The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion

Abstract

Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndromeFdisorders 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 groupFP 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 didFPo0.05. 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)F82.5 vs 50%, Po0.05. These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.

Retinal Vein Occlusion and Polymorphisms

“…GPIa geninde iki bağlantılı polimorfizm tanımlandı (C807T/ G873A). 807T polimorfizmi retinal ven oklüzyonu için bir risk faktörü olabileceği belirtildi [14]. Ancak sonraki çalışma sonuç-ları bununla çelişir şekilde anlamlı bir ilişki bulunamadı [15][16][17].…”

“…Protrombin geni G20210A mutasyonu ve platelet glikoprotein IIIa polimorfizm PlA2, tromboembolik hastalıklarla ilişkisi gösteril-miştir. Bununla birlikte hem protrombin gen G20210A mutasyonu hem de platelet glikoprotein IIIa polimorfizm PlA2, SRVT ile ilişkili bulunamadı [22]. Platelet glikoprotein Ia/IIa (GpIa/ IIa) platelet-kollajen etkileşimini etkileyen adhesion molekülü-dür.…”

The platelet glycoprotein Ia/IIa gene polymorphism C807T/C873A: a novel risk factor for retinal vein occlusion

“…I read with interest the paper by Dodson et al 1 They provide further insight into the molecular basis for retinal vein occlusion (RVO). However, I would like to make a couple of points; firstly, they offer no information on the racial distribution of the patient groups, as the genotypic difference between them may reflect a different racial make-up.…”

“…After an episode of endophthalmitis, an eye with preexisting diabetic retinopathy may experience rapid, asymmetrical progression in the severity of the retinopathy compared to the other (noninfected) eye. 1,2 Most of the previously reported cases had a history of diabetes mellitus of 12 years or more. 1,2 We report a similar occurrence in a patient with a much shorter (4-year) duration of diabetes.…”

“…1,2 Most of the previously reported cases had a history of diabetes mellitus of 12 years or more. 1,2 We report a similar occurrence in a patient with a much shorter (4-year) duration of diabetes.…”