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目的采用回顾性队列研究方法,探讨VKORC1-1639G>A基因多态性与心脏瓣膜置换术后接受华法林治疗的患者出血并发症的影响。方法选择2011年1月~2013年8月在福建省立医院(下称“我院”)心血管外科行心脏瓣膜置换术的患者,采用聚合酶链式反应(polymerase chain reaction,PCR)-基因测序法检测患者的VKORC1-1639 G>A的基因型。采用SPSS19.0统计软件评估该基因型与出血并发症之间的关系。结果总共纳入196例患者,年龄(50.8±10.7)岁,男性80名,女性116名;平均累积随访(26.9±11.8)个月。在434人年中发生18例严重出血和59例轻度出血。VKORC1-1639 G>A基因型,AA等位基因增加总出血的风险(HR 3.14;95%CI:1.14~8.68),而没有增加轻度出血(HR 2.81;95%CI:0.80~9.93)、严重出血(HR 4.59;95%CI:0.86~24.48)的风险。对于VKORC1-1639 G>A基因型,Kaplan-Meier生存曲线显示,AA等位基因患者发生总出血事件所经过的时间比GG和GA等位基因患者显著缩短(Log-rank检验,P=0.03)。结论 VKORC1-1639 G>A纯合突变型携带者出血事件的风险增加。该基因可能是中国华法林抗凝治疗的患者出血并发症的主要遗传因素。
Objective To investigate the impact of VKORC1-1639G> A polymorphism on bleeding complications in patients receiving warfarin after heart valve replacement by retrospective cohort study. Methods From January 2011 to August 2013, patients undergoing cardiac valve replacement in the Department of Cardiovascular Surgery, Fujian Provincial Hospital (hereinafter referred to as “our hospital”) were recruited and analyzed by polymerase chain reaction (PCR) Genotypes of patients with VKORC1-1639 G> A were detected by gene sequencing. SPSS19.0 statistical software was used to assess the relationship between genotypes and bleeding complications. Results A total of 196 patients (50.8 ± 10.7 years) were enrolled, including 80 males and 116 females. The average cumulative follow-up was (26.9 ± 11.8) months. In 434 person-years 18 cases of severe bleeding and 59 cases of mild bleeding occurred. VKORC1-1639 G> A genotype, the AA allele increased the risk of total bleeding (HR 3.14; 95% CI: 1.14-8.68) without increasing mild bleeding (HR 2.81; 95% CI: 0.80-9.93) Severe bleeding (HR 4.59; 95% CI: 0.86 to 24.48). Kaplan-Meier survival curves for the VKORC1-1639 G> A genotype showed that patients with the AA allele had significantly shorter overall bleeding episodes than those with the GG and GA alleles (Log-rank test, P = 0.03) . Conclusion There is an increased risk of bleeding in VKORC1-1639 G> A homozygous mutant carriers. The gene may be warfarin anticoagulation in China in patients with bleeding complications of the main genetic factors.