KL 39 Update on genetics in preeclampsia

Abstract

Pre-eclampsia is a key challenge in all levels of obstetric care, because the onset and clinical course is unpredictable. The public health impact of pre-eclampsia is not limited to the obstetric and pediatric domains. It is also associated with increased risk of cardiovascular diseases in later life of the mother and the offspring. Pre-eclampsia has its origins in early pregnancy long before the onset of clinical disease. Risk prediction tools, including sequence variants, to predict pre-eclampsia and its subgroups in early pregnancy would be a major advance in healthcare. The use of genetic profiling has the advantage of being a primary factor, unchanged by pregnancy or disease processes. The contribution of maternal and fetal (paternal) genotypes needs to be taken into consideration. The InterPregGen study has assembled a consortium of researchers from Europe, Central Asia and South America with the aim of identifying sequence variants in the genome of mothers and/or offspring affected by pre-eclampsia. The consortium has reported the discovery of the first genome-wide significant susceptibility locus in the offspring from pre-eclamptic pregnancies. The locus is near the fms-related tyrosine kinase gene(FLT1) encoding fms-like tyrosine kinase 1 implicated in pre-eclampsia. There might be advantages for studying the role of rare variation in pre-eclampsia in founder populations. Genotype-phenotype relationships can be further studied combining genetic data and health data from population registries. In a targeted exome sequencing study we have found maternal low-frequency variants in FLT1 that may protect from pre-eclampsia. These variants are enriched in a Finnish population and may also protect from heart failure in later life. Any new gene discovery will highlight a known pathway or reveal a new biochemical pathway in the pathogenic process leading to pre-eclampsia and may also help identifying individuals with higher risk for later cardiovascular disease.