摘要
目的探讨CYP2C9、CYP4F2和VKORC1基因多态性对中国汉族人群中华法林稳定剂量的影响,评价华法林用药遗传背景,为临床个体化用药奠定基础。方法采用PCR-HRM法对181例接受华法林治疗并达到稳定剂量的中国汉族患者检测CYP2C9*2、CYP2C9*3、CYP4F2 V433M和VKORC1 1173C/T四个SNP位点的多态性。基因分型数据结合临床资料(性别、年龄和华法林剂量等)进行统计学分析并建立数学模型。结果 20岁以下年龄组与70岁以上年龄组间华法林剂量有统计学差异(P=0.041),且随着年龄的增长,华法林剂量有降低趋势;CYP2C9*3基因型CA(杂合突变型)华法林日平均剂量(1.93mg)比AA(野生型)日平均剂量(2.96mg)低1mg(P=0.001);VKORC1 1173C/T基因型CT(杂合突变型)华法林日平均剂量(3.34mg)比TT(野生型)日平均剂量(2.77mg)高0.57mg(P=0.002);CYP4F2 V433M基因型TT(纯合突变型)华法林日平均剂量(3.52mg)比CT(杂合突变型)高0.68mg(P=0.021),比CC(野生型)高0.72mg(P=0.026)。结论华法林剂量受CYP2C9、CYP4F2、VKORC1基因多态性和年龄的影响,临床用药前进行CYP2C9、CYP4F2、VKORC1基因多态性检测有助于华法林抗凝治疗用药剂量的评估。
Objective To explore the influence of CYP2C9,CYP4F2 and VKORC1 genetic polymorphism on stable Warfarin dosage in Chinese Han population for clinical personalized medication and to evaluate the relationship between Warfarin dosage and genetic factor. Methods PCR-HRM（high resolution melting） technique was used to detect the single nucleotide polymorphisms（SNPs） of CYP2C9＊2, CYP2C9＊3, CYP4F2 V433M and VKORC1 1173C/T genes in 181 patients taking stable Warfarin dosage treatment of Chinese Han population in Lanzhou region. The genotype data was gathered with clinical material, including gender, age and warfarin dosage, to carry out statistical analysis and set up computation model. Results Significant difference was found between the group of age less than 20 years old and the group of age more than 70 years old（P=0.041）, and there was a decreased trend of Warfarin dosage with age increasing. The average day dosage of Warfarin in patients with CYP2C9＊3 CA was 1 mg lower than that with CYP2C9＊3 AA（P=0.001）; VKORC1 1173C/T was 0.57 mg higher than VKORC1 1173 TT（P=0.002）; CYP4F2 V433M TT was 0.72mg higher than CYP4F2 V433M CC（P=-0.026）, 0.68 mg higher than CYP4F2 V433M CT（P=0.021）. Conclusion The Warfarin treatment dosage was affected by the age and genetic polymorphisms of CYP2C9, CYP4F2 and VKORC1 of patients, so detecting the SNPs before clinical medication is helpful to evaluate Warfarin medication dosage correctly.
出处
《分子诊断与治疗杂志》
2012年第2期89-94,共6页
Journal of Molecular Diagnostics and Therapy
基金
甘肃省科技支撑项目(090NKCA094)
作者简介
尤崇革，E-mail：youchg@lzu．edu．cn
