Genetic association of CD247 (CD3?) with SLE in a large-scale multiethnic study

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3? chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3? are not well established and require replication in indepe...

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Autores:
Tipo de recurso:
Fecha de publicación:
2015
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/24137
Acceso en línea:
https://doi.org/10.1038/gene.2014.73
https://repository.urosario.edu.co/handle/10336/24137
Palabra clave:
CD247 antigen
T lymphocyte antigen
Unclassified drug
CD3 antigen
Adult
African
American Indian
Article
Asian
Chromosome 1
Controlled study
Ethnic difference
European
Female
Gene frequency
Gene locus
Genetic association
Genetic model
Genetic variability
Genotype
Haplotype
Haplotype map
Heterozygosity
Hispanic
Human
Immunopathogenesis
Major clinical study
Male
Molecular pathology
Priority journal
Single nucleotide polymorphism
Systemic lupus erythematosus
Asian continental ancestry group
Case control study
Caucasian
Ethnology
Genetic association study
Genetic predisposition
Genetics
Immunology
Single nucleotide polymorphism
Systemic lupus erythematosus
T lymphocyte
Adult
Asian Continental Ancestry Group
Case-Control Studies
European Continental Ancestry Group
Female
Genetic Association Studies
Genetic Predisposition to Disease
Haplotypes
Humans
Male
T-Lymphocytes
CD3
Single Nucleotide
zeta chain
Systemic
CD3 antigen
Antigens
Lupus Erythematosus
Polymorphism
Rights
License
Abierto (Texto Completo)
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dc.title.spa.fl_str_mv Genetic association of CD247 (CD3?) with SLE in a large-scale multiethnic study
title Genetic association of CD247 (CD3?) with SLE in a large-scale multiethnic study
spellingShingle Genetic association of CD247 (CD3?) with SLE in a large-scale multiethnic study
CD247 antigen
T lymphocyte antigen
Unclassified drug
CD3 antigen
Adult
African
American Indian
Article
Asian
Chromosome 1
Controlled study
Ethnic difference
European
Female
Gene frequency
Gene locus
Genetic association
Genetic model
Genetic variability
Genotype
Haplotype
Haplotype map
Heterozygosity
Hispanic
Human
Immunopathogenesis
Major clinical study
Male
Molecular pathology
Priority journal
Single nucleotide polymorphism
Systemic lupus erythematosus
Asian continental ancestry group
Case control study
Caucasian
Ethnology
Genetic association study
Genetic predisposition
Genetics
Immunology
Single nucleotide polymorphism
Systemic lupus erythematosus
T lymphocyte
Adult
Asian Continental Ancestry Group
Case-Control Studies
European Continental Ancestry Group
Female
Genetic Association Studies
Genetic Predisposition to Disease
Haplotypes
Humans
Male
T-Lymphocytes
CD3
Single Nucleotide
zeta chain
Systemic
CD3 antigen
Antigens
Lupus Erythematosus
Polymorphism
title_short Genetic association of CD247 (CD3?) with SLE in a large-scale multiethnic study
title_full Genetic association of CD247 (CD3?) with SLE in a large-scale multiethnic study
title_fullStr Genetic association of CD247 (CD3?) with SLE in a large-scale multiethnic study
title_full_unstemmed Genetic association of CD247 (CD3?) with SLE in a large-scale multiethnic study
title_sort Genetic association of CD247 (CD3?) with SLE in a large-scale multiethnic study
dc.subject.keyword.spa.fl_str_mv CD247 antigen
T lymphocyte antigen
Unclassified drug
CD3 antigen
Adult
African
American Indian
Article
Asian
Chromosome 1
Controlled study
Ethnic difference
European
Female
Gene frequency
Gene locus
Genetic association
Genetic model
Genetic variability
Genotype
Haplotype
Haplotype map
Heterozygosity
Hispanic
Human
Immunopathogenesis
Major clinical study
Male
Molecular pathology
Priority journal
Single nucleotide polymorphism
Systemic lupus erythematosus
Asian continental ancestry group
Case control study
Caucasian
Ethnology
Genetic association study
Genetic predisposition
Genetics
Immunology
Single nucleotide polymorphism
Systemic lupus erythematosus
T lymphocyte
Adult
Asian Continental Ancestry Group
Case-Control Studies
European Continental Ancestry Group
Female
Genetic Association Studies
Genetic Predisposition to Disease
Haplotypes
Humans
Male
T-Lymphocytes
topic CD247 antigen
T lymphocyte antigen
Unclassified drug
CD3 antigen
Adult
African
American Indian
Article
Asian
Chromosome 1
Controlled study
Ethnic difference
European
Female
Gene frequency
Gene locus
Genetic association
Genetic model
Genetic variability
Genotype
Haplotype
Haplotype map
Heterozygosity
Hispanic
Human
Immunopathogenesis
Major clinical study
Male
Molecular pathology
Priority journal
Single nucleotide polymorphism
Systemic lupus erythematosus
Asian continental ancestry group
Case control study
Caucasian
Ethnology
Genetic association study
Genetic predisposition
Genetics
Immunology
Single nucleotide polymorphism
Systemic lupus erythematosus
T lymphocyte
Adult
Asian Continental Ancestry Group
Case-Control Studies
European Continental Ancestry Group
Female
Genetic Association Studies
Genetic Predisposition to Disease
Haplotypes
Humans
Male
T-Lymphocytes
CD3
Single Nucleotide
zeta chain
Systemic
CD3 antigen
Antigens
Lupus Erythematosus
Polymorphism
dc.subject.keyword.eng.fl_str_mv CD3
Single Nucleotide
zeta chain
Systemic
CD3 antigen
Antigens
Lupus Erythematosus
Polymorphism
description A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3? chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3? are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10-4 less than P less than 4.15 × 10-2), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P less than inf>hap less than /inf> = 2.12 × 10-5) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls=13%; P=4.99 × 10-4, odds ratio=1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P less than 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10-3 less than P less than 3.97 × 10-2), with one (rs704848) remaining significant after Bonferroni correction (P less than inf>meta less than /inf> =2.66 × 10-2). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism. © 2015 Macmillan Publishers Limited.
