因子vr2单倍型和常见血栓标志物作为缺血性卒中遗传危险因素的作用

M. Michele, S. Lorenzano, N. Angelosanto, A. Serrao, L. Petraglia, A. Risitano, D. Toni, A. Chistolini
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Homocysteinemia was assessed within 48 hours and after 30 days from stroke onset. Univariate and multivariate analyses were performed. Results: Compared with controls, patients were significantly older (mean [SD] age, 50.5 [12.9] vs 37.5 [15.5] years, P < .001), less frequently females (48.1% vs 67.7%, P = .001) and had more frequently hyperhomocysteinemia (45.9% vs 11.0%) only in the acute phase (OR 6.899, CI 95% 2.993-15.899; P < .001). No differences were found in the prevalence of FV Leiden, PTH G20210A, and MTHFR C677T between patients and controls, whereas FVHR2 was present in 34/156 (22%) stroke patients and in 5/124 (4%) controls (OR 6.632, 95% CI 2.509-17.535, P < .001). In a multivariate logistic regression analysis, the FVHR2 resulted independently associated with the occurrence of IS (OR 6.071, 95% CI 1.762-20.923; P = .004). Conclusions: In our study, hyperhomocysteinemia was confirmed to be a transient consequence of the thrombotic event. 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摘要

背景:常见血栓形成标志物作为缺血性卒中(IS)风险决定因素的作用仍不确定。FV基因中的His1299Arg多态性被称为R2单倍型(FVHR2),目前对其多态性研究较少。本研究的目的是评估IS患者队列中常见血栓形成标志物和FVHR2的患病率,并与非匹配组的健康个体进行比较。方法:我们研究了156例首次IS的连续幸存者和124例健康对照。检测所有受试者的基因多态性因子V (FV) Leiden、凝血酶原(PTH) G20210A、MTHFR C677T和FVHR2。测定蛋白C (PC)、蛋白S (PS)、抗凝血酶(ATIII)和狼疮抗凝血剂(LAC)活性。同型半胱氨酸血症在中风发作后48小时内和30天后进行评估。进行单因素和多因素分析。结果:与对照组相比,患者明显变老(平均[SD]年龄,50.5 [12.9]vs 37.5[15.5]岁,P < .001),女性较少(48.1% vs 67.7%, P = .001),高同型半胱氨酸血症仅在急性期更频繁(45.9% vs 11.0%) (OR 6.899, CI 95% 2.993-15.899;P < 0.001)。FV Leiden、PTH G20210A和MTHFR C677T的患病率在患者和对照组之间没有差异,而FVHR2在34/156(22%)脑卒中患者和5/124(4%)脑卒中对照组中存在(OR 6.632, 95% CI 2.505 -17.535, P < 0.001)。在多因素logistic回归分析中,FVHR2结果与IS的发生独立相关(OR 6.071, 95% CI 1.762-20.923;P = .004)。结论:在我们的研究中,高同型半胱氨酸血症被证实是血栓事件的短暂后果。在意大利样本人群中,无论年龄和性别,FVHR2似乎都是与动脉IS相关的可能的候选血栓前病变。
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Role of Factor V R2 Haplotype and Common Thrombophilia Markers as Genetic Risk Factors for Ischemic Stroke
Background: Uncertainties remain about the role of common thrombophilia markers as determinants of the ischemic stroke (IS) risk. Polymorphism His1299Arg in the FV gene, named R2 haplotype (FVHR2), has been poorly investigated. The aim of the present study was to assess the prevalence of common thrombophilia markers and of FVHR2 in a cohort of IS patients compared to a nonmatched group of healthy individuals. Methods: We studied 156 consecutive patients survivors of a first ever IS and 124 healthy controls. All subjects were investigated for the gene polymorphisms factor V (FV) Leiden, prothrombin (PTH) G20210A, MTHFR C677T, and FVHR2. Protein C (PC), protein S (PS), antithrombin (ATIII), and lupus anticoagulant (LAC) activity was measured. Homocysteinemia was assessed within 48 hours and after 30 days from stroke onset. Univariate and multivariate analyses were performed. Results: Compared with controls, patients were significantly older (mean [SD] age, 50.5 [12.9] vs 37.5 [15.5] years, P < .001), less frequently females (48.1% vs 67.7%, P = .001) and had more frequently hyperhomocysteinemia (45.9% vs 11.0%) only in the acute phase (OR 6.899, CI 95% 2.993-15.899; P < .001). No differences were found in the prevalence of FV Leiden, PTH G20210A, and MTHFR C677T between patients and controls, whereas FVHR2 was present in 34/156 (22%) stroke patients and in 5/124 (4%) controls (OR 6.632, 95% CI 2.509-17.535, P < .001). In a multivariate logistic regression analysis, the FVHR2 resulted independently associated with the occurrence of IS (OR 6.071, 95% CI 1.762-20.923; P = .004). Conclusions: In our study, hyperhomocysteinemia was confirmed to be a transient consequence of the thrombotic event. FVHR2 seems to be a possible candidate prothrombotic condition related to arterial IS irrespective of age and sex in an Italian sample population.
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