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。
Abstract
OBJECTIVE To conduct a retrospective cohort study and determine the influence of the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene alleles on over anticoagulation and bleeding complication in Chinese population. METHODS Patients who underwent heart valve replacement operation in Cardiovascular Surgery of Fujian Provincial Hospital between January 2011 and August 2013 were included, who took warfarin at least 3 months and whose INR level was controlled between 1.8 and 2.5. Genotypes of VKORC1-1639 G>A were tested by polymerase chain reaction (PCR) - gene sequencing technique. SPSS19.0 software was used to analyze the association between genotypes andwarfarin bleeding complications, adjusted for demographic and clinical factors. RESULTS Totally 196 patients were included, mean age (50.8±10.7) years, 80 males, average follow-up (26.9±11.8) months. Of the 434 patient-year, 18 severe bleeding and 59 minor bleeding occurred in 31patients. Patients with VKORC1-1639 AA were associated with higher bleeding risk than G carriers(HR 3.14;95% CI: 1.14-8.68). Meanwhile, Kaplan-Meier survival curve showed that time to bleeding evens of VKORC1-1639 AA carriers was shorter than G-carriers(Log-rank test, P=0.03). CONCLUSION VKORC1-1639 G>A might be the major predictive factor of bleeding complication for warfarin therapy in Chinese patients.
关键词
华法林 /
VKORC1 /
出血 /
多态现象
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Key words
warfarin /
VKORC1 /
hemorrhagic complication /
polymorphism
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参考文献
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脚注
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基金
全国临床重点专科项目(心脏大血管外科)(2013)资助;国家临床重点学科建设项目(国卫办送函544号)
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