Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility
Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associa...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2011
- Institución:
- Universidad del Rosario
- Repositorio:
- Repositorio EdocUR - U. Rosario
- Idioma:
- eng
- OAI Identifier:
- oai:repository.urosario.edu.co:10336/8779
- Acceso en línea:
- https://doi.org/10.1371/journal.pgen.1002079
http://repository.urosario.edu.co/handle/10336/8779
- Palabra clave:
- Enfermedades
Genes
Genética
Lupus eritematoso sistémico
Inmunología
Complement factor H
Complement regulator factor H related protein 1
Complement regulator factor H related protein 2
Complement regulator factor H related protein
Plasma protein
Unclassified drug
Bladder tumor associated antigen
Complement factor H
Tumor antigen
Tumor marker
- Rights
- License
- Abierto (Texto completo)
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dc.title.spa.fl_str_mv |
Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility |
title |
Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility |
spellingShingle |
Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility Enfermedades Genes Genética Lupus eritematoso sistémico Inmunología Complement factor H Complement regulator factor H related protein 1 Complement regulator factor H related protein 2 Complement regulator factor H related protein Plasma protein Unclassified drug Bladder tumor associated antigen Complement factor H Tumor antigen Tumor marker |
title_short |
Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility |
title_full |
Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility |
title_fullStr |
Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility |
title_full_unstemmed |
Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility |
title_sort |
Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility |
dc.creator.google.none.fl_str_mv |
Lee, Eun Young Boackle, Susan A. Grossman, Jennifer M. Hahn, Bevra H. Goodship, Timothy H. J. Cantor, Rita M. Yu, Chack-Yung Shen, Nan Tsao, Betty P. |
dc.subject.ddc.none.fl_str_mv |
Enfermedades |
topic |
Enfermedades Genes Genética Lupus eritematoso sistémico Inmunología Complement factor H Complement regulator factor H related protein 1 Complement regulator factor H related protein 2 Complement regulator factor H related protein Plasma protein Unclassified drug Bladder tumor associated antigen Complement factor H Tumor antigen Tumor marker |
dc.subject.decs.spa.fl_str_mv |
Genes Genética Lupus eritematoso sistémico Inmunología |
dc.subject.keyword.eng.fl_str_mv |
Complement factor H Complement regulator factor H related protein 1 Complement regulator factor H related protein 2 Complement regulator factor H related protein Plasma protein Unclassified drug Bladder tumor associated antigen Complement factor H Tumor antigen Tumor marker |
description |
Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE. |
publishDate |
2011 |
dc.date.created.none.fl_str_mv |
2011-05-26 |
dc.date.issued.none.fl_str_mv |
2011 |
dc.date.accessioned.none.fl_str_mv |
2014-08-11T20:52:03Z |
dc.date.available.none.fl_str_mv |
2014-08-11T20:52:03Z |
dc.type.eng.fl_str_mv |
article |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.spa.spa.fl_str_mv |
Artículo |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1371/journal.pgen.1002079 |
dc.identifier.issn.none.fl_str_mv |
1553-7390 |
dc.identifier.uri.none.fl_str_mv |
http://repository.urosario.edu.co/handle/10336/8779 |
url |
https://doi.org/10.1371/journal.pgen.1002079 http://repository.urosario.edu.co/handle/10336/8779 |
identifier_str_mv |
1553-7390 |
dc.language.iso.none.fl_str_mv |
eng |
language |
eng |
dc.relation.citationIssue.none.fl_str_mv |
No. 5 |
dc.relation.citationTitle.none.fl_str_mv |
PLoS Genetics |
dc.relation.citationVolume.none.fl_str_mv |
Vol. 7 |
