ArticleBJOG : an international journal of obstetrics and gynaecology2023
Identification of complement factor H variants that predispose to pre-eclampsia: A genetic and functional study.
Article in BJOG : an international journal of obstetrics and gynaecology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Systematic review of the complement components as potential biomarkers of pre-eclampsia: pitfalls and opportunities.Frontiers in immunology · 2024Pooled it
- Observational
- Platelets link coagulation and complement in regulating murine placental vascular development.The Journal of clinical investigation · 2026Article
- Association of Complement Genetics with Outcomes in IgA Nephropathy.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- Functional Roles of the Complement Immune System in Cardiac Inflammation and Hypertrophy.International journal of molecular sciences · 2025Review
- Type I interferon exposure of an implantation-on-a-chip device alters invasive extravillous trophoblast function.Cell reports. Medicine · 2025Article
- A Review of Dietary and Lifestyle Management of Pre-Eclampsia and Postpartum Eclampsia.Preventive nutrition and food science · 2025Review
- Understanding rare genetic variants within the terminal pathway of complement system in preeclampsia.Genes and immunity · 2025Article
- Differential expression of complement Properdin and Factor H in the placentae and umbilical cords of mothers with Preeclampsia, Gestational Diabetes Mellitus and Recurrent Pregnancy Loss.Frontiers in immunology · 2025Article
- The role of complement in normal pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- The complement system in human pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- Thrombotic Microangiopathy in Pregnancy: Current Understanding and Management Strategies.Kidney international reports · 2024Review
- Rare variants in genes coding for components of the terminal pathway of the complement system in preeclampsia.Research square · 2024Article
- Pregnancy as a susceptible state for thrombotic microangiopathies.Frontiers in medicine · 2024Review
- Protective role of complement factor H against the development of preeclampsia.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
objectiveThe objective of the study was to investigate the role of genetic variants in complement proteins in pre-eclampsia.
designIn a case-control study involving 609 cases and 2092 controls, five rare variants in complement factor H (CFH) were identified in women with severe and complicated pre-eclampsia. No variants were identified in controls.
settingPre-eclampsia is a leading cause of maternal and fetal morbidity and mortality. Immune maladaptation, in particular, complement activation that disrupts maternal-fetal tolerance leading to placental dysfunction and endothelial injury, has been proposed as a pathogenetic mechanism, but this remains unproven. POPULATION: We genotyped 609 pre-eclampsia cases and 2092 controls from FINNPEC and the national FINRISK cohorts.
methodsComplement-based functional and structural assays were conducted in vitro to define the significance of these five missense variants and each compared with wild type.
main outcome measuresSecretion, expression and ability to regulate complement activation were assessed for factor H proteins harbouring the mutations.
resultsWe identified five heterozygous rare variants in complement factor H (L3V, R127H, R166Q, C1077S and N1176K) in seven women with severe pre-eclampsia. These variants were not identified in controls. Variants C1077S and N1176K were novel. Antigenic, functional and structural analyses established that four (R127H, R166Q, C1077S and N1176K) were deleterious. Variants R127H and C1077S were synthesised, but not secreted. Variants R166Q and N1176K were secreted normally but showed reduced binding to C3b and consequently defective complement regulatory activity. No defect was identified for L3V.
conclusionsThese results suggest that complement dysregulation due to mutations in complement factor H is among the pathophysiological mechanisms underlying severe pre-eclampsia.
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