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dc.creatorDeng, Yun 
dc.creatorZhao, Jian 
dc.creatorSakurai, Daisuke 
dc.creatorSestak, Andrea L 
dc.creatorOsadchiy, Vadim 
dc.creatorLangefeld, Carl D 
dc.creatorKaufman, Kenneth M 
dc.creatorKelly, Jennifer A 
dc.creatorJames, Judith A 
dc.creatorPetri, Michelle A 
dc.creatorBae, Sang-Cheol 
dc.creatorAlarcón-Riquelme, Marta E 
dc.creatorAlarcón, Graciela S 
dc.creatorAnaya, Juan-Manuel 
dc.creatorCriswell, Lindsey A 
dc.creatorFreedman, Barry I 
dc.creatorKamen, Diane L 
dc.creatorGilkeson, Gary S 
dc.creatorJacob, Chaim O 
dc.creatorMerrill, Joan T 
dc.creatorGaffney, Patrick M 
dc.creatorSivils, Kathy Moser 
dc.creatorNiewold, Timothy B 
dc.creatorRamsey-Goldman, Rosalind 
dc.creatorReveille, John D 
dc.creatorScofield, R Hal 
dc.creatorStevens, Anne M 
dc.creatorBoackle, Susan A 
dc.creatorVilá, Luis M 
dc.creatorSohn, I I Woong 
dc.creatorLee, Seung 
dc.creatorChang, Deh-Ming 
dc.creatorSong, Yeong Wook 
dc.creatorVyse, Timothy J 
dc.creatorHarley, John B 
dc.creatorBrown, Elizabeth E 
dc.creatorEdberg, Jeffrey C 
dc.creatorKimberly, Robert P 
dc.creatorCantor, Rita M 
dc.creatorHahn, Bevra H 
dc.creatorGrossman, Jennifer M 
dc.creatorTsao, Betty P 
dc.date.accessioned2020-05-25T23:56:33Z
dc.date.available2020-05-25T23:56:33Z
dc.date.created2016
dc.identifier.issn00034967
dc.identifier.issn14682060
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/22456
dc.description.abstract"Objectives Following up the systemic lupus erythematosus (SLE) genome-wide association studies (GWAS) identification of NMNAT2 at rs2022013, we fine-mapped its 150a €...kb flanking regions containing NMNAT2 and SMG7 in a 15a €...292 case-control multi-ancestry population and tested functions of identified variants. Methods We performed genotyping using custom array, imputation by IMPUTE 2.1.2 and allele specific functions using quantitative real-time PCR and luciferase reporter transfections. SLE peripheral blood mononuclear cells (PBMCs) were cultured with small interfering RNAs to measure antinuclear antibody (ANA) and cyto/chemokine levels in supernatants using ELISA. Results We confirmed association at NMNAT2 in European American (EA) and Amerindian/Hispanic ancestries, and identified independent signal at SMG7 tagged by rs2702178 in EA only (p=2.4×10 a '8, OR=1.23 (95% CI 1.14 to 1.32)). In complete linkage disequilibrium with rs2702178, rs2275675 in the promoter region robustly associated with SMG7 mRNA levels in multiple expression quantitative trait locus (eQTL) datasets. Its risk allele was dose-dependently associated with decreased SMG7 mRNA levels in PBMCs of 86 patients with SLE and 119 controls (p=1.1×10 a '3 and 6.8×10 a '8, respectively) and conferred reduced transcription activity in transfected HEK-293 (human embryonic kidney cell line) and Raji cells (p=0.0035 and 0.0037, respectively). As a critical component in the nonsense-mediated mRNA decay pathway, SMG7 could regulate autoantigens including ribonucleoprotein (RNP) and Smith (Sm). We showed SMG7 mRNA levels in PBMCs correlated inversely with ANA titres of patients with SLE (r=a '0.31, p=0.01), and SMG7 knockdown increased levels of ANA IgG and chemokine (C-C motif) ligand 19 in SLE PBMCs (p=2.0×10 a '5 and 2.0×10 a '4, respectively). Conclusion We confirmed NMNAT2 and identified independent SMG7 association with SLE. The inverse relationship between levels of the risk allele-associated SMG7 mRNAs and ANA suggested the novel contribution of mRNA surveillance pathway to SLE pathogenesis. © 2016 Published by the BMJ Publishing Group Limited."
