CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus

ABSTRACT: Objectives There is an enrichment of immune response genes that are subject to copy number variations (CNVs). However, there is limited understanding of their impact on susceptibility to human diseases. CC chemokine ligand 3 like-1 (CCL3L1) is a potent ligand for the HIV coreceptor, CC che...

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Autores:
Mamtani, M.
Rovin, B.
Brey, R.
Camargo, José Fernando
Kulkarni, H.
Herrera, Monica
Correa Vanegas, Paula Andrea
Holliday, S.
Anaya Cabrera, Juan Manuel
Ahuja, S. K.
Tipo de recurso:
Article of investigation
Fecha de publicación:
2008
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/25937
Acceso en línea:
http://hdl.handle.net/10495/25937
Palabra clave:
Lupus Eritematoso Sistémico
Lupus Erythematosus, Systemic
Genes
Quimiocinas
Chemokines
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc/2.5/co/
id UDEA2_e64ad11c6063018ea6ce8ff213b54e65
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/25937
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus
title CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus
spellingShingle CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus
Lupus Eritematoso Sistémico
Lupus Erythematosus, Systemic
Genes
Quimiocinas
Chemokines
title_short CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus
title_full CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus
title_fullStr CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus
title_full_unstemmed CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus
title_sort CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus
dc.creator.fl_str_mv Mamtani, M.
Rovin, B.
Brey, R.
Camargo, José Fernando
Kulkarni, H.
Herrera, Monica
Correa Vanegas, Paula Andrea
Holliday, S.
Anaya Cabrera, Juan Manuel
Ahuja, S. K.
dc.contributor.author.none.fl_str_mv Mamtani, M.
Rovin, B.
Brey, R.
Camargo, José Fernando
Kulkarni, H.
Herrera, Monica
Correa Vanegas, Paula Andrea
Holliday, S.
Anaya Cabrera, Juan Manuel
Ahuja, S. K.
dc.subject.decs.none.fl_str_mv Lupus Eritematoso Sistémico
Lupus Erythematosus, Systemic
Genes
Quimiocinas
Chemokines
topic Lupus Eritematoso Sistémico
Lupus Erythematosus, Systemic
Genes
Quimiocinas
Chemokines
description ABSTRACT: Objectives There is an enrichment of immune response genes that are subject to copy number variations (CNVs). However, there is limited understanding of their impact on susceptibility to human diseases. CC chemokine ligand 3 like-1 (CCL3L1) is a potent ligand for the HIV coreceptor, CC chemokine receptor 5 (CCR5), and we have demonstrated previously an association between CCL3L1- gene containing segmental duplications and polymorphisms in CCR5 and HIV/AIDS susceptibility. Here, we determined the association between these genetic variations and risk of developing systemic lupus erythaematosus (SLE), differential recruitment of CD3+ and CD68+ leukocytes to the kidney, clinical severity of SLE reflected by autoantibody titres and the risk of renal complications in SLE. Methods We genotyped 1084 subjects (469 cases of SLE and 615 matched controls with no autoimmune disease) from three geographically distinct cohorts for variations in CCL3L1 and CCR5. Results Deviation from the average copy number of CCL3L1 found in European populations increased the risk of SLE and modified the SLE-influencing effects of CCR5 haplotypes. The CCR5 human haplogroup (HH)E and CCR5-Δ32-bearing HHG*2 haplotypes were associated with an increased risk of developing SLE. An individual’s CCL3L1–CCR5 genotype strongly predicted the overall risk of SLE, high autoantibody titres, and lupus nephritis as well as the differential recruitment of leukocytes in subjects with lupus nephritis. The CCR5 HHE/HHG*2 genotype was associated with the maximal risk of developing SLE. Conclusion CCR5 haplotypes HHE and HHG*2 strongly influence the risk of SLE. The copy number of CCL3L1 influences risk of SLE and modifies the SLE-influencing effects associated with CCR5 genotypes. These findings implicate a key role of the CCL3L1–CCR5 axis in the pathogenesis of SLE.
publishDate 2008
dc.date.issued.none.fl_str_mv 2008
dc.date.accessioned.none.fl_str_mv 2022-02-09T21:26:45Z
dc.date.available.none.fl_str_mv 2022-02-09T21:26:45Z
dc.type.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.hasversion.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/ART
dc.type.local.spa.fl_str_mv Artículo de investigación
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dc.identifier.citation.spa.fl_str_mv Mamtani, M., Rovin, B., Brey, R., Camargo, J. F., Kulkarni, H., Herrera, M., Correa, P., Holliday, S., Anaya, J. M., & Ahuja, S. K. (2008). CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus. Annals of the rheumatic diseases, 67(8), 1076–1083. https://doi.org/10.1136/ard.2007.078048
dc.identifier.issn.none.fl_str_mv 0003-4967
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/10495/25937
dc.identifier.doi.none.fl_str_mv 10.1136/ard.2007.078048
dc.identifier.eissn.none.fl_str_mv 1468-2060
identifier_str_mv Mamtani, M., Rovin, B., Brey, R., Camargo, J. F., Kulkarni, H., Herrera, M., Correa, P., Holliday, S., Anaya, J. M., & Ahuja, S. K. (2008). CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus. Annals of the rheumatic diseases, 67(8), 1076–1083. https://doi.org/10.1136/ard.2007.078048
0003-4967
10.1136/ard.2007.078048
1468-2060
url http://hdl.handle.net/10495/25937
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Ann. Rheum. Dis.
