Abstract
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 complement system has been suggested to predispose women to preeclampsia. Complement is part of the innate and adaptive immune systems and potentially capable of causing inflammation 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 in CD46 predispose to thrombotic microangiopathy with endothelial cell dysfunction. The exome of CD46 were sequenced 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 previous 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 other CD46 SNPs and preeclampsia. This study describes a carefully characterized cohort of severely preeclamptic Finnish women and found no potentially predisposing variants in CD46. However, it is possible that other genetic components of the complement system may affect the pathogenesis of severe preeclampsia and related diseases.
Highlights
Preeclampsia is a common (3–5%) disorder of pregnancy
Preeclamptic patients with heavy proteinuria were selected for the project, because several previous studies pointed towards functional problems of the kidney in association with complement activation and with CD46 mutations, as observed in atypical hemolytic uremic syndrome (aHUS) [17,21,22,32]
In the PROMISSE cohort consisting of 250 pregnant patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibody (APL Ab) syndrome they found an increase from 2.5% to 7% in A304V heterozygosity in women, who developed preeclampsia
Summary
The objective of this study was to investigate whether sequence variations in the CD46 promoter, splice sites and exome are present in Finnish women with and without preeclampsia
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