摘要:
目的 探讨VKORC1基因1639G/A位点多态性与心房颤动(简称房颤)患者抗凝治疗及左房血栓的相关性.方法 回顾性选取2015年5月至2016年5月上海市第十人民医院收治的100例非瓣膜性心脏病房颤患者作为实验组,选取同期来同济大学附属普陀人民医院进行体检的100例正常无房颤患者作为对照组.清晨空腹采集对照组和实验组的血液2ml,应用PCR芯片杂交法测定VKORC1-1639AA/GA/GG的基因型,比较不同基因型的房颤患者抗凝达标后华法林维持剂量的差异情况,并通过经食管超声心动图检查观察房颤患者左房血栓的位置、大小及抗凝治疗前后血栓变化情况.结果 实验组VKORC1-1639AA型占83%,GA型占15%,GG型占2%,对照组中VKORC1-1639AA型占81%,GA型占14%,GG型占5%.实验组和对照组在AA、GA、GG3种基因型方面,差异并无统计学意义(P>0.05),A、G等位基因频率差异亦无统计学意义(P>0.05).VKORC1-1639AA患者对华法林更加敏感,AA患者达到国际标准化比值稳定浓度的华法林维持剂量比GA、GG者小.非瓣膜性心脏病房颤患者左房增大对左心耳的血栓形成有预测价值;左房内径越大者,血栓检出率越高.2例VKORC1-1639GG者经食管超声心动图检查均发现左房血栓,且经华法林抗凝血治疗国际标准化比值达标后血栓大小无明显变化.结论 VKORC11639G/A基因位点多态性与人群是否罹患房颤无相关性,基因分型以AA型多见,对华法林更敏感;经食管超声心动图检查发现房颤者左房更大,血栓多位于左心耳,服用华法林抗凝治疗且国际标准化比值达标后复查经食管超声心动图检查,左心耳血栓消失多见,基因型为GG型的房颤患者均发现左房血栓,但国际标准化比值达标前后血栓无明显变化.%Objective To explore the relationship between the polymorphism of VKORC1 gene 1639G/A with anticoagulant therapy for left atrial thrombi in patients with atrial fibrillation. Methods A total of 100 patients with non-valvular atrial fibrillation in this hospital during May 2015 to May 2016 were retrospectively selected as experimental group. 100 healthy persons for physical examination in this hospital at the same period were selected as control group. Two milliliters of fasting venous blood of all subjects were collected,and the genotypes of VKORC1-1639 AA/GA/ GG were determined by PCR chip hybridization. To maintain the dosage difference in warfarin,and through the transesophageal echocardiography to observe the location of atrial thrombus,size and anticoagulant change before and after thrombosis in patients with atrial fibrilla-tion. Results VKORC1-1639 AA type accounted for 83%,GA type accounted for 15%,GG type accounted for 2%,VKORC1-1639 AA type accounted for 81%,GA type accounted for 14%,and GG type accounted for 5% . There was no significant difference in genotypes of AA, GA and GG between experimental group and control group (P>0.05). There was no significant difference in frequencies of A and G alleles (P>0.05). Patients with VKORC1-1639 AA were more susceptible to warfarin,and warfarin in patients with AA in stable concentrations with internationally standardized ratio maintain a lower maintenance dosage than those with GA and GG. Patients with left atrial enlargement of left atrial appendage thrombosis without valvular atrial fibrillation had predictive value;the larger of left atrial diameter was,the higher rate of thrombus de-tection would be. The VKORC1-1639 GG transesophageal echocardiography in 2 cases showed left atrial thrombus,and warfarin anticoagulant treatment with international standardization ratio reached,the thrombus size did not significantly. change. Conclusion There is no correlation be-tween polymorphism of VKORC11639G/A locus and atrial fibrillation in human population. Genotype AA is more common in genotypes and more sensitive to warfarin. The transesophageal echocardiography showed that the larger left atrium is,more thrombi in the left atrial appendage are, warfarin anticoagulation therapy and the international standardization ratio after the re-examination of transesophageal echocardiography,thrombo-sis in left atrial appendage is more common,and atrial fibrillation in patients with genotype GG are usually found left atrial thrombus. However, before and after the reach of international standardization ratio,the thrombosis has no significant change.