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...
- 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/
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|
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 |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.redcol.spa.fl_str_mv |
https://purl.org/redcol/resource_type/ART |
dc.type.local.spa.fl_str_mv |
Artículo de investigación |
format |
http://purl.org/coar/resource_type/c_2df8fbb1 |
status_str |
publishedVersion |
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/ |
dc.rights.accessrights.spa.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.creativecommons.spa.fl_str_mv |
https://creativecommons.org/licenses/by-nc/4.0/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc/2.5/co/ http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc/4.0/ |
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 |
bitstream.url.fl_str_mv |
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MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio Institucional Universidad de Antioquia |
repository.mail.fl_str_mv |
andres.perez@udea.edu.co |
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1812173252057890816 |
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.coTk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo= |