ArticleAnnals of the rheumatic diseases2016
Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA.
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Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7citing papers in PubMed
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7 citing papers in PubMed, 16 citations in OpenAlex.
- Advances in the lectin pathway in systemic lupus erythematosus: from clinical correlations and mechanisms to targeted interventions.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Recurrent anti-TIF1γ-positive dermatomyositis coexisting with postoperative parotid lymphoepithelial carcinoma: a case report with pathogenesis analysis.Frontiers in immunology · 2026Article
- Regulatory Architecture of the RCA Gene Cluster Captures an Intragenic TAD Boundary, CTCF-Mediated Chromatin Looping and a Long-Range Intergenic Enhancer.Frontiers in immunology · 2022Article
- Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing: A pilot study.World journal of clinical cases · 2020Article
- Modelling clinical systemic lupus erythematosus: similarities, differences and success stories.Rheumatology (Oxford, England) · 2017Review
- Association of Complement Receptor 2 Gene Polymorphisms with Susceptibility to Osteonecrosis of the Femoral Head in Systemic Lupus Erythematosus.BioMed research international · 2016Article
- Advances in lupus genetics.Current opinion in rheumatology · 2015Review
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Authors and funding
49 authors at 20 institutions in 7 countries.
Jian ZhaoDivision of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Brendan M GilesDivision of Rheumatology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Rhonda L TaylorSchool of Pathology and Laboratory Medicine, Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, Western Australia, Australia.
Gabriel A YetteDivision of Rheumatology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Kara M LoughDivision of Rheumatology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Han Leng NgSchool of Pathology and Laboratory Medicine, Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, Western Australia, Australia.
Lawrence J AbrahamSchool of Pathology and Laboratory Medicine, Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, Western Australia, Australia.
Hui WuDivision of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Jennifer A KellyArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Stuart B GlennArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Adam J AdlerArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Adrienne H WilliamsDepartment of Biostatistical Sciences and Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Mary E ComeauDepartment of Biostatistical Sciences and Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Julie T ZieglerDepartment of Biostatistical Sciences and Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Miranda MarionDepartment of Biostatistical Sciences and Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Marta E Alarcón-RiquelmeArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Pfizer-Universidad de Granada-Junta de Andalucía Center for Genomics and Oncological Research, Granada, Spain.
BIOLUPUS and GENLES Networks
Graciela S AlarcónDepartment of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Juan-Manuel AnayaCenter for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, Colombia.
Sang-Cheol BaeDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
Dam KimDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
Hye-Soon LeeDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
Lindsey A CriswellRosalind Russell/Ephraim P. Engleman Rheumatology Research Center, University of California San Francisco, San Francisco, California, USA.
Barry I FreedmanDepartment of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Gary S GilkesonDivision of Rheumatology, Medical University of South Carolina, Charleston, South Carolina, USA.
Joel M GuthridgeArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Chaim O JacobDepartment of Medicine, University of Southern California, Los Angeles, California, USA.
Judith A JamesArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Diane L KamenDivision of Rheumatology, Medical University of South Carolina, Charleston, South Carolina, USA.
Joan T MerrillDepartment of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Kathy Moser SivilsArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Timothy B NiewoldDivision of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
Michelle A PetriDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Rosalind Ramsey-GoldmanDivision of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
John D ReveilleDepartment of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas, USA.
R Hal ScofieldArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA US Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA.
Anne M StevensDivision of Rheumatology, Department of Pediatrics, University of Washington, Seattle, Washington, USA Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA.
Luis M ViláDivision of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
Timothy J VyseDivision of Genetics and Molecular Medicine and Immunology, King's College London, London, UK.
Kenneth M KaufmanCincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA.
John B HarleyCincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA.
Carl D LangefeldDepartment of Biostatistical Sciences and Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Patrick M GaffneyArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Elizabeth E BrownDepartment of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Jeffrey C EdbergDepartment of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Robert P KimberlyDepartment of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Daniela UlgiatiSchool of Pathology and Laboratory Medicine, Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, Western Australia, Australia.
