Lokki A Inkeri, Aalto-Viljakainen Tia, Meri Seppo, Laivuori Hannele
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.
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.
PLoS One. 2015 Feb 24;10(2):e0117840. doi: 10.1371/journal.pone.0117840. eCollection 2015.
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.
子痫前期是一种以血管内皮功能障碍为特征的常见妊娠疾病。在严重情况下，它可能对母亲和胎儿构成生命威胁。补体系统失调被认为会使女性易患子痫前期。补体是固有免疫系统和适应性免疫系统的一部分，有可能引发炎症和组织损伤。膜辅因子蛋白MCP（CD46）是最近与伴有或不伴有潜在自身免疫表型的严重子痫前期相关的强效补体调节因子之一。CD46突变易导致伴有内皮细胞功能障碍的血栓性微血管病。对95名患有严重子痫前期的芬兰女性的CD46外显子进行了测序。将在全外显子中发现的基因变异与95名未患子痫前期的对照女性中观察到的变异进行比较。由于在之前的一项研究中A304V（rs35366573）与子痫前期相关，我们对另外95名对照者的包括A304V变异体的跨膜区域和部分胞质尾进行了测序。我们未发现A304V或其他CD46单核苷酸多态性与子痫前期之间存在任何关联。这项研究描述了一组经过仔细特征分析的患有严重子痫前期的芬兰女性队列，未在CD46中发现潜在的易感变异。然而，补体系统的其他遗传成分可能会影响严重子痫前期及相关疾病的发病机制。
