云南汉族人群VKORC1 1173C/T基因多态性与华法林抗凝治疗维持剂量的相关性研究

Relationship between Genetic Polymorphism of VKORC1 1173C/T and Warfarin Dose Requirments in Yunnan Han Population

目的研究云南汉族人群维生素K环氧化物还原酶复合体亚单位1基因VKORC1 1173C/T多态性分布及与其他群体间的差异,并探讨其与华法林抗凝维持剂量的分子遗传关系.方法采集300名心脏机械瓣膜置换术后服用华法林抗凝已达稳定剂量、凝血酶原时间国际标准化比值在目的范围(1.5～3.0)病人的外周血,采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)分析技术,检测VKORC1 1173C/T基因位点的基因型和等位基因频率,探讨华法林抗凝维持剂量与该基因多态性的关系.结果在所有的样本中,VKORC1 1173C/T基因共检出C(10%)和T(90%)2种等位基因,纯合子TT(80%)和杂合子CT(20%)两种基因型,云南汉族人群中VKORC1 1173C/T基因多态性分布在性别和年龄上无差异;CT基因型病人所需华法林维持剂量最高(3.62±1.35)mg/d,其次是TT基因型病人(3.12±1.17)mg/d.结论与其他群体相比,云南汉族人群VKORC11173C/T基因位点具有自己的遗传多态性,其基因型在华法林抗凝治疗中具有非常重要的意义.

Objective To investigate the polymorphism distribution and characteristics of VKORC1 1173C/T, as well as the relationship between the polymorphism and warfarin dose requirments in Han population in Yunnan. Methods Blood samples were collected from 300 patients with stable warfarin dose requirements, PCR-RFLP techniques were used to detect genes and genotypes of VKORC1 1173C/T, and international normalized ratio （INR） of the prothrombin time within the target range （1.5-3.0） , polymorphisms for VKORC1 1173CfI＇ were also analyzed. Results We obtained two alleles of C and T, with the frequencies of 10% and 90% , respectively. The genotypes showed that 80% patients were homozygous TI; and 20% were heterozygous CT. No differences were found between age and gender. Patients with CT genotypes required higher warfarin dose （3.62 ±1.35 mg/day） than those with TT （3.12 ± 1.17 mg/day; CT：TT p =0.007）. Conclusion VKORC1 1173C/T gene distribution in Yunnan Han is different from those in other populations, and some suggestions are given for individual use of warfarin in Yunan Han population.