CYP2C9纯合野生型基因型(1/1)患者的华法林每日平均剂量为5.26±2.32mg,与1/2、1/3患者(3.57±2.25mg,p<0.001)以及2/2、2/3和3/3患者(3.76±2.4mg,p = 0.024)相比显著更高。进一步分析显示,研究人群中CYP2C9多态性的等位基因频率与土耳其人群相似。

结论

由于研究人群中CYP2C9多态性频率相对较高,临床医生在开具华法林处方时应了解这些结果,以降低出血风险。《希波克拉底》2017年,21(2): 93 - 96。

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