Evaluation of TRAF6 in a large multiancestral lupus cohort

Objective Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role i...

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Fecha de publicación:
2012
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/22999
Acceso en línea:
https://doi.org/10.1002/art.34361
https://repository.urosario.edu.co/handle/10336/22999
Palabra clave:
Tumor necrosis factor receptor associated factor 6
African american
Article
Calculation
Controlled study
Ethnicity
Female
Gene linkage disequilibrium
Genetic association
Genetic heterogeneity
Genotype
Heredity
Human
Immunity
Immunopathogenesis
Major clinical study
Male
Meta analysis (topic)
Organogenesis
Pedigree analysis
Population based case control study
Priority journal
Rheumatoid arthritis
Signal transduction
Single nucleotide polymorphism
Systemic lupus erythematosus
Thrombocytopenia
Alleles
Case-control studies
Cohort studies
Female
Gene frequency
Genetic association studies
Genetic predisposition to disease
Genotype
Haplotypes
Humans
Male
Tnf receptor-associated factor 6
systemic
single nucleotide
Lupus erythematosus
Polymorphism
Rights
License
Abierto (Texto Completo)
id EDOCUR2_35ccbe443cff5cf096375bedccd37b01
oai_identifier_str oai:repository.urosario.edu.co:10336/22999
network_acronym_str EDOCUR2
network_name_str Repositorio EdocUR - U. Rosario
repository_id_str
dc.title.spa.fl_str_mv Evaluation of TRAF6 in a large multiancestral lupus cohort
title Evaluation of TRAF6 in a large multiancestral lupus cohort
spellingShingle Evaluation of TRAF6 in a large multiancestral lupus cohort
Tumor necrosis factor receptor associated factor 6
African american
Article
Calculation
Controlled study
Ethnicity
Female
Gene linkage disequilibrium
Genetic association
Genetic heterogeneity
Genotype
Heredity
Human
Immunity
Immunopathogenesis
Major clinical study
Male
Meta analysis (topic)
Organogenesis
Pedigree analysis
Population based case control study
Priority journal
Rheumatoid arthritis
Signal transduction
Single nucleotide polymorphism
Systemic lupus erythematosus
Thrombocytopenia
Alleles
Case-control studies
Cohort studies
Female
Gene frequency
Genetic association studies
Genetic predisposition to disease
Genotype
Haplotypes
Humans
Male
Tnf receptor-associated factor 6
systemic
single nucleotide
Lupus erythematosus
Polymorphism
title_short Evaluation of TRAF6 in a large multiancestral lupus cohort
title_full Evaluation of TRAF6 in a large multiancestral lupus cohort
title_fullStr Evaluation of TRAF6 in a large multiancestral lupus cohort
title_full_unstemmed Evaluation of TRAF6 in a large multiancestral lupus cohort
title_sort Evaluation of TRAF6 in a large multiancestral lupus cohort
dc.subject.keyword.spa.fl_str_mv Tumor necrosis factor receptor associated factor 6
African american
Article
Calculation
Controlled study
Ethnicity
Female
Gene linkage disequilibrium
Genetic association
Genetic heterogeneity
Genotype
Heredity
Human
Immunity
Immunopathogenesis
Major clinical study
Male
Meta analysis (topic)
Organogenesis
Pedigree analysis
Population based case control study
Priority journal
Rheumatoid arthritis
Signal transduction
Single nucleotide polymorphism
Systemic lupus erythematosus
Thrombocytopenia
Alleles
Case-control studies
Cohort studies
Female
Gene frequency
Genetic association studies
Genetic predisposition to disease
Genotype
Haplotypes
Humans
Male
Tnf receptor-associated factor 6
topic Tumor necrosis factor receptor associated factor 6
African american
Article
Calculation
Controlled study
Ethnicity
Female
Gene linkage disequilibrium
Genetic association
Genetic heterogeneity
Genotype
Heredity
Human
Immunity
Immunopathogenesis
Major clinical study
Male
Meta analysis (topic)
Organogenesis
Pedigree analysis
Population based case control study
Priority journal
Rheumatoid arthritis
Signal transduction
Single nucleotide polymorphism
Systemic lupus erythematosus
Thrombocytopenia
Alleles
Case-control studies
Cohort studies
Female
Gene frequency
Genetic association studies
Genetic predisposition to disease
Genotype
Haplotypes
Humans
Male
Tnf receptor-associated factor 6
systemic
single nucleotide
Lupus erythematosus
Polymorphism
dc.subject.keyword.eng.fl_str_mv systemic
single nucleotide
Lupus erythematosus
Polymorphism
description Objective Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development. Methods Fifteen single-nucleotide polymorphisms (SNPs) across TRAF6 were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population-based case-control association analyses and meta-analyses were performed. P values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results Evidence of associations was detected in multiple SNPs. The best overall P values were obtained for SNPs rs5030437 and rs4755453 (P = 7.85 × 10 -5 and P = 4.73 × 10 -5, respectively) without significant heterogeneity among populations (P = 0.67 and P = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r 2 = 0.95) and demonstrated evidence of association with SLE in the same direction (meta-analysis P = 9.15 × 10 -4, OR 0.89 [95% CI 0.83-0.95]). The presence of thrombocytopenia improved the overall results in different populations (meta-analysis P = 1.99 × 10 -6, OR 0.57 [95% CI 0.45-0.72], for rs5030470). Finally, evidence of family-based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (P = 0.02) under a dominant model. Conclusion Our data indicate the presence of association of TRAF6 with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity. Copyright © 2012 by the American College of Rheumatology.
