Mrozikiewicz P M, Cascorbi I, Ziemer S, Laule M, Meisel C, Stangl V, Rutsch W, Wernecke K, Baumann G, Roots I, Stangl K
Institute of Clinical Pharmacology, Charité University Medical Center, Humboldt University of Berlin, Germany.
J Am Coll Cardiol. 2000 Nov 1;36(5):1520-5. doi: 10.1016/s0735-1097(00)00925-6.
We have focused on the role of coagulation factor VII (FVII) Arg353Gln polymorphism as a risk predictor of complications following percutaneous transluminal coronary angioplasty (PTCA), directional coronary atherectomy (DCA), and stenting.
The FVII Arg353Gln mutation decreases FVII activity, and presence of the Gln353 allele could be protective against thrombus formation during catheter interventions.
A total of 666 consecutive patients with coronary artery disease who had undergone PTCA (n = 280), DCA (n = 104), or stenting (n = 282) were followed up for a 30-day composite end point, which included need for target vessel revascularization, myocardial infarction, and death. The Arg353Gln polymorphism of FVII was determined by PCR/RFLP assay.
Carriers of the Gln353 allele had significantly lower levels of total FVII activity (FVIIc, -20.7%, p < 0.001) and of activated circulating FVII (FVIIa, -32.7%, p = 0.03) compared with Arg353/Arg353. The composite end point occurred in 43 patients: 4 were heterozygous Arg353/Gln353, and 39 were homozygous Arg353/Arg353. The incidence of the composite end point was 2.5% in carriers of the Gln353 allele and 7.7% in Arg353/Arg353 homozygotes (p = 0.013). This corresponds to a 72% risk reduction in carriers of the Gln353 allele (relative risk: 0.28; 95% confidence interval: 0.09-0.81; p = 0.02).
The Gln353 allele of FVII is associated with substantial risk reduction in adverse events that complicate coronary catheter interventions. With the perspective of active site-blocked activated FVII (FVIIai) as conjunctive medication, the results suggest that the FVII genotype should be taken into due consideration in assessment of FVIIai medication and of its dosage.
我们重点研究了凝血因子VII（FVII）Arg353Gln多态性作为经皮腔内冠状动脉成形术（PTCA）、定向冠状动脉粥样斑块切除术（DCA）和支架置入术后并发症风险预测指标的作用。
FVII Arg353Gln突变会降低FVII活性，Gln353等位基因的存在可能对导管介入治疗期间的血栓形成具有保护作用。
对总共666例接受PTCA（n = 280）、DCA（n = 104）或支架置入术（n = 282）的冠心病连续患者进行随访，观察30天综合终点事件，包括靶血管血运重建需求、心肌梗死和死亡。通过PCR/RFLP分析确定FVII的Arg353Gln多态性。
与Arg353/Arg353相比，Gln353等位基因携带者的总FVII活性（FVIIc，降低20.7%，p < 0.001）和活化循环FVII（FVIIa，降低32.7%，p = 0.03）水平显著降低。43例患者出现了综合终点事件：4例为Arg353/Gln353杂合子，39例为Arg353/Arg353纯合子。Gln353等位基因携带者的综合终点事件发生率为2.5%，Arg353/Arg353纯合子为7.7%（p = 0.013）。这相当于Gln系列等位基因携带者的风险降低了72%（相对风险：0.28；95%置信区间：0.09 - 0.81；p = 0.02）。
FVII的Gln353等位基因与降低冠状动脉导管介入治疗相关不良事件的风险显著相关。鉴于活性位点阻断的活化FVII（FVIIai）作为联合用药，研究结果表明在评估FVIIai用药及其剂量时应充分考虑FVII基因型。
