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Fine mapping of Xq28: Both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groups

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dc.creatorKaufman, Kenneth Mspa
dc.creatorZhao, Jianspa
dc.creatorKelly, Jennifer Aspa
dc.creatorHughes, Travisspa
dc.creatorAdler, Adamspa
dc.creatorSanchez, Elenaspa
dc.creatorOjwang, Joshua Ospa
dc.creatorLangefeld, Carl Dspa
dc.creatorZiegler, Julie Tspa
dc.creatorWilliams, Adrienne Hspa
dc.creatorComeau, Mary Espa
dc.creatorMarion, Miranda Cspa
dc.creatorGlenn, Stuart Bspa
dc.creatorCantor, Rita Mspa
dc.creatorGrossman, Jennifer Mspa
dc.creatorHahn, Bevra Hspa
dc.creatorSong, Yeong Wookspa
dc.creatorYu, Chack-Yungspa
dc.creatorJames, Judith Aspa
dc.creatorGuthridge, Joel Mspa
dc.creatorBrown, Elizabeth Espa
dc.creatorAlarcón, Graciela Sspa
dc.creatorKimberly, Robert Pspa
dc.creatorEdberg, Jeffrey Cspa
dc.creatorRamsey-Goldman, Rosalindspa
dc.creatorPetri, Michelle Aspa
dc.creatorReveille, John Dspa
dc.creatorVilá, Luis Mspa
dc.creatorAnaya, Juan-Manuelspa
dc.creatorBoackle, Susan Aspa
dc.creatorStevens, Anne Mspa
dc.creatorFreedman, Barry Ispa
dc.creatorCriswell, Lindsey Aspa
dc.creatorPons Estel, Bernardo Aspa
dc.creatorLee, Joo-Hyunspa
dc.creatorLee, Ji-Seonspa
dc.creatorChang, Deh-Mingspa
dc.creatorScofield, R Hal Aspa
dc.creatorGilkeson, Gary Sspa
dc.creatorMerrill, Joan Tspa
dc.creatorNiewold, Timothy Bspa
dc.creatorVyse, Timothy Jamesspa
dc.creatorBae, Sang-Cheolspa
dc.creatorAlarcón-Riquelme, Marta Espa
dc.creatorJacob, Chaim Ospa
dc.creatorMoser Sivils, Kathyspa
dc.creatorGaffney, Patrick Mspa
dc.creatorHarley, John Bspa
dc.creatorSawalha, Amr Hspa
dc.creatorTsao, Betty Pspa
dc.date.accessioned2020-05-25T23:56:26Z
dc.date.available2020-05-25T23:56:26Z
dc.date.created2013spa
dc.description.abstractObjectives: The Xq28 region containing IRAK1 and MECP2 has been identified as a risk locus for systemic lupus erythematosus (SLE) in previous genetic association studies. However, due to the strong linkage disequilibrium between IRAK1 and MECP2, it remains unclear which gene is affected by the underlying causal variant (s) conferring risk of SLE. Methods: We fine-mapped ?136 SNPs in a ?227 kb region on Xq28, containing IRAK1, MECP2 and seven adjacent genes (L1CAM, AVPR2, ARHGAP4, NAA10, RENBP HCFC1 and TMEM187), for association with SLE in 15 783 case-control subjects derived from four different ancestral groups. Results: Multiple SNPs showed strong association with SLE in European Americans, Asians and Hispanics at p and lt;5×10-8 with consistent association in subjects with African ancestry. Of these, six SNPs located in the TMEM187-IRAK1-MECP2 region captured the underlying causal variant(s) residing in a common risk haplotype shared by all four ancestral groups. Among them, rs1059702 best explained the Xq28 association signals in conditional testings and exhibited the strongest p value in transancestral meta-analysis (p meta=1.3×10-27, OR=1.43), and thus was considered to be the most likely causal variant. The risk allele of rs1059702 results in the amino acid substitution S196F in IRAK1 and had previously been shown to increase NF-KB activity in vitro. We also found that the homozygous risk genotype of rs1059702 was associated with lower mRNA levels of MECP2, but not IRAK1, in SLE patients (p=0.0012) and healthy controls (p=0.0064). Conclusions: These data suggest contributions of both IRAK1 and MECP2 to SLE susceptibility.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1136/annrheumdis-2012-201851
