Dodson P M, Haynes J, Starczynski J, Farmer J, Shigdar S, Fegan G, Johnson R J, Fegan C
Department of Medical Ophthalmology Heartlands Hospital Bordesley Green East Birmingham B9 5SS, UK.
Eye (Lond). 2003 Aug;17(6):772-7. doi: 10.1038/sj.eye.6700452.
Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndrome-disorders known to contribute to both arterial and venous thrombosis. In both of these conditions and RVO, platelet activation occurs. Aspirin, not warfarin, is the most effective antithrombotic agent in RVO and, taken together, these observations suggest an important role for platelets in this common ocular thrombotic condition. Platelet glycoprotein Ia/IIa (GpIa/IIa) is an adhesion molecule mediating platelet-collagen interactions and is key to the initiation of thrombosis. Recently, the cellular density of this molecule was shown to be determined by two silent, linked polymorphisms (C807T/G873A) within the GpIa/IIa gene. There is evidence that some of the resulting genotypes are associated with thrombo-embolic disease. This study therefore aimed to establish the prevalence of the GpIa/IIa polymorphisms and the three commonest hereditary thrombophilic disorders (prothrombin gene G20210A (PT) mutation, Factor V Leiden (FVL), and the thermolabile methylene tetrahydrofolate reductase C677T (MTHFR) mutation) in patients with RVO and normal controls. The GpIa/IIa polymorphisms and thrombophilic abnormalities were all identified using the polymerase chain reaction.Our results show that the frequency of the GpIa/IIa polymorphisms was similar in our normal control population to previously published series. Patients with RVO, however, had only a 10% (4/40) frequency of the lowest risk subtype (CC/GG) compared to 37.5% (15/40) in the control group-P 0.0039. The incidence of the PT, FVL, and MTHFR thrombophilic mutations was not different between the two groups, but interestingly none of the 7/40 RVO cases with a PT, FVL, or MTHFR mutation had the low-risk GpIa/IIa genotype while all but one of the controls did-P<0.05. Thus, 17.5% of RVO patients harboured more than one prothrombotic abnormality. The principal difference between the RVO and control group was the very high incidence of the intermediate-risk GpIa/IIa subtype (CT/GA)-82.5 vs 50%, P&<0.05. These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.
视网膜静脉阻塞（RVO）与高同型半胱氨酸血症及抗磷脂综合征相关，而这两种病症均已知会导致动静脉血栓形成。在这两种病症以及RVO中，均会发生血小板活化。阿司匹林而非华法林是RVO中最有效的抗血栓形成药物，综合这些观察结果表明血小板在这种常见的眼部血栓形成病症中发挥着重要作用。血小板糖蛋白Ia/IIa（GpIa/IIa）是一种介导血小板与胶原蛋白相互作用的黏附分子，是血栓形成起始的关键因素。最近，该分子的细胞密度已被证明由GpIa/IIa基因内两个沉默的连锁多态性（C807T/G873A）所决定。有证据表明，一些由此产生的基因型与血栓栓塞性疾病相关。因此，本研究旨在确定RVO患者和正常对照中GpIa/IIa多态性以及三种最常见的遗传性血栓形成倾向病症（凝血酶原基因G20210A（PT）突变、因子V莱顿（FVL）以及不耐热的亚甲基四氢叶酸还原酶C677T（MTHFR）突变）的患病率。使用聚合酶链反应对GpIa/IIa多态性和血栓形成倾向异常进行了全部鉴定。我们的结果表明，GpIa/IIa多态性在我们的正常对照人群中的频率与先前发表的系列研究相似。然而，RVO患者中最低风险亚型（CC/GG）的频率仅为10%（4/40），而对照组为37.5%（15/40），P = 0.0039。两组之间PT、FVL和MTHFR血栓形成倾向突变的发生率并无差异，但有趣的是，40名RVO患者中有7名携带PT、FVL或MTHFR突变，其中没有一人具有低风险的GpIa/IIa基因型，而对照组中除一人外均有此基因型，P<0.05。因此，17.5%的RVO患者存在不止一种促血栓形成异常。RVO组和对照组之间的主要差异在于中等风险的GpIa/IIa亚型（CT/GA）的发生率非常高，分别为82.5%和50%，P<0.05。这些结果表明GpIa/IIa多态性在RVO的发病机制中起主要作用。
