Yasmeen Faiza, Ghafoor Muhammad Bilal, Khalid Abdul Wadood, Latif Waqas, Mohsin Shahida, Khaliq Shagufta
Department of Haematology, University of Health Sciences (UHS), Lahore, Pakistan,
J Thromb Thrombolysis. 2015 Aug;40(2):218-24. doi: 10.1007/s11239-015-1215-5.
Warfarin is a widely used anticoagulant characterized by having a narrow therapeutic index and exhibiting a wide range of inter-individual and inter-ethnic variation. Single nucleotide polymorphisms in hepatic VKORC1 and CYP2C9 genes causes decreased and increased metabolism of warfarin respectively. The objective of this study was to evaluate the allele frequency of CYP2C9 polymorphic variants *2 and *3 and the association of these allelic variants with PT/INR and daily/weekly dose of warfarin. Seventy-four patients with heart valve replacement were selected. Patients taking low warfarin dose (4.90-17.50 mg weekly) for at least last 3 months and had a stable INR in the range of 2-3 were included in this study. CYP2C9 polymorphism was analyzed by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) technique. Among 74 patients, 9 (12.1 %) showed to have *2 allele, whereas 11 (14.1 %) had *3 allele. Genotype frequencies of wild and variant alleles were, 54.1, 17.6, 21.6 and 6.8 % for *1/*1, *1/*2, *1/*3 and *2/*3 respectively. None of the patient was homozygous for *2 and *3. Statistical analysis showed that low warfarin dose (weekly) is significantly associated with *1/*2 and *1/*3 genotypes (p value ≥ 0.001), whereas PT/INR showed no significant association with the any genotypes of CYP2C9. Our study suggest that polymorphic variants of CYP2C9 (*2 and *3) might influence warfarin dose requirements and associated with the low dose of warfarin in patients.
华法林是一种广泛使用的抗凝剂，其特点是治疗指数狭窄，个体间和种族间存在广泛差异。肝脏中维生素K环氧化物还原酶复合体1（VKORC1）和细胞色素P450 2C9（CYP2C9）基因的单核苷酸多态性分别导致华法林代谢减少和增加。本研究的目的是评估CYP2C9基因多态性变体2和3的等位基因频率，以及这些等位基因变体与凝血酶原时间（PT）/国际标准化比值（INR）和华法林每日/每周剂量的相关性。选取了74例心脏瓣膜置换患者。本研究纳入了至少在过去3个月内服用低剂量华法林（每周4.90 - 17.50毫克）且INR稳定在2 - 3范围内的患者。采用聚合酶链反应随后进行限制性片段长度多态性（PCR-RFLP）技术分析CYP2C9基因多态性。在74例患者中，9例（12.1%）显示有2等位基因，而11例（14.1%）有3等位基因。野生型和变异型等位基因的基因型频率分别为：*1/*1为54.1%，*1/*2为17.6%，*1/3为21.6%，2/3为6.8%。没有患者是2和3的纯合子。统计分析表明，低剂量华法林（每周）与1/2和1/*3基因型显著相关（p值≥0.001），而PT/INR与CYP2C9的任何基因型均无显著相关性。我们的研究表明，CYP2C9基因多态性变体（2和3）可能影响华法林的剂量需求，并与患者低剂量华法林使用有关。
