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

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 i...

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Autores principales: Lokki, A. Inkeri, Aalto-Viljakainen, Tia, Meri, Seppo, Laivuori, Hannele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339547/
https://www.ncbi.nlm.nih.gov/pubmed/25710174
http://dx.doi.org/10.1371/journal.pone.0117840
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author Lokki, A. Inkeri
Aalto-Viljakainen, Tia
Meri, Seppo
Laivuori, Hannele
author_facet Lokki, A. Inkeri
Aalto-Viljakainen, Tia
Meri, Seppo
Laivuori, Hannele
author_sort Lokki, A. Inkeri
collection PubMed
description 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.
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spelling pubmed-43395472015-03-04 Genetic Analysis of Membrane Cofactor Protein (CD46) of the Complement System in Women with and without Preeclamptic Pregnancies Lokki, A. Inkeri Aalto-Viljakainen, Tia Meri, Seppo Laivuori, Hannele PLoS One Research Article 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. Public Library of Science 2015-02-24 /pmc/articles/PMC4339547/ /pubmed/25710174 http://dx.doi.org/10.1371/journal.pone.0117840 Text en © 2015 Lokki et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lokki, A. Inkeri
Aalto-Viljakainen, Tia
Meri, Seppo
Laivuori, Hannele
Genetic Analysis of Membrane Cofactor Protein (CD46) of the Complement System in Women with and without Preeclamptic Pregnancies
title Genetic Analysis of Membrane Cofactor Protein (CD46) of the Complement System in Women with and without Preeclamptic Pregnancies
title_full Genetic Analysis of Membrane Cofactor Protein (CD46) of the Complement System in Women with and without Preeclamptic Pregnancies
title_fullStr Genetic Analysis of Membrane Cofactor Protein (CD46) of the Complement System in Women with and without Preeclamptic Pregnancies
title_full_unstemmed Genetic Analysis of Membrane Cofactor Protein (CD46) of the Complement System in Women with and without Preeclamptic Pregnancies
title_short Genetic Analysis of Membrane Cofactor Protein (CD46) of the Complement System in Women with and without Preeclamptic Pregnancies
title_sort genetic analysis of membrane cofactor protein (cd46) of the complement system in women with and without preeclamptic pregnancies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339547/
https://www.ncbi.nlm.nih.gov/pubmed/25710174
http://dx.doi.org/10.1371/journal.pone.0117840
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