dc.relation.ispartof.spa.fl_str_mv |
PLoS Genetics ISSN 15537390 V. 7 N. 5 May 2011 |
dc.relation.uri.none.fl_str_mv |
http://www.plosgenetics.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pgen.1002079&representation=PDF |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.acceso.spa.fl_str_mv |
Abierto (Texto completo) |
rights_invalid_str_mv |
Abierto (Texto completo) http://purl.org/coar/access_right/c_abf2 |
dc.format.medium.spa.fl_str_mv |
Recurso electrónico |
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application/pdf |
dc.format.tipo.spa.fl_str_mv |
Documento |
dc.publisher.spa.fl_str_mv |
Universidad del Rosario |
institution |
Universidad del Rosario |
dc.source.instname.spa.fl_str_mv |
instname:Universidad del Rosario |
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reponame:Repositorio Institucional EdocUR |
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Comunidad Rosarista1285b2a5-e260-4c3f-8808-4a5533e566aa600446a6c8a-23e0-4740-b64c-a3064b390fd66001fd4dfcb-0903-411e-8182-ac5636612671600c2744fc5-d1ea-4406-8647-51884310c9db600d90ea1fb-511c-4f43-8ae6-97078c334f756006eceab3a-7c5d-4670-a9a8-60ea0c978b0360006d736b0-74df-4660-b37e-3a005f8732a56001346a4e8-7d7b-4747-85ac-4046be1997f76000a90518b-9a6a-4630-bdd7-92469604cd036000174e7f3-b46d-453e-94fb-1b1670c7be0b6008b80c26e-41b7-44e2-849f-3f23495ab9786005ed984fc-7c9d-4095-a1b3-2f6ad4d711e3600a2cb39c5-5419-4d07-b688-5d6c67c230f4600e4c3809e-f0e3-4273-9f2e-21418f35d5d3600ee2b0a18-7380-46ca-8efb-e4f1faeaaa5260028a11ecc-4e3c-440e-bc2c-07c632e8a4c96007db99122-14fd-4cf7-8433-c6ea25aac9536007d14c4ec-5de6-4708-b541-999d5914baac600c11a167e-f3af-4598-a4cc-12063a62f413600e528f176-564e-4bbc-9ca8-02c74a42f07c60019fa32b9-3bc1-446c-a582-50f1e4bf7acb600aa79f5ef-3d3d-434b-9953-b294f92dcb536006bd1fd7e-8035-4f70-b798-2b76ea3b1307600745e1f5a-a9e9-4bc2-b74c-b681dc65c7586003568b65a-bc38-49f5-b7fa-4291ae155adb600c4bfdc11-7dbd-4d4e-b73c-9064278d4f2760031bbf3ec-053f-4cc0-b64b-2673b41360f4600406e0c2e-fd73-4611-8e1f-2a0bc491d782600e0b9385e-e27f-4690-9682-38534cadc6a360038835a7b-4cbd-4b5c-a2a3-73d2c30770c460071e4fbaf-406c-4c59-8872-0bb828452e5e6007d03cd58-5bb1-4a37-8ea5-a65b0942f83f60010d0b1ab-4cac-49e6-8e57-58de54ba046f6008413200a-d245-4a47-9bf8-a656d5ac34ae6004ada1fd9-edf1-431a-a7b3-3edf2a1c827b60014cc1f32-efb9-4a86-bab9-8030168be37b600d6e1abf0-ce1e-497f-b3ba-a62ff14398d660019474778600ef52afb8-0580-4dde-bb9c-53dbf521427b600cdb7ac73-e49d-4e57-b50f-a2a102dd9ff96001deaa8bc-795f-4973-8456-d0f36a56f0b5600b66a6bb0-2fde-45fa-91d6-6e81769d7bea60034b38e53-a3b1-4101-a8df-21cac0cb931660046cf427c-ec81-4a13-bb17-6755400ac55a60000bb664f-a9ec-477e-a844-40749a95038f60002c2ea22-e5fe-4fb4-94cc-12efe968ace2600f79c88f7-a304-4bca-822d-b1af01871b256006b06681e-0b8a-4d48-9ba0-c472b99139d6600f3e49ab2-cdb6-4740-8141-0a0dd4ccea75600b3e386c2-6be4-4964-91cc-d3c5f5791068600dbb43164-24dc-4558-aefa-aed76ea13c6a600f6dcee8e-d5a5-452a-85d1-697bd44668cc600620935a5-8b1c-4f10-92cb-323b2fc9d0a16009f7f48b7-804c-4a28-aa04-943135e42ffe60045ab12f3-bc9b-4eba-a1ff-0380573125f8600Lee, Eun YoungBoackle, Susan A.Grossman, Jennifer M.Hahn, Bevra H.Goodship, Timothy H. J.Cantor, Rita M.Yu, Chack-YungShen, NanTsao, Betty P.2014-08-11T20:52:03Z2014-08-11T20:52:03Z2011-05-262011Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the CFH-CFHRs region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic CFH SNP (rs6677604, in intron 11, Pmeta = 6.6×10-8, OR = 1.18) and an intergenic SNP between CFHR1 and CFHR4 (rs16840639, Pmeta = 2.9×10-7, OR = 1.17) rather than to previously identified disease-associated CFH exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ~146 kb block extending from intron 9 of CFH to downstream of CFHR1. Within this block, the deletion of CFHR3 and CFHR1 (CFHR3-1Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of CFHR3-1Δ (Pmeta = 3.2×10-7, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (Pmeta = 3.5×10-4, OR = 1.14). These results suggested that the CFHR3-1Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of CFH, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.Recurso electrónicoapplication/pdfDocumentohttps://doi.org/10.1371/journal.pgen.10020791553-7390http://repository.urosario.edu.co/handle/10336/8779engUniversidad del RosarioNo. 