ArticleAmerican journal of human genetics2007
Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans.
Article in American journal of human genetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 papers, 2 of them syntheses that pooled it.
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Who cites it
232 citing papers in PubMed, 2 syntheses or guidelines pooled it, 465 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Association between complement 4 copy number variation and systemic lupus erythematosus: a meta-analysis.Clinical and experimental medicine · 2020Pooled it
- C4B gene influences intestinal microbiota through complement activation in patients with paediatric-onset inflammatory bowel disease.Clinical and experimental immunology · 2017Trial
- Trial
- From Genes to Pathways: The Molecular Landscape of Systemic Lupus Erythematosus.International journal of molecular sciences · 2026Review
- Distinct Effects of Complement C4A and C4B Copy Numbers in Systemic Sclerosis Serological and Clinical Subtypes.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Integrating genomic structural equation modeling and experimental validation to unravel the genetic basis of male genital lichen sclerosus.Frontiers in immunology · 2026Article
- Copy number variation at the complement C4 locus is associated with risk for multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2025Article
- Post-transplant Thrombotic Microangiopathy.Journal of the American Society of Nephrology : JASN · 2025Review
- Structural polymorphism and diversity of human segmental duplications.Nature genetics · 2025Article
- Copy Number Variation in Asthma: An Integrative Review.Clinical reviews in allergy & immunology · 2025Review
- Monocyte uptake of polymeric peptidoglycan is bimodal and governed by complement C3 and C4 opsonins.JCI insight · 2024Article
- Systemic lupus erythematosus genetics: insights into pathogenesis and implications for therapy.Nature reviews. Rheumatology · 2024Review
- Article
- The rs3918188 and rs1799983 loci of eNOS gene are associated with susceptibility in patients with systemic lupus erythematosus in Northeast China.Scientific reports · 2024Article
- 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
- Structural polymorphism and diversity of human segmental duplications.bioRxiv : the preprint server for biology · 2024Article
- The 330 risk loci known for systemic lupus erythematosus (SLE): a review.Frontiers in lupus · 2024Article
- Uncovering lupus nephritis-specific genes and the potential of TNFRSF17-targeted immunotherapy: a high-throughput sequencing study.Frontiers in immunology · 2024Article
- Genetic interrogation for sequence and copy number variants in systemic lupus erythematosus.Frontiers in genetics · 2024Review
172 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 1 country.
Funding
Abstract
Interindividual gene copy-number variation (CNV) of complement component C4 and its associated polymorphisms in gene size (long and short) and protein isotypes (C4A and C4B) probably lead to different susceptibilities to autoimmune disease. We investigated the C4 gene CNV in 1,241 European Americans, including patients with systemic lupus erythematosus (SLE), their first-degree relatives, and unrelated healthy subjects, by definitive genotyping and phenotyping techniques. The gene copy number (GCN) varied from 2 to 6 for total C4, from 0 to 5 for C4A, and from 0 to 4 for C4B. Four copies of total C4, two copies of C4A, and two copies of C4B were the most common GCN counts, but each constituted only between one-half and three-quarters of the study populations. Long C4 genes were strongly correlated with C4A (R=0.695; P<.0001). Short C4 genes were correlated with C4B (R=0.437; P<.0001). In comparison with healthy subjects, patients with SLE clearly had the GCN of total C4 and C4A shifting to the lower side. The risk of SLE disease susceptibility significantly increased among subjects with only two copies of total C4 (patients 9.3%; unrelated controls 1.5%; odds ratio [OR] = 6.514; P=.00002) but decreased in those with > or =5 copies of C4 (patients 5.79%; controls 12%; OR=0.466; P=.016). Both zero copies (OR=5.267; P=.001) and one copy (OR=1.613; P=.022) of C4A were risk factors for SLE, whereas > or =3 copies of C4A appeared to be protective (OR=0.574; P=.012). Family-based association tests suggested that a specific haplotype with a single short C4B in tight linkage disequilibrium with the -308A allele of TNFA was more likely to be transmitted to patients with SLE. This work demonstrates how gene CNV and its related polymorphisms are associated with the susceptibility to a human complex disease.
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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.