血浆蛋白C基因多态性与华法林剂量相关性的研究  

Association of PROC Genetic Polymorphism with Warfarin Dose

作　　者：张海燕[1] 方焕荣[1] 杨协清[1] 罗万慰 许联红[2] 马守梅 

机构地区：[1]江苏大学附属武进医院药剂科,江苏常州213002 [2]江苏大学附属武进医院中心实验室,江苏常州213002 [3]江苏大学附属武进医院心胸外科,江苏常州213002

出　　处：《中国药学杂志》2012年第21期1741-1745,共5页Chinese Pharmaceutical Journal

摘　　要：目的探讨中国苏南地区心脏机械瓣膜置换术后汉族人群血浆蛋白C(PROC)基因rs5936多态性与华法林剂量的相关性,为利用基因多态性指导临床合理用药提供理论依据。方法采用限制性片段长度多态性技术以及碱基淬灭探针技术分别检测188名心脏机械瓣膜置换术后患者VKORC1-1639G>A,CYP2C9 1075A>C和PROC rs5936的基因型,分析与华法林剂量的相关性。结果 PROC rs5936等位基因频率T 54.78%,G 45.22%,华法林的平均稳定剂量GG型为(2.55±0.81)mg.d-1,TG型(2.65±0.96)mg.d-1,TT型为(2.64±0.74)mg.d-1,各组间华法林剂量差异无统计学意义(P>0.05);VKORC1-1639G>A和CYP2C9 1075A>C基因多态性对华法林剂量的影响均有统计学意义(P<0.001),并分别解释30.2%和7.0%的华法林剂量差异。结论在中国苏南地区心脏机械瓣膜置换术后汉族人群中,VKORC1-1639G>A和CYP2C91075A>C基因多态性与华法林剂量有显著相关性,而PROC rs5936基因多态性与华法林剂量无相关性。ABSTRACT ： OBJECTIVE To investigate the association of PROC rs5936 polymorphism with warfarin maintenance dose in the Han population in the south of Jiangsu province. METHODS The single nucleotide polymorphism was detected by base-quenched probe technique and PCR-RFLP technique. VKORC1 -1639G 〉 A, CYP2C9 1075A 〉 C and PROC rs5936 polymorphisms were analyzed in 188 patients after mechanical heart valve replacement. RESULTS Among the 188 patients, the genotypic frequency of PROC rs5936 was T 54. 78% and G 45.22%. The required warfarin doses for patients with different PROC rs5936 GG genotypes were （ 2. 55 ± 0. 81） mg · d-1 for GG, （2.65±0.96） mg · d-1 for TG,and（2.64 ±0.74） mg · d-1 for TT, respectively. PROCrs5936 genotype did not show association with warfarin dose （P 〉0. 05）. The genotypes of VKORC1 -1639G 〉 A and CYP2C9 1075A 〉 C had significant association with warfarin dose （ P 〈 0.001 ）, and accounted for respectively 30.2% and 7% variance of warfarin dose. CON- CLUSION VKORC1 -1639G 〉 A and CYP2C9 1075A 〉 C genotypes have significant association with the dose of warfarin , yet, no impact was observed for PROC rs5936 in the Han population of the south of Jiangsu province. KEY WORDS ： PROC ; warfarin ; polymorphism

关 键 词：血浆蛋白C 华法林 基因多态性 

分 类 号：I1968[文学—世界文学]