内蒙古地区蒙古族VKORC1-1639 G/A和CYP2C9基因多态性与华法林应用剂量关系的研究

Study of VKORC1 and CYP2C9 Plymorphism on Dosage of Warfarin in Atrial Fibrillation Patients in Inner Mongolian Area

目的探讨内蒙古地区蒙古族维生素K环氧化物还原酶复合物1(VKORC1)-1639 G/A及CYP2C9基因多态性分布特点及对华法林应用剂量的影响。方法选择300例蒙古族心房颤动病人(蒙古族组)和300例汉族心房颤动病人(对照组),PCRRFLP法检测两组VKORC1-1639 G/A及CYP2C9基因型分布,同时记录华法林剂量及国际标准化比值(INR)。计算不同VKORC1及CYP2C9基因型间平均校正华法林剂量。结果蒙古族组VKORC1-1639 AA、AG、GG基因型分布频率分别为78%、18%、4%;等位基因A和G频率分别为87%、13%。对照组VKORC1-1639 AA、AG、GG基因型分布频率分别为79%、19%、2%;等位基因A和G频率分别为86%、14%。蒙古族CYP2C9*1/*1型276例,CYP2C9*1/*3型24例。汉族CYP2C9*1/*1型279例,CYP2C9*1/*3型21例。不同VKORC1、CYP2C9基因型房颤病人华法林用量不同,VKORC1 AA型并CYP2C9*1/*1型和VKORC1 AG型并CYP2C9*1/*1型病人华法林日用量均高于VKORC1 AA型并CYP2C9*1/*3型病人;VKORC1 AG型并CYP2C9*1/*1型病人华法林用量高于VKORC1 AA型并CYP2C9*1/*1型病人,3组比较,差异有统计学意义(P<0.05)。结论蒙古族与汉族基因型VKORC1-1639 G/A及CYP2C9一致,多态性均为VKORC1-1639 AA及CYP2C9*1/*1型均占多数,不同基因型影响个体间华法林的维持应用剂量。

Objective To investigate the relationship between vitamin K oxide reductase complex subunit 1（ VKORC1）-1639 G / A and cytochrome P450（ CYP） 2C9 genetic polymorphicmand warfarin dosage in inner Mongolian populations. Methods The patients with atrialfibrillationwere divided into two groups： Mongolian group（n = 300,Mongolian populations） and compared group（n = 300,Han populations）.PCR-RFLP were used to analysis the VKORC1-1639 G / A and CYP2C9 genetic polymorphism,and the international normalized ratio（ INR）in every patients were recorded. The mean warfarin dosage was compared according to different VKORC1 genotypes. Resluts The frequencies of the VKORC1-1639 AA,AG,GG genotypes in the Mongolian patient group were 78%,18% and 4%,and 76. 5%,19%,4. 5% in compared group. The alleles frequencies of VKORC1-1639 A and G were 87% and 13% in the Mongolian patient group,and 86% and 14% in compared group（P = 0. 26）. The maintenance doses of warfarin was（ 2. 98 ± 1. 6） mg / d in AA genotype group,（ 3. 67 ± 1. 8） mg / d in AG genotype group and（ 4. 36 ± 2. 0） mg / d in GG genotype,respectively. There were 276 patients were CYP2C9 ＊ 1 / ＊ 1,24 patients were CYP2C9＊ 1 / ＊ 3 in the Mongolian patient,279 patients were CYP2C9＊ 1 / ＊ 1,21 patients were CYP2C9＊ 1 / ＊ 3 in the compared group.There was a significantly different among different VKORC1 and CYP2C9 genotypes patients（P〈0. 05）. The dosage in CYP2C9 ＊ 1 / ＊ 1with VKORC1 AG patients were higher than the other groups,and the dosage in CYP2C9＊ 1 / ＊ 1 with VKORC1 AA were higher than that in CYP2C9 ＊ 1 / ＊ 3 with VKORC1 AA groups. Conclusion There was no significant difference ingenotype distribution of VKORC1-1639 G / A and CYP2C9 between the Mongolian patients and the Chinese Han population patient,but the VKORC1-1639 AA,AG,GG and CYP2C9＊ 1 /＊ 1,CYP2C9＊ 1 / ＊ 3 genotypes influent the warfarin dosage.