OBJECTIVE To assess the impact of NRII2 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 NR112 - 25385 C > T was CC62.6%, CT31.3% and TT6.1%, 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 ±l.l)mg, AA (3. 1 ±1.4)mg. NR1I21635 GA/AA group presented a significantly higher warfarin maintenance dose than GG group (P A is another minor but significant genetic factor contributed to the inter-individual variability of warfarin maintenance dose.%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%和从型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,从型(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.
展开▼