GENETICS OF PREECLAMPSIA

Pre-eclampsia is a serious complication of the second half of human pregnancy which occurs at frequencies of 1% to 5% in most parts of the world. It is characterized clinically by high blood pressure, proteinuria, and generalized edema in association with a wide range of pathophysiological organ and system disturbances. Untreated, it can lead to the occurrence of epileptic-like grandmal convulsions (eclampsia), which is a source of considerable maternal and fetal morbidity. The disease is unusual in having no known cause, although an immunological impairment is suspected. Here we review the evidence that the condition is genetic in origin. Several genetic models are discussed, Markedly raised incidences are seen in blood relatives (mothers, daughters, sisters, and granddaughters) but not in relatives by marriage (daughters-in-law, mothers-in-law). This suggests that the condition is caused by maternal genes. Other evidence, however, implicates the fetal genotype. The most decisive data supporting this show a lack of concordance in monozygous twins. Thus the condition may be the result of a maternal-fetal genotype by genotype interaction, broadly analogous to Rhesus disease. To date, most attempts to find the genes involved have focused on the human leucocyte antigen (HLA) system. It is clear that the maternal genes are not in the HLA system, but the possibility that the postulated fetal genes are located there remains open. Current work concentrates on linkage studies aimed at finding the responsible genes. There is still a need for more pedigree and twin data, especially from non-European ethnic groups.