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Thrombophilic polymorphisms in pre-eclampsia: altered frequency of the functional 98C>T polymorphism of glycoprotein IIIa
  1. Kevin M O'Shaughnessya,
  2. Beiyuan Fua,
  3. Sarah Downinga,
  4. Nicholas H Morrisb
  1. aClinical Pharmacology Unit, Department of Medicine, University of Cambridge Clinical School, Cambridge, UK, bAcademic Department of Obstetrics and Gynaecology, Chelsea and Westminster Hospital and North London Hospitals Trust, London, UK
  1. Dr O'Shaughnessy, Clinical Pharmacology Unit, Level 6 ACCI, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK,kmo22{at}medschl.cam.ac.uk

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Editor—Pre-eclampsia is a heritable endothelial disorder, which is unique to pregnancy1 and characteristically associated with haemostatic and thrombophilic abnormalities. This association has led to the identification of a number of gene variants that might confer thrombophilic risk in pre-eclampsia. An increased carrier rate for two of these polymorphisms, factor V Leiden2 and the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR),3has been reported in some women with pre-eclampsia. However, we have been unable to replicate these findings in our own East Anglian population.4

We have now looked at two further candidate thrombophilic polymorphisms in our pre-eclampsia cohort that are involved in the regulation of vascular thrombosis. The first is the 20210G>A polymorphism in the 3′ UTR region of the prothrombin (PT) gene that causes a modest rise in plasma prothrombin levels,5 and is reportedly associated with severe pre-eclampsia in an Israeli cohort.6 The second is a coding variant (98C>T) in exon 2 of theGPIIIa gene that provides the common beta subunit for several β3-integrins including the platelet fibrinogen receptor. This polymorphism causes a 33Leu>Pro substitution and the existence of two antigenically distinct forms of the mature GPIIb/IIIa antigen on platelets (the Pl(A) antigens 1 and 2). Loss of functional GPIIIa is associated with a rare bleeding disorder (Glanzmann's thrombasthenia) and the 33Pro variant itself has been associated with risk of premature acute coronary syndromes and stroke in young white women.7

Materials and methods

The method of recruitment and the definition of pre-eclampsia used in our cohort have been published previously.4 In brief, they all had proteinuric pregnancy related hypertension as defined by the criteria of Redman and Jefferies.8 The local ethics committee approved the study and all patients gave written informed consent before taking part. At the time of this study, we …

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