dc.identifier.issn00034967
dc.identifier.issn14682060
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/22422
dc.language.isoengspa
dc.relation.citationEndPage444
dc.relation.citationIssueNo. 3
dc.relation.citationStartPage437
dc.relation.citationTitleAnnals of the Rheumatic Diseases
dc.relation.citationVolumeVol. 72
dc.relation.ispartofAnnals of the Rheumatic Diseases, ISSN:00034967, 14682060, Vol.72, No.3 (2013); pp. 437-444spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84873744778&doi=10.1136%2fannrheumdis-2012-201851&partnerID=40&md5=3e85de92d464712bb9fac98bb8f6865cspa
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.keywordImmunoglobulin enhancer binding proteinspa
dc.subject.keywordInterleukin 1 receptor associated kinase 1spa
dc.subject.keywordsystemiceng
dc.subject.keywordsingle nucleotideeng
dc.subject.keywordhumaneng
dc.subject.keywordMessenger rnaspa
dc.subject.keywordMethyl cpg binding protein 2spa
dc.subject.keywordAmino acid substitutionspa
dc.subject.keywordArhgap4 genespa
dc.subject.keywordArticlespa
dc.subject.keywordAsianspa
dc.subject.keywordAvpr2 genespa
dc.subject.keywordCase control studyspa
dc.subject.keywordChromosome xqspa
dc.subject.keywordChromosome xq28spa
dc.subject.keywordControlled studyspa
dc.subject.keywordEthnic differencespa
dc.subject.keywordEuropean americanspa
dc.subject.keywordGenespa
dc.subject.keywordGene locationspa
dc.subject.keywordGene mappingspa
dc.subject.keywordGenetic associationspa
dc.subject.keywordGenetic riskspa
dc.subject.keywordGenetic susceptibilityspa
dc.subject.keywordGenotypespa
dc.subject.keywordHaplotypespa
dc.subject.keywordHcfc1 genespa
dc.subject.keywordHispanicspa
dc.subject.keywordHumanspa
dc.subject.keywordIrak1 genespa
dc.subject.keywordL1cam genespa
dc.subject.keywordMajor clinical studyspa
dc.subject.keywordMecp2 genespa
dc.subject.keywordNaa10 genespa
dc.subject.keywordNegrospa
dc.subject.keywordPlesiomorphyspa
dc.subject.keywordPriority journalspa
dc.subject.keywordProtein functionspa
dc.subject.keywordReal time polymerase chain reactionspa
dc.subject.keywordRenbp genespa
dc.subject.keywordSingle nucleotide polymorphismspa
dc.subject.keywordSystemic lupus erythematosusspa
dc.subject.keywordTmem187 genespa
dc.subject.keywordBase sequencespa
dc.subject.keywordChromosome mappingspa
dc.subject.keywordChromosomeseng
dc.subject.keywordContinental population groupsspa
dc.subject.keywordGenetic predisposition to diseasespa
dc.subject.keywordGenotypespa
dc.subject.keywordHaplotypesspa
dc.subject.keywordHumansspa
dc.subject.keywordInterleukin-1 receptor-associated kinasesspa
dc.subject.keywordLupus erythematosuseng
dc.subject.keywordMethyl-cpg-binding protein 2spa
dc.subject.keywordMolecular sequence dataspa
dc.subject.keywordPolymorphismeng
dc.subject.keywordReal-time polymerase chain reactionspa
dc.subject.keywordRisk factorsspa
dc.titleFine mapping of Xq28: Both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groupsspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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