NR1I2基因多态性对华法林维持剂量个体差异的影响

目的探讨NR1I2相关单核苷酸多态性对华法林维持剂量个体差异的影响。方法共179名机械瓣膜置换术后患者纳入研究。NR1I2-25385C>T,NR1I2 7635G>A基因型检测采用直接测序法,VKORC1-1639 G>A,CYP2C9*3基因型检测采用PCR-RFLP法;判断患者是否入选的INR值、及华法林维持剂量均通过查阅患者定期复诊的电子病历获得;统计分析NR1I2-25385C>T,NR1I2 7635G>A的基因分布频率,及其与华法林维持剂量的相关性。结果 179名机械瓣膜置换术患者中,NR1I2-25385C>T的基因型频率分布为CC型62.6%、CT型31.3%和TT型6.1%;NR1I2 7635G>A的基因型频率分布为GG型30.7%、GA型49.2%和AA型20.1%。NR1I2-25385 C>T各基因型组的剂量分别为:CC型(3.0±1.2)mg,CT型(3.0±1.2)mg,TT型(2.8±0.8)mg;各组间的剂量无统计学差异。NR1I2 7635G>A各基因型组的剂量分别为:GG型(2.7±1.0)mg,GA型(3.1±1.1)mg,AA型(3.1±1.4)mg;GA与AA型组的华法林维持剂量显著高于GG型(P<0.05)。结论 NR1I2 7635G>A突变后与华法林维持剂量上调相关,患者在制定个体化给药方案时应参考NR1I2 7635G>A基因型。

Impact of NR1I2 polymorphisms on warfarin maintenance dose and its inter-individual variation

OBJECTIVE To assess the impact of NR1I2 polymorphisms on the warfarin maintenance dose in Chinese patients with heart valve replacement(HVR).METHODS One hundred and seventy-nine Han Chinese HVR patients were recruited.Polymorphisms of NR1I2-25385 C>T and NR1I2 7635 G>A were detected by direct sequencing.VKORC1-1639 G>A and CYP2C9*3 were genotyped using the polymerase chain reaction restriction fragment length polymorphism method(PCR-RFLP).International normalized ratio(INR) and warfarin maintenance doses were obtained from patients′ medical records.RESULTS The mutation frequency of NR1I2-25385 C>T was CC 62.6%,CT 31.3% and TT 6.1%,respectively,and mutation frequency of NR1I2 7635 G>A was GG 30.7%,GA 49.2% and AA 20.1%.The warfarin maintenance dose of NR1I2-25385 C>T was CC(3.0±1.2)mg,CT(3.0±1.2)mg and TT(2.8±0.8)mg.No significant statistical difference was found.The warfarin maintenance dose of NR1I2 7635 G>A was GG(2.7±1.0)mg,GA(3.1±1.1)mg,AA(3.1±1.4)mg.NR1I2 7635 GA/AA group presented a significantly higher warfarin maintenance dose than GG group(P<0.05).CONCLUSIONNR1I2 7635 G>A is another minor but significant genetic factor contributed to the inter-individual variability of warfarin maintenance dose.