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Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups

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dc.creatorTan W.spa
dc.creatorSunahori K.spa
dc.creatorZhao J.spa
dc.creatorDeng Y.spa
dc.creatorKaufman K.M.spa
dc.creatorKelly J.A.spa
dc.creatorLangefeld C.D.spa
dc.creatorWilliams A.H.spa
dc.creatorComeau M.E.spa
dc.creatorZiegler J.T.spa
dc.creatorMarion M.C.spa
dc.creatorBae S.-C.spa
dc.creatorLee J.H.spa
dc.creatorLee J.-S.spa
dc.creatorChang D.-M.spa
dc.creatorSong Y.W.spa
dc.creatorYu C.-Y.spa
dc.creatorKimberly R.P.spa
dc.creatorEdberg J.C.spa
dc.creatorBrown E.E.spa
dc.creatorPetri M.A.spa
dc.creatorRamsey-Goldman R.spa
dc.creatorVilá L.M.spa
dc.creatorReveille J.D.spa
dc.creatorAlarcõn-Riquelme M.E.spa
dc.creatorHarley J.B.spa
dc.creatorBoackle S.A.spa
dc.creatorStevens A.M.spa
dc.creatorScofield R.H.spa
dc.creatorMerrill J.T.spa
dc.creatorFreedman B.I.spa
dc.creatorAnaya, Juan-Manuelspa
dc.creatorCriswell L.A.spa
dc.creatorJacob C.O.spa
dc.creatorVyse T.J.spa
dc.creatorNiewold T.B.spa
dc.creatorGaffney P.M.spa
dc.creatorMoser K.L.spa
dc.creatorGilkeson G.S.spa
dc.creatorKamen D.L.spa
dc.creatorJames J.A.spa
dc.creatorGrossman J.M.spa
dc.creatorHahn B.H.spa
dc.creatorTsokos G.C.spa
dc.creatorTsao B.P.spa
dc.date.accessioned2020-05-25T23:59:00Z
dc.date.available2020-05-25T23:59:00Z
dc.date.created2011spa
dc.description.abstractObjective T cells from patients with systemic lupus erythematosus (SLE) express increased amounts of PP2Ac, which contributes to decreased production of interleukin-2 (IL-2). Because IL-2 is important in the regulation of several aspects of the immune response, it has been proposed that PP2Ac contributes to the expression of SLE. This study was designed to determine whether genetic variants of PPP2AC are linked to the expression of SLE and specific clinical manifestations and account for the increased expression of PP2Ac. Methods We conducted a trans-ethnic study of 8,695 SLE cases and 7,308 controls of 4 different ancestries. Eighteen single-nucleotide polymorphisms (SNPs) across PPP2CA were genotyped using an Illumina custom array. PPP2CA expression in SLE and control T cells was analyzed by real-time polymerase chain reaction. Results A 32-kb haplotype comprising multiple SNPs of PPP2CA showed significant association with SLE in Hispanic Americans, European Americans, and Asians, but not in African Americans. Conditional analyses revealed that SNP rs7704116 in intron 1 showed consistently strong association with SLE across Asian, European American, and Hispanic American populations (odds ratio 1.3 [95% confidence interval 1.14-1.31], meta-analysis P = 3.8 × 10 -7). In European Americans, the largest ethnic data set studied, the risk A allele of rs7704116 was associated with the presence of renal disease, anti-double-stranded DNA, and anti-RNP antibodies. PPP2CA expression was ?2-fold higher in SLE patients carrying the rs7704116 AG genotype than those carrying the GG genotype (P = 0.007). Conclusion Our data provide the first evidence of an association between PPP2CA polymorphisms and elevated PP2Ac transcript levels in T cells, which implicates a new molecular pathway for SLE susceptibility in European Americans, Hispanic Americans, and Asians. Copyright © 2011 by the American College of Rheumatology.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1002/art.30452
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/22966
dc.language.isoengspa
dc.relation.citationEndPage2763
dc.relation.citationIssueNo. 9
dc.relation.citationStartPage2755
dc.relation.citationTitleArthritis and Rheumatism
dc.relation.citationVolumeVol. 63
dc.relation.ispartofArthritis and Rheumatism, Vol.63, No.9 (2011); pp. 2755-2763spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-80052316467&doi=10.1002%2fart.30452&partnerID=40&md5=b32facc20097ad6d77c9a5b0630f9ab5spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordDouble stranded DNA antibodyspa
dc.subject.keywordSystemiceng
dc.subject.keywordPhosphatasespa
dc.subject.keywordGeneticeng
dc.subject.keywordPPP2CA proteinspa
dc.subject.keywordRibonucleoprotein antibodyspa
dc.subject.keywordUnclassified drugspa
dc.subject.keywordAdultspa
dc.subject.keywordAfrican Americanspa
dc.subject.keywordAllelespa
dc.subject.keywordArticlespa
dc.subject.keywordAsianspa
dc.subject.keywordControlled studyspa
dc.subject.keywordDisease predispositionspa
dc.subject.keywordEthnic differencespa
dc.subject.keywordEuropean Americanspa
dc.subject.keywordFemalespa
dc.subject.keywordGene expressionspa
dc.subject.keywordGenetic associationspa
dc.subject.keywordGenetic polymorphismspa
dc.subject.keywordGenetic transcriptionspa
dc.subject.keywordGenetic variabilityspa
dc.subject.keywordGenotypespa
dc.subject.keywordHaplotypespa
dc.subject.keywordHispanicspa
dc.subject.keywordHumanspa
dc.subject.keywordIntronspa
dc.subject.keywordKidney diseasespa
dc.subject.keywordMajor clinical studyspa
dc.subject.keywordMalespa
dc.subject.keywordMicroarray analysisspa
dc.subject.keywordPriority journalspa
dc.subject.keywordReal time polymerase chain reactionspa
dc.subject.keywordRisk assessmentspa
dc.subject.keywordSingle nucleotide polymorphismspa
dc.subject.keywordSystemic lupus erythematosusspa
dc.subject.keywordT lymphocytespa
dc.subject.keywordAdolescentspa
dc.subject.keywordAdultspa
dc.subject.keywordAllelesspa
dc.subject.keywordAsian Continental Ancestry Groupspa
dc.subject.keywordEuropean Continental Ancestry Groupspa
dc.subject.keywordFemalespa
dc.subject.keywordGenetic Association Studiesspa
dc.subject.keywordGenetic Predisposition to Diseasespa
dc.subject.keywordGenotypespa
dc.subject.keywordHaplotypesspa
dc.subject.keywordHispanic Americansspa
dc.subject.keywordHumansspa
dc.subject.keywordInterleukin-2spa
dc.subject.keywordLupus Erythematosuseng
dc.subject.keywordMalespa
dc.subject.keywordMiddle Agedspa
dc.subject.keywordPolymorphismeng
dc.subject.keywordProtein Phosphatase 2spa
dc.subject.keywordT-Lymphocytesspa
dc.titleAssociation of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groupsspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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