Betty P TsaoDivision of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Susan A BoackleDivision of Rheumatology, University of Colorado School of Medicine, Aurora, Colorado, USA Denver Veterans Affairs Medical Center, Denver, Colorado, USA.
Oklahoma Medical Research Foundation · USNorth Carolina Division of Public Health · USThe University of Western Australia · AUUniversity of Alabama at Birmingham · USUniversity of Colorado Denver · USHanyang University Seoul Hospital · KRUniversity of California, Los Angeles · USMedical University of South Carolina · USJohns Hopkins Medicine · USKing's College London · GBNorthwestern University · USSeattle Children's Hospital · USThe University of Texas Health Science Center at Houston · USUnited States Department of Veterans Affairs · USUniversidad del Rosario · COUniversity of California, San Francisco · USUniversity of Puerto Rico, Medical Sciences Campus · PRUniversity of Southern California · USVeterans Health Administration · USWake Forest University · US
Funding
University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0MTransform Dissemination and Implementation Science in CTSA ProgramsUL1TR002319 · NCATS · UNIVERSITY OF WASHINGTON · PI John K. Amory · 2017 to 2026
$100.0MEngaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0MTracking and Evaluation CoreU54GM104938 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI PAUL G SPICER · 2013 to 2026
$68.2MNorthwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8MINSTITUTE FOR TRANSLATIONAL HEALTH SCIENCE (UL1): BPCAUL1RR025014 · NCRR · UNIVERSITY OF WASHINGTON · PI DISIS, MARY L. · 2007 to 2011
$51.5MColorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0MLCenter for Clinical and Translational Science and TrainingUL1TR001425 · NCATS · UNIVERSITY OF CINCINNATI · PI MEINZEN-DERR, JAREEN, STRAWN, JEFFREY ROBERT · 2015 to 2024
$37.5MUAB Center for Clinical and Translational Science (CCTS)UL1TR001417 · NCATS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KIMBERLY, ROBERT P. · 2015 to 2018
$31.4MTRANSLATIONAL RESEARCH UNIVERSITY OF CHICAGO: CLINICAL TRIALSUL1RR024999 · NCRR · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2007 to 2011
$25.3MMULTIDISCIPLINARY CLINICAL AND TRANSLATIONAL SCIENCE (MCTS) PROGRAM (UL1)UL1RR025741 · NCRR · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GREENLAND, PHILIP · 2008 to 2011
$24.7MUAB CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE (CCTS) UL1: BPCAUL1RR025777 · NCRR · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GUAY-WOODFORD, LISA MARIE · 2008 to 2011
$22.3MBLRD VA I01 BX001834NCATS NIH HHS UL1 TR000004NCATS NIH HHS UL1TR000004NCATS NIH HHS UL1 TR000154NCATS NIH HHS UL1 TR000371NCATS NIH HHS UL1 TR000430NCATS NIH HHS UL1 TR001082NCATS NIH HHS UL1 TR001417NCATS NIH HHS UL1 TR001422NCATS NIH HHS UL1 TR001425NCATS NIH HHS UL1 TR002319NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA141700NCI NIH HHS R01CA141700NCRR NIH HHS P20 RR020143NCRR NIH HHS P20RR020143NCRR NIH HHS U54RR023417NCRR NIH HHS UL1 RR024999NCRR NIH HHS UL1RR024999NCRR NIH HHS UL1 RR025014NCRR NIH HHS UL1RR025014NCRR NIH HHS UL1 RR025741NCRR NIH HHS UL1RR025741NCRR NIH HHS UL1 RR025777NCRR NIH HHS UL1RR025777NCRR NIH HHS UL1 RR029882NCRR NIH HHS UL1RR029882NIAID NIH HHS K08 AI083790NIAID