5PLoS GeneticsVol. 7PLoS Genetics ISSN 15537390 V. 7 N. 5 May 2011http://www.plosgenetics.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pgen.1002079&representation=PDFAbierto (Texto completo)EL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma.http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocUREnfermedades616600GenesGenéticaLupus eritematoso sistémicoInmunologíaComplement factor HComplement regulator factor H related protein 1Complement regulator factor H related protein 2Complement regulator factor H related proteinPlasma proteinUnclassified drugBladder tumor associated antigenComplement factor HTumor antigenTumor markerAssociation of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibilityarticleArtículohttp://purl.org/coar/resource_type/c_6501Zhao, JianWu, HuiKhosravi, MelanieCui, HuijuanQian, XiaoxiaKelly, Jennifer A.Kaufman, Kenneth M.Langefeld, Carl D.Williams, Adrienne H.Comeau, MaryZiegler, Julie T.Marion, Miranda C.Adler, AdamGlenn, Stuart B.Alarcón-Riquelme, Marta E.Pons-Estel, Bernardo A.Harley, John B.Bae, Sang-CheolBang, So-YoungCho, Soo-KyungJacob, Chaim O.Vyse, Timothy J.Niewold, Timothy B.Gaffney, Patrick M.Moser, Kathy L.Kimberly, Robert P.Edberg, Jeffrey C.Brown, Elizabeth E.Alarcón, Graciela S.Petri, Michelle A.Ramsey-Goldman, RosalindVilá, Luis M.Reveille, John D.James, Judith A.Gilkeson, Gary S.Kamen, Diane L.Freedman, Barry I.Anaya, Juan-ManuelMerrill, Joan T.Criswell, Lindsey A.Scofield, Robert H.Stevens, Anne M.Guthridge, Joel M.Chang, Deh-MingSong, Yeong WookPark, Ji AhYoung Lee, EunBoackle, SusanGrossman, Jennifer M.Hahn, Bevra H.Goodship, Timothy H. J.Cantor, Rita M.Yu, Chack-YungShen, NanTsao, Betty P.Zhao, JianWu, HuiKhosravi, MelanieCui, HuijuanQian, XiaoxiaKelly, Jennifer A.Kaufman, Kenneth M.Langefeld, Carl D.Williams, Adrienne H.Comeau, Mary E.Ziegler, Julie T.Marion, Miranda C.Adler, AdamGlenn, Stuart B.Alarcón-Riquelme, Marta E.Pons-Estel, Bernardo A.Harley, John B.Bae, Sang-CheolBang, So-YoungCho, Soo-KyungJacob, Chaim O.Vyse, Timothy J.Niewold, Timothy B.Gaffney, Patrick M.Moser, Kathy L.Kimberly, Robert P.Edberg, Jeffrey C.Brown, Elizabeth E.Alarcon, Graciela S.Petri, Michelle A.Ramsey-Goldman, RosalindVilá, Luis M.Reveille, John D.James, Judith A.Gilkeson, Gary S.Kamen, Diane L.Freedman, Barry I.Anaya, Juan-ManuelMerrill, Joan T.Criswell, Lindsey A.Scofield, R. HalStevens, Anne M.Guthridge, Joel M.Chang, Deh-MingSong, Yeong WookPark, Ji AhORIGINALAssociation of Genetic.pdfAssociation of Genetic.pdfapplication/pdf743916https://repository.urosario.edu.co/bitstreams/4521e1d2-c914-4b8a-82d5-3696e8ce7b9d/downloadd516b1d1040491e188cfee36ef01b617MD51LICENSElicense.txtlicense.txttext/plain2156https://repository.urosario.edu.co/bitstreams/786d8240-ca34-420f-9117-90b3f7e7ab6a/downloadb4f8fe66e94b897ab4c355bac005ad16MD52TEXTAssociation of Genetic.pdf.txtAssociation of Genetic.pdf.txtExtracted texttext/plain55889https://repository.urosario.edu.co/bitstreams/74382248-75dd-434c-81aa-a972dff0d7b7/download85f73a46efd0ab0965fe3a69b17ff1f1MD59THUMBNAILAssociation of Genetic.pdf.jpgAssociation of Genetic.pdf.jpgGenerated Thumbnailimage/jpeg4258https://repository.urosario.edu.co/bitstreams/b7cd08db-00e6-45cd-bbdc-e03683bc85b1/download08d24174b47ae8d4b1844711f0dd5addMD51010336/8779oai:repository.urosario.edu.co:10336/87792022-08-31 10:09:00.969https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.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 |