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

PLoS One

Tia Aalto-Viljakainen¹  Hannele Laivuori²  A. Inkeri Lokki²  Seppo Meri³ 

[1] Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland;Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland;Immunobiology research program, Research Programs Unit, University of Helsinki, Helsinki, Finland

关键词: Preeclampsia;    Complement system;    Proteinuria;    Hypertensive disorders in pregnancy;    Pregnancy;    Blood pressure;    Cofactors (biochemistry);    Regulator genes;   

DOI  :  10.1371/journal.pone.0117840

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY