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dc.creatorNamjou, Bahram 
dc.creatorKim-Howard, Xana 
dc.creatorSun, Celi 
dc.creatorAdler, Adam 
dc.creatorChung, Sharon 
dc.creatorKaufman, Kenneth M. 
dc.creatorKelly, Jennifer A. 
dc.creatorGlenn, Stuart B. 
dc.creatorGuthridge, Joel M. 
dc.creatorScofield, Robert H. 
dc.creatorKimberly, Robert P. 
dc.creatorBrown, Elizabeth E. 
dc.creatorAlarcón, Graciela S. 
dc.creatorEdberg, Jeffrey C. 
dc.creatorKim, Jae-Hoon 
dc.creatorChoi, Jiyoung 
dc.creatorRamsey-Goldman, Rosalind 
dc.creatorPetri, Michelle A. 
dc.creatorReveille, John D. 
dc.creatorVilá, Luis M. 
dc.creatorBoackle, Susan 
dc.creatorFreedman, Barry I. 
dc.creatorTsao, Betty P. 
dc.creatorLangefeld, Carl D. 
dc.creatorVyse, Timothy J. 
dc.creatorJacob, Chaim O. 
dc.creatorPons-Estel, Bernardo A. 
dc.creatorNiewold, Timothy B. 
dc.creatorMoser Sivils, Kathy 
dc.creatorMerrill, Joan T. 
dc.creatorAnaya, Juan-Manuel 
dc.creatorGilkeson, Gary S. 
dc.creatorGaffney, Patrick M. 
dc.creatorBae, Sang-Cheol 
dc.creatorAlarcón-Riquelme, Marta E. 
dc.creatorHarley, John B. 
dc.creatorCriswell, Lindsey A. 
dc.creatorJames, Judith A. 
dc.creatorNath, Swapan K. 
dc.description.abstractProtein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical subphenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.761029, OR = 1.40 (95% CI = 1.25–1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67–0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG .20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.761025, OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs1217414 and rs3765598 may be associated with SLE. Further studies are required to confirm the involvement of rs2476601 with aCL IgG.
dc.format.mediumRecurso electrónico
dc.relation.ispartofPLoS ONE 8(8): e69404. doi:10.1371/journal.pone.0069404
dc.sourcereponame:Repositorio Institucional EdocUR
dc.sourceinstname:Universidad del Rosario
dc.titlePTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes
dc.audienceComunidad Rosarista
dc.publisherUniversidad del Rosario
dc.subject.keyword1Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America,
dc.subject.keyword2Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America,
dc.subject.keyword3Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
dc.subject.keyword4US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, United States of America,
dc.subject.keyword5Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America,
dc.subject.keyword6Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
dc.subject.keyword8Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
dc.subject.keyword9Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America,
dc.subject.keyword10Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America,
dc.subject.keyword11Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico,
dc.subject.decsLupus eritematoso sistémico
dc.rights.accesoAbierto (Texto completo)
dc.rights.licenciaEL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma.
dc.creator.googleNamjou, Bahram
dc.creator.googleKim-Howard, Xana
dc.creator.googleSun, Celi
dc.creator.googleAdler, Adam
dc.creator.googleChung, Sharon A.
dc.creator.googleKaufman, Kenneth M.
dc.creator.googleKelly, Jennifer A.
dc.creator.googleGlenn, Stuart B.
dc.creator.googleGuthridge, Joel M.
dc.creator.googleScofield, Robert H.
dc.creator.googleKimberly, Robert P.
dc.creator.googleBrown, Elizabeth E.
dc.creator.googleAlarcón, Graciela S.
dc.creator.googleEdberg, Jeffrey C.
dc.creator.googleKim, Jae-Hoon
dc.creator.googleChoi, Jiyoung
dc.creator.googleRamsey-Goldman, Rosalind
dc.creator.googlePetri, Michelle A.
dc.creator.googleReveille, John D.
dc.creator.googleVilá, Luis M.
dc.creator.googleBoackle, Susan A.
dc.creator.googleFreedman, Barry I.
dc.creator.googleTsao, Betty P.
dc.creator.googleLangefeld, Carl D.
dc.creator.googleVyse, Timothy J.
dc.creator.googleJacob, Chaim O.
dc.creator.googlePons-Estel, Bernardo
dc.creator.googleNiewold, Timothy B.
dc.creator.googleMoser Sivils, Kathy L.
dc.creator.googleMerrill, Joan T.
dc.creator.googleAnaya, Juan-Manuel
dc.creator.googleGilkeson, Gary S.
dc.creator.googleGaffney, Patrick M.
dc.creator.googleBae, Sang-Cheol
dc.creator.googleAlarcón-Riquelme, Marta E.
dc.creator.googleHarley, John B.
dc.creator.googleCriswell, Lindsey A.
dc.creator.googleJames, Judith A.
dc.creator.googleNath, Swapan K.

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