dc.rights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc/2.5/co/
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eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/2.5/co/
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dc.format.extent.spa.fl_str_mv 7
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv BMJ Publishing Group
dc.publisher.group.spa.fl_str_mv Biología Celular y Molecular CIB U. de A. U. del Rosario
dc.publisher.place.spa.fl_str_mv Londres, Inglaterra
institution Universidad de Antioquia
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spelling Mamtani, M.Rovin, B.Brey, R.Camargo, José FernandoKulkarni, H.Herrera, MonicaCorrea Vanegas, Paula AndreaHolliday, S.Anaya Cabrera, Juan ManuelAhuja, S. K.2022-02-09T21:26:45Z2022-02-09T21:26:45Z2008Mamtani, M., Rovin, B., Brey, R., Camargo, J. F., Kulkarni, H., Herrera, M., Correa, P., Holliday, S., Anaya, J. M., & Ahuja, S. K. (2008). CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus. Annals of the rheumatic diseases, 67(8), 1076–1083. https://doi.org/10.1136/ard.2007.0780480003-4967http://hdl.handle.net/10495/2593710.1136/ard.2007.0780481468-2060ABSTRACT: Objectives There is an enrichment of immune response genes that are subject to copy number variations (CNVs). However, there is limited understanding of their impact on susceptibility to human diseases. CC chemokine ligand 3 like-1 (CCL3L1) is a potent ligand for the HIV coreceptor, CC chemokine receptor 5 (CCR5), and we have demonstrated previously an association between CCL3L1- gene containing segmental duplications and polymorphisms in CCR5 and HIV/AIDS susceptibility. Here, we determined the association between these genetic variations and risk of developing systemic lupus erythaematosus (SLE), differential recruitment of CD3+ and CD68+ leukocytes to the kidney, clinical severity of SLE reflected by autoantibody titres and the risk of renal complications in SLE. Methods We genotyped 1084 subjects (469 cases of SLE and 615 matched controls with no autoimmune disease) from three geographically distinct cohorts for variations in CCL3L1 and CCR5. Results Deviation from the average copy number of CCL3L1 found in European populations increased the risk of SLE and modified the SLE-influencing effects of CCR5 haplotypes. The CCR5 human haplogroup (HH)E and CCR5-Δ32-bearing HHG*2 haplotypes were associated with an increased risk of developing SLE. An individual’s CCL3L1–CCR5 genotype strongly predicted the overall risk of SLE, high autoantibody titres, and lupus nephritis as well as the differential recruitment of leukocytes in subjects with lupus nephritis. The CCR5 HHE/HHG*2 genotype was associated with the maximal risk of developing SLE. Conclusion CCR5 haplotypes HHE and HHG*2 strongly influence the risk of SLE. The copy number of CCL3L1 influences risk of SLE and modifies the SLE-influencing effects associated with CCR5 genotypes. These findings implicate a key role of the CCL3L1–CCR5 axis in the pathogenesis of SLE.COL00009627application/pdfengBMJ Publishing GroupBiología Celular y Molecular CIB U. de A. U. del RosarioLondres, Inglaterrainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc/2.5/co/http://purl.org/coar/access_right/c_abf2https://creativecommons.org/licenses/by-nc/4.0/CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosusLupus Eritematoso SistémicoLupus Erythematosus, SystemicGenesQuimiocinasChemokinesAnn. Rheum. Dis.Annals of the Rheumatic Diseases10761083678ORIGINALMamtaniM_2008_.pdfMamtaniM_2008_.pdfArtículo de investigaciónapplication/pdf1399536https://bibliotecadigital.udea.edu.co/bitstream/10495/25937/1/MamtaniM_2008_.pdf268f172a02d3000e4b9c9c82fcf2ba51MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8933https://bibliotecadigital.udea.edu.co/bitstream/10495/25937/2/license_rdfc0c92b0ffc8b7d22d9cf56754a416a76MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstream/10495/25937/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD5310495/25937oai:bibliotecadigital.udea.edu.co:10495/259372022-11-13 18:40:22.414Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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