ArticleAmerican journal of human genetics2012
Genetically determined partial complement C4 deficiency states are not independent risk factors for SLE in UK and Spanish populations.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Association between complement 4 copy number variation and systemic lupus erythematosus: a meta-analysis.Clinical and experimental medicine · 2020Pooled it
- Association of C4d with disease activity in anti-neutrophil cytoplasmic antibody-associated vasculitis: evidence for classical/lectin complement pathway activation.Arthritis research & therapy · 2025Article
- Exosomal-complement system activation in preeclampsia.The journal of obstetrics and gynaecology research · 2025Review
- Low C4A copy numbers and higher HERV gene insertion contributes to increased risk of SLE, with absence of association with disease phenotype and disease activity.Immunologic research · 2024Article
- Is the Complement System Dysregulated in Preeclampsia Comorbid with HIV Infection?International journal of molecular sciences · 2024Review
- The complement system and human autoimmune diseases.Journal of autoimmunity · 2023Review
- Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjögren's Syndrome.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Association between HLA alleles and sub-phenotype of childhood steroid-sensitive nephrotic syndrome.World journal of pediatrics : WJP · 2022Article
- Anaphylatoxins spark the flame in early autoimmunity.Frontiers in immunology · 2022Review
- Genetics in Behcet's Disease: An Update Review.Frontiers in ophthalmology · 2022Review
- Not all that is 'full house' is systemic lupus erythematosus: a case of membranous nephropathy due to syphilis infection.BMJ case reports · 2021Article
- Genes and Pseudogenes: Complexity of the RCCX Locus and Disease.Frontiers in endocrinology · 2021Review
- Complement C4, Infections, and Autoimmune Diseases.Frontiers in immunology · 2021Review
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- A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica.Nature communications · 2018Article
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- Association between C4, C4A, and C4B copy number variations and susceptibility to autoimmune diseases: a meta-analysis.Scientific reports · 2017Article
- Effects of Complement C4 Gene Copy Number Variations, Size Dichotomy, and C4A Deficiency on Genetic Risk and Clinical Presentation of Systemic Lupus Erythematosus in East Asian Populations.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease. Complete deficiency of complement component C4 confers strong genetic risk for SLE. Partial C4 deficiency states have also shown association with SLE, but despite much effort over the last 30 years, it has not been established whether this association is primarily causal or secondary to long-range linkage disequilibrium. The complement C4 locus, located in the major histocompatibility complex (MHC) class III region, exhibits copy-number variation (CNV) and C4 itself exists as two paralogs, C4A and C4B. In order to determine whether partial C4 deficiency is an independent genetic risk factor for SLE, we investigated C4 CNV in the context of HLA-DRB1 and MHC region SNP polymorphism in the largest and most comprehensive complement C4 study to date. Specifically, we genotyped 2,207 subjects of northern and southern European ancestry (1,028 SLE cases and 1,179 controls) for total C4, C4A, and C4B gene copy numbers, and the loss-of-function C4 exon 29 CT indel. We used multiple logistic regression to determine the independence of C4 CNV from known SNP and HLA-DRB1 associations. We clearly demonstrate that genetically determined partial C4 deficiency states are not independent risk factors for SLE in UK and Spanish populations. These results are further corroborated by the lack of association shown by the C4A exon 29 CT insertion in either cohort. Thus, although complete homozygous deficiency of complement C4 is one of the strongest genetic risk factors for SLE, partial C4 deficiency states do not independently predispose to the disease.
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