title: Genetic analysis of membrane cofactor protein (CD46) of the complement system in women with and without preeclamptic pregnancies.
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.
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland; Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland; Immunobiology research program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
authors.forename: A Inkeri
authors.initials: AI
authors.lastname: Lokki
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland; Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tia
authors.initials: T
authors.lastname: Aalto-Viljakainen
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland; Immunobiology research program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland; Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Hannele
authors.initials: H
authors.lastname: Laivuori
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism*; D059472:Exome / Q000235:genetics; D005091:Exons; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D051916:Membrane Cofactor Protein / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index
chemical_list: D051916:Membrane Cofactor Protein; D003165:Complement System Proteins