publishDate 2015
dc.date.created.spa.fl_str_mv 2015
dc.date.accessioned.none.fl_str_mv 2020-05-26T00:09:06Z
dc.date.available.none.fl_str_mv 2020-05-26T00:09:06Z
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/10.1038/gene.2014.73
dc.identifier.issn.none.fl_str_mv 14664879
14765470
dc.identifier.uri.none.fl_str_mv https://repository.urosario.edu.co/handle/10336/24137
url https://doi.org/10.1038/gene.2014.73
https://repository.urosario.edu.co/handle/10336/24137
identifier_str_mv 14664879
14765470
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.citationEndPage.none.fl_str_mv 150
dc.relation.citationIssue.none.fl_str_mv No. 2
dc.relation.citationStartPage.none.fl_str_mv 142
dc.relation.citationTitle.none.fl_str_mv Genes and Immunity
dc.relation.citationVolume.none.fl_str_mv Vol. 16
dc.relation.ispartof.spa.fl_str_mv Genes and Immunity, ISSN:14664879, 14765470, Vol.16, No.2 (2015); pp. 142-150
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However, genetic associations with SLE in the human CD247 locus that encodes CD3? are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10-4 less than P less than 4.15 × 10-2), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P less than inf>hap less than /inf> = 2.12 × 10-5) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls=13%; P=4.99 × 10-4, odds ratio=1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P less than 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10-3 less than P less than 3.97 × 10-2), with one (rs704848) remaining significant after Bonferroni correction (P less than inf>meta less than /inf> =2.66 × 10-2). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism. © 2015 Macmillan Publishers Limited.application/pdfhttps://doi.org/10.1038/gene.2014.731466487914765470https://repository.urosario.edu.co/handle/10336/24137engNature Publishing Group150No. 2142Genes and ImmunityVol. 16Genes and Immunity, ISSN:14664879, 14765470, Vol.16, No.2 (2015); pp. 142-150https://www.scopus.com/inward/record.uri?eid=2-s2.0-84938552405&doi=10.1038%2fgene.2014.73&partnerID=40&md5=43f256c80a96fdd4f209c9ea1a3c2690Abierto (Texto Completo)http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURCD247 antigenT lymphocyte antigenUnclassified drugCD3 antigenAdultAfricanAmerican IndianArticleAsianChromosome 1Controlled studyEthnic differenceEuropeanFemaleGene frequencyGene locusGenetic associationGenetic modelGenetic variabilityGenotypeHaplotypeHaplotype mapHeterozygosityHispanicHumanImmunopathogenesisMajor clinical studyMaleMolecular pathologyPriority journalSingle nucleotide polymorphismSystemic lupus erythematosusAsian continental ancestry groupCase control studyCaucasianEthnologyGenetic association studyGenetic predispositionGeneticsImmunologySingle nucleotide polymorphismSystemic lupus erythematosusT lymphocyteAdultAsian Continental Ancestry GroupCase-Control StudiesEuropean Continental Ancestry GroupFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHaplotypesHumansMaleT-LymphocytesCD3Single Nucleotidezeta chainSystemicCD3 antigenAntigensLupus ErythematosusPolymorphismGenetic association of CD247 (CD3?) with SLE in a large-scale multiethnic studyarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Martins, MWilliams, A HComeau, MMarion, MZiegler, J TFreedman, B IMerrill, J TGlenn, S BKelly, J ASivils, K MJames, J AGuthridge, J MAlarcón-Riquelme, M EBae, S-CKim, J-HKim, DAnaya, Juan-ManuelBoackle, S ACriswell, L AKimberly, R PAlarcón, G SBrown, E EVilá, L MPetri, M ARamsey-Goldman, RNiewold, T BTsao, B PGilkeson, G SKamen, D LJacob, C OStevens, A MGaffney, P MHarley, J BLangefeld, C DFesel, CORIGINALgene201473.pdfapplication/pdf1434574https://repository.urosario.edu.co/bitstreams/ad49f285-a5f9-4f91-afe7-22b4163b4898/downloadb2b6c895054af8681650ed9006f63ad6MD51TEXTgene201473.pdf.txtgene201473.pdf.txtExtracted texttext/plain49948https://repository.urosario.edu.co/bitstreams/5ae5a935-7d2d-4feb-9dea-122882333ba6/download9fa04ed05d67ad55e3f9eaf2efde062aMD52THUMBNAILgene201473.pdf.jpggene201473.pdf.jpgGenerated Thumbnailimage/jpeg4809https://repository.urosario.edu.co/bitstreams/47cf4c48-920b-40e3-b9f0-30765c826045/downloadb11be084458dd461e63547d71d1a713fMD5310336/24137oai:repository.urosario.edu.co:10336/241372022-05-02 07:37:13.475654https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co