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.relation.ispartofAnnals of the Rheumatic Diseases, ISSN:00034967, 14682060, Vol.75, No.11 (2016); pp. 2007-2013
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84956688448&doi=10.1136%2fannrheumdis-2015-208441&partnerID=40&md5=99327f1cad95fc1b593eb80bc79030c1
dc.sourceinstname:Universidad del Rosario
dc.sourcereponame:Repositorio Institucional EdocUR
dc.titleDecreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production
dc.typearticle
dc.publisherBMJ Publishing Group
dc.subject.keywordAntinuclear antibody
dc.subject.keywordsystemic
dc.subject.keywordImmunoglobulin g
dc.subject.keywordantinuclear
dc.subject.keywordhuman
dc.subject.keywordhuman
dc.subject.keywordmessenger
dc.subject.keywordmononuclear
dc.subject.keywordRibonucleoprotein antibody
dc.subject.keywordSm antibody
dc.subject.keywordSmall interfering rna
dc.subject.keywordAntinuclear antibody
dc.subject.keywordCarrier protein
dc.subject.keywordMessenger rna
dc.subject.keywordNicotinamide nucleotide adenylyltransferase
dc.subject.keywordNmnat2 protein
dc.subject.keywordSmg7 protein
dc.subject.keywordAllele
dc.subject.keywordAntibody production
dc.subject.keywordAntibody titer
dc.subject.keywordArticle
dc.subject.keywordCase control study
dc.subject.keywordCell culture
dc.subject.keywordControlled study
dc.subject.keywordCorrelational study
dc.subject.keywordEmbryo
dc.subject.keywordEthnic difference
dc.subject.keywordGene
dc.subject.keywordGene expression
dc.subject.keywordGene function
dc.subject.keywordGene linkage disequilibrium
dc.subject.keywordGene silencing
dc.subject.keywordGenetic association
dc.subject.keywordGenetic transcription
dc.subject.keywordGenetic variability
dc.subject.keywordGenotype
dc.subject.keywordHuman
dc.subject.keywordHuman cell
dc.subject.keywordLuciferase assay
dc.subject.keywordMajor clinical study
dc.subject.keywordMulticenter study (topic)
dc.subject.keywordNmnat2 gene
dc.subject.keywordPeripheral blood mononuclear cell
dc.subject.keywordPriority journal
dc.subject.keywordPromoter region
dc.subject.keywordQuantitative trait locus
dc.subject.keywordRaji cell line
dc.subject.keywordReal time polymerase chain reaction
dc.subject.keywordRegulatory mechanism
dc.subject.keywordRisk
dc.subject.keywordSingle nucleotide polymorphism
dc.subject.keywordSmg7 gene
dc.subject.keywordSystemic lupus erythematosus
dc.subject.keywordAmerican indian
dc.subject.keywordCaucasian
dc.subject.keywordFemale
dc.subject.keywordGenetic predisposition
dc.subject.keywordGenetics
dc.subject.keywordGenome-wide association study
dc.subject.keywordGenotyping technique
dc.subject.keywordHek293 cell line
dc.subject.keywordHispanic
dc.subject.keywordImmunology
dc.subject.keywordMale
dc.subject.keywordMetabolism
dc.subject.keywordMononuclear cell
dc.subject.keywordPedigree
dc.subject.keywordRisk factor
dc.subject.keywordSystemic lupus erythematosus
dc.subject.keywordAlleles
dc.subject.keywordAmerican native continental ancestry group
dc.subject.keywordAntibodies
dc.subject.keywordCarrier proteins
dc.subject.keywordEuropean continental ancestry group
dc.subject.keywordFemale
dc.subject.keywordGenetic predisposition to disease
dc.subject.keywordGenome-wide association study
dc.subject.keywordGenotyping techniques
dc.subject.keywordHek293 cells
dc.subject.keywordHispanic americans
dc.subject.keywordHumans
dc.subject.keywordLeukocytes
dc.subject.keywordLinkage disequilibrium
dc.subject.keywordLupus erythematosus
dc.subject.keywordMale
dc.subject.keywordNicotinamide-nucleotide adenylyltransferase
dc.subject.keywordPedigree
dc.subject.keywordReal-time polymerase chain reaction
dc.subject.keywordRisk factors
dc.subject.keywordRna
dc.subject.keywordAutoantibodies
dc.subject.keywordGene polymorphism
dc.subject.keywordSystemic lupus erythematosus
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.type.spaArtículo
dc.rights.accesoAbierto (Texto Completo)
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doihttps://doi.org/10.1136/annrheumdis-2015-208441
dc.relation.citationEndPage2013
dc.relation.citationIssueNo. 11
dc.relation.citationStartPage2007
dc.relation.citationTitleAnnals of the Rheumatic Diseases
dc.relation.citationVolumeVol. 75


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