Gori Anna Maria, Marcucci Rossella, Fatini Cinzia, Gensini Francesca, Sticchi Elena, Sodi Andrea, Cappelli Stefania, Menchini Ugo, Gensini Gian Franco, Abbate Rosanna, Prisco Domenico
Department of Surgical and Medical Critical Care, Thrombosis Center, University of Florence, Viale Morgagni, 85, 50134 Florence, Italy.
Thromb Haemost. 2004 Jul;92(1):54-60. doi: 10.1160/TH03-08-0509.
Few and contrasting data are available on the presence of a thrombophilic state in patients with retinal vein occlusion (RVO), and we have previously demonstrated a role of elevated PAI-1 activity as a risk factor for this condition. The present study was undertaken to investigate whether PAI 4G/5G and ACE I/D polymorphisms are independent risk factors for RVO and whether they account for elevated PAI-1 activity levels. We studied 112 RVO patients (52 males and 60 females; range 18-83 years; median age 60 years) and 112 healthy subjects (52 males and 60 females; range 20-84 years; median age 57 years). PAI-1 activity was determined by a chromogenic assay and ACE I/D and PAI-1 4G/5G polymorphisms by polymerase chain reaction (PCR) and restriction length fragment polymorphism (RLFP) methods. Elevated PAI-1 activity (above 95(th) percentile of the controls) was significantly associated with RVO at multivariate analysis after adjustment for age, sex, traditional cardiovascular risk factors and haemostasis-related risk factors (OR = 4.93, 95% CI 1.70-14.30; p = 0.003). The homozygosity for ACE DD was found to be an independent risk factor for RVO at multivariate analysis (OR = 1.98, 95% CI 1.01-3.83; p = 0.049), whereas no significant association between homozygosity for PAI-1 4G4G and risk of RVO was observed. Subjects carrying both ACE DD genotype and PAI-1 4G4G genotype showed an increased risk for RVO at multivariate analysis (OR = 4.82, 95% CI 1.89-12.29; p = 0.001). In 45/112 patients without the established risk factors for RVO (hyper-tension, hypercholesterolemia and diabetes) or characteristics known to be associated to increased PAI-1 activity (overweight, hypertriglyceridemia, and smoking habit) the contemporary presence of ACE DD and PAI-1 4G4G genotype was significantly associated with a risk for RVO (OR = 8.26, 95% CI 1.18-57.92; p = 0.034). In conclusion, in our study: 1-indicates that ACE DD genotype is a risk factor for RVO in the whole group of patients, and in the subgroup of patients without the established risk factors for RVO or characteristics influencing the PAI-1 activity, when associated to PAI-1 4G4G genotype, and 2-confirms the role of hypofibrinolysis, documented by high levels of PAI-1 activity, in the occurrence of patients with RVO.
关于视网膜静脉阻塞（RVO）患者血栓形成倾向状态的现有数据很少且相互矛盾，我们之前已经证明纤溶酶原激活物抑制剂-1（PAI-1）活性升高是该疾病的一个危险因素。本研究旨在调查PAI 4G/5G和血管紧张素转换酶（ACE）I/D多态性是否为RVO的独立危险因素，以及它们是否与PAI-1活性水平升高有关。我们研究了112例RVO患者（52例男性和60例女性；年龄范围18 - 83岁；中位年龄60岁）和112例健康受试者（52例男性和60例女性；年龄范围20 - 84岁；中位年龄57岁）。通过发色底物法测定PAI-1活性，采用聚合酶链反应（PCR）和限制性片段长度多态性（RLFP）方法检测ACE I/D和PAI-1 4G/5G多态性。在对年龄、性别、传统心血管危险因素和止血相关危险因素进行调整后的多因素分析中，PAI-1活性升高（高于对照组第95百分位数）与RVO显著相关（比值比[OR]=4.93，95%可信区间[CI] 1.70 - 14.30；P = 0.003）。在多因素分析中，ACE DD纯合子被发现是RVO的独立危险因素（OR = 1.98，95% CI 1.01 - 3.83；P = 0.049），而未观察到PAI-1 4G4G纯合子与RVO风险之间存在显著关联。在多因素分析中，同时携带ACE DD基因型和PAI-1 4G4G基因型的受试者RVO风险增加（OR = 4.82，95% CI 1.89 - 12.29；P = 0.001）。在112例无RVO既定危险因素（高血压、高胆固醇血症和糖尿病）或已知与PAI-1活性增加相关特征（超重、高甘油三酯血症和吸烟习惯）的患者中，ACE DD和PAI-1 4G4G基因型同时存在与RVO风险显著相关（OR = 8.26，95% CI 1.18 - 57.92；P = 0.034）。总之，在我们的研究中：1-表明ACE DD基因型在整个患者组中是RVO的危险因素，在无RVO既定危险因素或影响PAI-1活性特征的患者亚组中，与PAI-1 4G4G基因型相关时是RVO的危险因素；2-证实了PAI-1活性高水平所证明的低纤溶状态在RVO患者发病中的作用。
