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Genetic association of CD247 (CD3ΞΆ) with SLE in a large-scale multiethnic study

2015-03Journal article Open access
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dc.contributor.authorMartins, M
dc.contributor.authorWilliams, A H
dc.contributor.authorComeau, M
dc.contributor.authorMarion, M
dc.contributor.authorZiegler, J T
dc.contributor.authorFreedman, B I
dc.contributor.authorMerrill, J T
dc.contributor.authorGlenn, S B
dc.contributor.authorKelly, J A
dc.contributor.authorSivils, K M
dc.contributor.authorJames, J A
dc.contributor.authorGuthridge, J M
dc.contributor.authorAlarcΓ³n-Riquelme, M E
dc.contributor.authorBae, S-C
dc.contributor.authorKim, J-H
dc.contributor.authorKim, D
dc.contributor.authorAnaya, J-M
dc.contributor.authorBoackle, S A
dc.contributor.authorCriswell, L A
dc.contributor.authorKimberly, R P
dc.contributor.authorAlarcΓ³n, G S
dc.contributor.authorBrown, E E
dc.contributor.authorVilΓ‘, L M
dc.contributor.authorPetri, M A
dc.contributor.authorRamsey-Goldman, R
dc.contributor.authorNiewold, T B
dc.contributor.authorTsao, B P
dc.contributor.authorGilkeson, G S
dc.contributor.authorKamen, D L
dc.contributor.authorJacob, C O
dc.contributor.authorStevens, A M
dc.contributor.authorGaffney, P M
dc.contributor.authorHarley, J B
dc.contributor.authorLangefeld, C D
dc.contributor.authorFesel, C
dc.date.accessioned2016-07-08T12:20:50Z
dc.date.available2016-07-08T12:20:50Z
dc.date.issued2015-03
dc.description.abstractA classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ΞΆ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ΞΆ 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 Γ— 10(-4) < P < 4.15 Γ— 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 Γ— 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 Γ— 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 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 Γ— 10(-3) < P< 3.97 Γ— 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 Γ— 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.pt_PT
dc.description.sponsorshipNational Institutes of Health grants: (UL1RR025741, K24AR002138, P602AR30692, P01AR49084, UL1TR000165, P01AI083194, RO1AR43814, P60AR053308, UL1TR000004, AR43727, R21AI070304, RO1AR057172, UL1RR025014, R01AR051545-03, UL1RR029882, P60AR062755, P30AR53483, U19AI082714, P30GM103510, U01AI101934, AI063274, AR056360, AI083194, R37AI024717, P01083194, P01AR049084, PR094002); Northwestern University Feinberg School of Medicine; University of Alabama Birmingham; National Institute of Arthritis and Musculoskeletal and Skin Diseases; University of California Los Angeles; University of California San Francisco; Hopkins University; University of Colorado School of Medicine; University of Southern California; Seattle Children's Research Institute Arthritis Foundation; Medical University of South Carolina; Oklahoma Medical Research Foundation; Cincinnati Children's Hospital Medical Center; US Departments of Defense grant: (PR094002); Veterans Affairs; Alliance for Lupus Research; Kirkland Scholar Award; Korea Healthcare technology R & D project: (A121983); Ministry for Health and Welfare; Republic of Korea; Swedish Research Council; Instituto de Salud Carlos III grant: (PS09/00129); European Union FEDER funds; Fundação para a CiΓͺncia e Tecnologia fellowships: (SFRH/BPD/29354/2006, SFRH/BPD/34648/2007).pt_PT
dc.identifier.citationMartins, M., Williams, A. H., Comeau, M., Marion, M., Ziegler, J. T., Freedman, B. I., Merrill, J. T., Glenn, S. B., Kelly, J. A., Sivils, K. M., James, J. A., Guthridge, J. M., AlarcΓ³n-Riquelme, M. E., Bae, S.-C., Kim, J.-H., Kim, D., Anaya, J.-M., Boackle, S. A., Criswell, L. A., Kimberly, R. P., AlarcΓ³n, G. S., Brown, E. E., VilΓ‘, L. M., Petri, M. A., Ramsey-Goldman, R., Niewold, T. B., Tsao, B. P., Gilkeson, G. S., Kamen, D. L., Jacob, C. O., Stevens, A. M., Gaffney, P. M., Harley, J. B., Langefeld, C. D., Fesel, C. (2015). Genetic association of CD247 (CD3ΞΆ) with SLE in a large-scale multiethnic study. Genes Immun, 16(2), 142–150.pt_PT
dc.identifier.doi10.1038/gene.2014.73pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/678
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherNature Publishing Grouppt_PT
dc.subjectAdultpt_PT
dc.subjectAntigens, CD3pt_PT
dc.subjectAsian Continental Ancestry Grouppt_PT
dc.subjectCase-Control Studiespt_PT
dc.subjectEuropean Continental Ancestry Grouppt_PT
dc.subjectFemalept_PT
dc.subjectGenetic Association Studiespt_PT
dc.subjectGenetic Predisposition to Diseasept_PT
dc.subjectHaplotypespt_PT
dc.subjectHumanspt_PT
dc.subjectLupus Erythematosus, Systemicpt_PT
dc.subjectMalept_PT
dc.subjectPolymorphism, Single Nucleotidept_PT
dc.subjectT-Lymphocytespt_PT
dc.titleGenetic association of CD247 (CD3ΞΆ) with SLE in a large-scale multiethnic studypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage150pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage142pt_PT
oaire.citation.titleGenes and Immunitypt_PT
oaire.citation.volume16pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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