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dc.creatorVaughn, Samuel E. 
dc.creatorFoley, Corinne 
dc.creatorLu, Xiaoming 
dc.creatorPatel, Zubin H. 
dc.creatorZoller, Erin E. 
dc.creatorMagnusen, Albert F. 
dc.creatorWilliams, Adrienne H. 
dc.creatorZiegler, Julie T. 
dc.creatorComeau, Mary E. 
dc.creatorMarion, Miranda C. 
dc.creatorTsao, Betty P. 
dc.creatorJacob, Chaim O. 
dc.creatorKamen, Diane L. 
dc.creatorBrown, Elizabeth E. 
dc.creatorGikenson, Gary S. 
dc.creatorAlarcón, Graciela S. 
dc.creatorReveille, John D. 
dc.creatorAnaya, Juan-Manuel 
dc.creatorJames, Judith A. 
dc.creatorMoser, Kathy L. 
dc.creatorCriswell, Lindsey A. 
dc.creatorVilá, Luis M. 
dc.creatorAlarcon-Riquelme, Marta E. 
dc.creatorPetri, Michelle 
dc.creatorScofield, R. Hal 
dc.creatorKimberly, Robert P. 
dc.creatorBinjoo, Young 
dc.creatorChoi, Jeongim 
dc.creatorBae, Sang-Cheol 
dc.creatorBoackle, Susan A. 
dc.creatorVyse, Timothy J. 
dc.creatorGuthridge, Joel M. 
dc.creatorNamjou, Bahram 
dc.creatorGaffney, Patrick M. 
dc.creatorLangefeld, Carl D. 
dc.creatorKaufman, Kenneth M. 
dc.creatorKelly, Jennifer A. 
dc.creatorHarley, Isaac T.W. 
dc.creatorHarley, John B. 
dc.creatorKottyan, Leah C. 
dc.date.accessioned2020-04-27T22:47:16Z
dc.date.available2020-04-27T22:47:16Z
dc.date.created2014
dc.date.issued2014
dc.identifier.issn1664-8021
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/21786
dc.description.abstractGenome wide association studies have identified variants in PXK that confer risk for humoral autoimmune diseases, including systemic lupus erythematosus (SLE or lupus), rheumatoid arthritis and more recently systemic sclerosis. While PXK is involved in trafficking of epidermal growth factor Receptor (EGFR) in COS-7 cells, mechanisms linking PXK to lupus pathophysiology have remained undefined. In an effort to uncover the mechanism at this locus that increases lupus-risk, we undertook a fine-mapping analysis in a large multi-ancestral study of lupus patients and controls. We define a large (257kb) common haplotype marking a single causal variant that confers lupus risk detected only in European ancestral populations and spans the promoter through the 3' UTR of PXK. The strongest association was found at rs6445972 with P < 4.62 × 10-10, OR 0.81 (0.75 - 0.86). Using stepwise logistic regression analysis, we demonstrate that one signal drives the genetic association in the region. Bayesian analysis confirms our results, identifying a 95% credible set consisting of 172 variants spanning 202 kb. Functionally, we found that PXK operates on the B-cell antigen receptor (BCR); we confirmed that PXK influenced the rate of BCR internalization. Furthermore, we demonstrate that individuals carrying the risk haplotype exhibited a decreased rate of BCR internalization, a process known to impact B cell survival and cell fate. Taken together, these data define a new candidate mechanism for the genetic association of variants around PXK with lupus risk and highlight the regulation of intracellular trafficking as a genetically regulated pathway mediating human autoimmunity.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.relation.ispartofFrontiers in Genetics, ISSN: 1664-8021 Vol. 5, No. DEC (2014)
dc.relation.urihttps://www.frontiersin.org/articles/10.3389/fgene.2014.00450/full
dc.subject.ddcEnfermedades 
dc.titleLupus risk variants in the PXK locus alter B-cell receptor internalization
dc.typearticle
dc.subject.keywordlupus
dc.subject.keywordPXK
dc.subject.keywordfine-mapping
dc.subject.keywordB cells
dc.subject.keywordBCR
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.type.spaArtículo
dc.rights.accesoAbierto (Texto Completo)
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.creator.googleVaughn, Samuel E.
dc.creator.googleFoley, Corinne
dc.creator.googleLu, Xiaoming
dc.creator.googlePatel, Zubin H.
dc.creator.googleZoller, Erin E.
dc.creator.googleMagnusen, Albert F.
dc.creator.googleWilliams, Adrienne H.
dc.creator.googleZiegler, Julie T.
dc.creator.googleComeau, Mary E.
dc.creator.googleMarion, Miranda C.
dc.creator.googleGlenn, Stuart B.
dc.creator.googleAdler, Adrienne H.
dc.creator.googleZiegler, Julie T.
dc.creator.googleComeau, Mary E.
dc.creator.googleMarion, Miranda C.
dc.creator.googleStuart B. Glenn
dc.creator.googleAdler, Adam
dc.creator.googleShen, Nan
dc.creator.googleNath, Swapan
dc.creator.googleStevens, Anne M.
dc.creator.googleFreedman, Barry I.
dc.creator.googleTsao, Betty P.
dc.creator.googleJacob, Chaim O.
dc.creator.googleKamen, Diane L.
dc.creator.googleBrown, Elizabeth E.
dc.creator.googleGilkeson, Gary S.
dc.creator.googleAlarcón, Graciela S.
dc.creator.googleReveille, John D.
dc.creator.googleAnaya, Juan-Manuel
dc.creator.googleJames, Judith A.
dc.creator.googleMoser, Kathy L.
dc.creator.googleCriswell, Lindsey A.
dc.creator.googleVilá, Luis M.
dc.creator.googleAlarcón-Riquelme, Marta E.
dc.creator.googlePetri, Michelle
dc.creator.googleScofield,R. Hal
dc.creator.googleKimberly, Robert P.
dc.creator.googleRamsey-Goldman, Rosalind
dc.creator.googleBinjoo, Young
dc.creator.googleChoi, Jeongim
dc.creator.googleBae, Sang-Cheol
dc.creator.googleBoackle, Susan A.
dc.creator.googleVyse, Timothy J.
dc.creator.googleGuthridge, Joel M.
dc.creator.googleNamjou, Bahram
dc.creator.googleGaffney, Patrick M.
dc.creator.googleLangefeld, Carl D.
dc.creator.googleKaufman, Kenneth M.
dc.creator.googleKelly, Jennifer A.
dc.creator.googleHarley, Isaac T. W.
dc.creator.googleHarley, John B.
dc.creator.googleKottyan, Leah C.
dc.identifier.doihttps://doi.org/10.3389/fgene.2014.00450
dc.relation.citationIssueNo. DEC
dc.relation.citationTitleFrontiers in Genetics
dc.relation.citationVolumeVol. 5


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