RESEARCH ARTICLE Genetic Analysis of Membrane Cofactor Protein (CD46) of the Complement System in Women with and without Preeclamptic

Preeclampsia is a common disorder of pregnancy characterized by endothelial dysfunction. It may be life-threatening for the mother and fetus in severe cases. Dysregulation of the com-plement system has been suggested to predispose women to preeclampsia. Complement is part of the innate and adaptive immune systems and potentially capable of causing inflam-mation and tissue damage. Membrane cofactor protein MCP (CD46) is among the potent complement regulators that have recently been linked to a severe form of preeclampsia with or without an underlying autoimmune phenotype. Mutations inCD46 predispose to throm-botic microangiopathy with endothelial cell dysfunction. The exome of CD46were se-quenced in 95 Finnish women with severe preeclampsia. Genetic variations discovered in the full exome were compared to those observed in 95 control women who did not develop preeclampsia. Because A304V (rs35366573) was associated with preeclampsia in one pre-vious study, we sequenced the transmembrane region including the A304V variant and part of the cytoplasmic tail in 95 additional controls. We did not discover any association between A304V or otherCD46 SNPs and preeclampsia. This study describes a carefully character-ized cohort of severely preeclamptic Finnish women and found no potentially predisposing variants inCD46. However, it is possible that other genetic components of the complement systemmay affect the pathogenesis of severe preeclampsia and related diseases