publishDate 2012
dc.date.created.spa.fl_str_mv 2012
dc.date.accessioned.none.fl_str_mv 2020-05-25T23:59:11Z
dc.date.available.none.fl_str_mv 2020-05-25T23:59:11Z
dc.type.eng.fl_str_mv article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
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/10.1002/art.34361
dc.identifier.uri.none.fl_str_mv https://repository.urosario.edu.co/handle/10336/22999
url https://doi.org/10.1002/art.34361
https://repository.urosario.edu.co/handle/10336/22999
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.citationEndPage.none.fl_str_mv 1969
dc.relation.citationIssue.none.fl_str_mv No. 6
dc.relation.citationStartPage.none.fl_str_mv 1960
dc.relation.citationTitle.none.fl_str_mv Arthritis and Rheumatism
dc.relation.citationVolume.none.fl_str_mv Vol. 64
dc.relation.ispartof.spa.fl_str_mv Arthritis and Rheumatism, Vol.64, No.6 (2012); pp. 1960-1969
dc.relation.uri.spa.fl_str_mv https://www.scopus.com/inward/record.uri?eid=2-s2.0-84861829947&doi=10.1002%2fart.34361&partnerID=40&md5=81773a26674913ac32a5a908ad336b4e
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.mimetype.none.fl_str_mv application/pdf
institution Universidad del Rosario
dc.source.instname.spa.fl_str_mv instname:Universidad del Rosario
dc.source.reponame.spa.fl_str_mv reponame:Repositorio Institucional EdocUR
repository.name.fl_str_mv Repositorio institucional EdocUR
repository.mail.fl_str_mv edocur@urosario.edu.co
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We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development. Methods Fifteen single-nucleotide polymorphisms (SNPs) across TRAF6 were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population-based case-control association analyses and meta-analyses were performed. P values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results Evidence of associations was detected in multiple SNPs. The best overall P values were obtained for SNPs rs5030437 and rs4755453 (P = 7.85 × 10 -5 and P = 4.73 × 10 -5, respectively) without significant heterogeneity among populations (P = 0.67 and P = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r 2 = 0.95) and demonstrated evidence of association with SLE in the same direction (meta-analysis P = 9.15 × 10 -4, OR 0.89 [95% CI 0.83-0.95]). The presence of thrombocytopenia improved the overall results in different populations (meta-analysis P = 1.99 × 10 -6, OR 0.57 [95% CI 0.45-0.72], for rs5030470). Finally, evidence of family-based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (P = 0.02) under a dominant model. Conclusion Our data indicate the presence of association of TRAF6 with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity. Copyright © 2012 by the American College of Rheumatology.application/pdfhttps://doi.org/10.1002/art.34361https://repository.urosario.edu.co/handle/10336/22999eng1969No. 61960Arthritis and RheumatismVol. 64Arthritis and Rheumatism, Vol.64, No.6 (2012); pp. 1960-1969https://www.scopus.com/inward/record.uri?eid=2-s2.0-84861829947&doi=10.1002%2fart.34361&partnerID=40&md5=81773a26674913ac32a5a908ad336b4eAbierto (Texto Completo)http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURTumor necrosis factor receptor associated factor 6African americanArticleCalculationControlled studyEthnicityFemaleGene linkage disequilibriumGenetic associationGenetic heterogeneityGenotypeHeredityHumanImmunityImmunopathogenesisMajor clinical studyMaleMeta analysis (topic)OrganogenesisPedigree analysisPopulation based case control studyPriority journalRheumatoid arthritisSignal transductionSingle nucleotide polymorphismSystemic lupus erythematosusThrombocytopeniaAllelesCase-control studiesCohort studiesFemaleGene frequencyGenetic association studiesGenetic predisposition to diseaseGenotypeHaplotypesHumansMaleTnf receptor-associated factor 6systemicsingle nucleotideLupus erythematosusPolymorphismEvaluation of TRAF6 in a large multiancestral lupus cohortarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Namjou, BahramChoi, Chan?BumHarley, Isaac T. W.Alarcón?Riquelme, Marta E.Kelly, Jennifer A.Glenn, Stuart B.Ojwang, Joshua O.Adler, AdamKim, KwangwooGallant, Caroline J.Boackle, Susan A.Criswell, Lindsey A.Kimberly, Robert P.Brown, Elizabeth E.Edberg, JeffreyAlarcón, Graciela S.Stevens, Anne M.Jacob, Chaim O.Gilkeson, Gary S.Kamen, Diane L.Tsao, Betty P.Kim, Eun?MiPark, So?YeonSung, Yoon?KyoungGuthridge, Joel M.Merrill, Joan T.Petri, MichelleRamsey?Goldman, RosalindVilá, Luis M.Niewold, Timothy B.Martin, JavierPons?Estel, Bernardo A.Vyse, Timothy J.Freedman, Barry I.Moser, Kathy L.Gaffney, Patrick M.Williams, Adrienne H.Comeau, Mary E.Reveille, John D.Kang, ChangwonJames, Judith A.Scofield, R. HalLangefeld, Carl D.Kaufman, Kenneth M.Harley, John B.Bae, Sang?CheolAnaya, Juan-Manuel10336/22999oai:repository.urosario.edu.co:10336/229992022-05-02 07:37:14.470347https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co