ArticleProceedings of the National Academy of Sciences of the United States of America2011
Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
129 citing papers in PubMed, 2 syntheses or guidelines pooled it, 225 citations in OpenAlex.
- Complement factor H Val62Ile variant and risk of age-related macular degeneration: a meta-analysis.Molecular vision · 2013Pooled it
- The association between complement component 2/complement factor B polymorphisms and age-related macular degeneration: a HuGE review and meta-analysis.American journal of epidemiology · 2012Pooled it
- Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection.Frontiers in immunology · 2021Trial
- GOLDEN: Efficacy and Safety of Complement Factor B Antisense, Sefaxersen, in Geographic Atrophy due to Age-Related Macular Degeneration.Ophthalmology science · 2026Article
- Review
- From Retina to Vasculature: Oxidative Stress as a Common Mechanistic Link Between Age-Related Macular Degeneration and Cardiovascular Disease.Antioxidants (Basel, Switzerland) · 2026Review
- Advances in Complement Research: from Pathophysiology to Precision Medicine.Physiology (Bethesda, Md.) · 2026Review
- Complement Activation in Maternal and Placental Pathology of Preeclampsia.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Association of Carboxypeptidase B2 Gene Polymorphisms With Graft Loss in Kidney Transplantation.Transplantation direct · 2026Article
- Primary membranoproliferative glomerulonephritis: natural history, pathogenesis, and treatment.Frontiers in nephrology · 2026Review
- Common and rare variants in complement genes as biomarkers of COVID-19 infection and severity. A lesson to learn for emerging pathogens.Frontiers in immunology · 2026Article
- The role of complement in long COVID pathogenesis.JCI insight · 2025Review
- Knowing the enemy: strategic targeting of complement to treat Alzheimer disease.Nature reviews. Neurology · 2025Review
- Chronic kidney disease enhances alternative pathway activity: a new paradigm.The Journal of clinical investigation · 2025Review
- Relationship of gene polymorphisms for complement components C3 and factor H and kidney allograft function.BMC nephrology · 2025Observational
- Canonical and non-canonical roles of complement in atherosclerosis.Nature reviews. Cardiology · 2024Review
- Role of Complement in Liver Diseases.Seminars in liver disease · 2024Review
- Nanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts.ACS nano · 2024Article
- Proteomics and Microbiota Conjoint Analysis in the Nasal Mucus: Revelation of Differences in Immunological Function inAnimals : an open access journal from MDPI · 2024Article
- Genetic factors associated with age-related macular degeneration modulating plasma inflammatory biomarker levels in patients with AIDS.Ophthalmic genetics · 2024Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Common polymorphisms in complement alternative pathway (AP) proteins C3 (C3(R102G)), factor B (fB(R32Q)), and factor H (fH(V62I)) are associated with age-related macular degeneration (AMD) and other pathologies. Our published work showed that fB(R32Q) influences C3 convertase formation, whereas fH(V62I) affects factor I cofactor activity. Here we show how C3(R102G) (C3S/F) influences AP activity. In hemolysis assays, C3(102G) activated AP more efficiently (EC(50) C3(102G): 157 nM; C3(102R): 191 nM; P < 0.0001). fB binding kinetics and convertase stability were identical, but native and recombinant fH bound more strongly to C3b(102R) (K(D) C3b(102R): 1.0 μM; C3b(102G): 1.4 μM; P < 0.0001). Accelerated decay was unaltered, but fH cofactor activity was reduced for C3b(102G), favoring AP amplification. Combining disease "risk" variants (C3(102G), fB(32R), and fH(62V)) in add-back assays yielded sixfold higher hemolytic activity compared with "protective" variants (C3(102R), fB(32Q), and fH(62I); P < 0.0001). These data introduce the concept of a functional complotype (combination of polymorphisms) defining complement activity in an individual, thereby influencing susceptibility to AP-driven disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.