NIH HHS K08AI083790NIAID NIH HHS K24 AI078004NIAID NIH HHS K24AI078004NIAID NIH HHS P01 AI083194NIAID NIH HHS P01AI083194NIAID NIH HHS R01 AI063274NIAID NIH HHS R01AI063274NIAID NIH HHS R01 AI070983NIAID NIH HHS R01AI070983NIAID NIH HHS R21 AI070304NIAID NIH HHS R21AI070304NIAID NIH HHS R37 AI024717NIAID NIH HHS R37AI024717NIAID NIH HHS U01 AI101934NIAID NIH HHS U01AI101934NIAID NIH HHS U19 AI082714NIAID NIH HHS U19AI082714NIAMS NIH HHS K24 AR002138NIAMS NIH HHS K24AR002138NIAMS NIH HHS N01 AR062277NIAMS NIH HHS P01 AR049084NIAMS NIH HHS P01AR049084NIAMS NIH HHS P30 AR048311NIAMS NIH HHS P30AR048311NIAMS NIH HHS P30 AR053483NIAMS NIH HHS P30AR053483NIAMS NIH HHS P30AR055385NIAMS NIH HHS P60 AR030692NIAMS NIH HHS P60 AR053308NIAMS NIH HHS P60AR053308NIAMS NIH HHS P60 AR062755NIAMS NIH HHS P60AR062755NIAMS NIH HHS R01 AR033062NIAMS NIH HHS R01AR033062NIAMS NIH HHS R01 AR042460NIAMS NIH HHS R01AR042460NIAMS NIH HHS R01 AR043274NIAMS NIH HHS R01AR043274NIAMS NIH HHS R01 AR043727NIAMS NIH HHS R01 AR043814NIAMS NIH HHS R01AR043814NIAMS NIH HHS R01 AR051545NIAMS NIH HHS R01AR051545NIAMS NIH HHS R01 AR057172NIAMS NIH HHS R01AR057172NIAMS NIH HHS R01 AR064820NIAMS NIH HHS R01AR43727NIAMS NIH HHS RC1 AR058621NIAMS NIH HHS RC1AR058621NIAMS NIH HHS T32 AR007534NIAMS NIH HHS T32AR07534NIDDK NIH HHS P30 DK057516NIDDK NIH HHS P30 DK57516NIGMS NIH HHS P30 GM103510NIGMS NIH HHS P30GM103510NIGMS NIH HHS U54 GM104938PHS HHS LRPAI071651Wellcome Trust
Abstract
objectivesSystemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association.
methodsGenotyped and imputed genetic variants spanning CR2 were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR.
resultsThe strongest association signal was detected at rs1876453 in intron 1 of CR2 (pmeta=4.2×10(-4), OR 0.85), specifically when subjects were stratified based on the presence of dsDNA autoantibodies (case-control pmeta=7.6×10(-7), OR 0.71; case-only pmeta=1.9×10(-4), OR 0.75). Although allele-specific effects on B cell CR2 mRNA or protein levels were not identified, levels of complement receptor 1 (CR1/CD35) mRNA and protein were significantly higher on B cells of subjects harbouring the minor allele (p=0.0248 and p=0.0006, respectively). The minor allele altered the formation of several DNA protein complexes by EMSA, including one containing CCCTC-binding factor (CTCF), an effect that was confirmed by ChIP-PCR.
conclusionsThese data suggest that rs1876453 in CR2 has long-range effects on gene regulation that decrease susceptibility to lupus. Since the minor allele at rs1876453 is preferentially associated with reduced risk of the highly specific dsDNA autoantibodies that are present in preclinical, active and severe lupus, understanding its mechanisms will have important therapeutic implications.
Indexed as
AdolescentAdultAntibodies, AntinuclearB-Lymphocyte SubsetsCase-Control StudiesDNAGenetic Predisposition to DiseaseGenetic VariationGenotypeHaplotypesHumansLupus Erythematosus, SystemicMiddle AgedPhenotypePolymorphism, Single NucleotideReceptors, Complement 3bAntibodies, AntinuclearCR1 protein, humanDNAReceptors, Complement 3bReceptors, Complement 3dTranscription FactorsAutoantibodiesB cellsGene PolymorphismSystemic Lupus Erythematosus
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