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The causes of pre-eclampsia (PE) remain enigmatic, but there is a genetic component. The diagnosis probably covers several conditions but it is, in any case, a multifactorial disease; there will not be a single ‘PE gene’, but interactions between several genes, and between them and the environment, may predispose to it. Several polymorphisms of genes involved in the clotting cascade may predispose to PE, but are not pre-requisites. Among these are the polymorphisms Factor V Leiden and C677T methylenetetrahydrofolate reductase (MTHFR); both have functional consequences. In some, but not all, populations, there is an increased frequency of the M235T variant of the angiotensinogen gene in women with PE. However, this polymorphism also has an increased incidence in essential hypertension and coronary heart disease. There is significantly distorted maternal–fetal transmission of a dinucleotide repeat polymorphism of the angiotensinogen gene in PE, associated with low plasma-angiotensinogen concentrations, and of a similar polymorphism in the Type 1 angiotensin receptor. There is no evidence at present for a genetic involvement of the HLA system. The complex nature of PE means that large-scale studies of carefully-phenotyped women will be needed to unravel the genetic contribution to its pathogenesis. Such a study is just beginning in the UK (the GOPEC study).
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