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dc.contributor.authorKanaan, S. B.en_US
dc.contributor.authorOnat, O. E.en_US
dc.contributor.authorBalandraud, N.en_US
dc.contributor.authorMartin, G. V.en_US
dc.contributor.authorNelson, J. L.en_US
dc.contributor.authorAzzouz, D. F.en_US
dc.contributor.authorAuger, I.en_US
dc.contributor.authorArnoux, F.en_US
dc.contributor.authorMartin, M.en_US
dc.contributor.authorRoudier, J.en_US
dc.contributor.authorOzcelik, T.en_US
dc.contributor.authorLambert, N. C.en_US
dc.date.accessioned2018-04-12T10:53:19Z
dc.date.available2018-04-12T10:53:19Z
dc.date.issued2016en_US
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11693/36786
dc.description.abstractBackground: Autoimmune diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc) are characterized by a strong genetic susceptibility from the Human Leucocyte Antigen (HLA) locus. Additionally, disorders of epigenetic processes, in particular non-random X chromosome inactivation (XCI), have been reported in many female-predominant autoimmune diseases. Here we test the hypothesis that women with RA or SSc who are strongly genetically predisposed are less susceptible to XCI bias. Methods: Using methylation sensitive genotyping of the androgen receptor (AR) gene, XCI profiles were performed in peripheral blood mononuclear cells from 161 women with RA, 96 women with SSc and 100 healthy women. HLA-DRB1 and DQB1 were genotyped. Presence of specific autoantibodies was documented for patients. XCI skewing was defined as having a ratio ≥ 80:20 of cells inactivating the same X chromosome. Results: 110 women with RA, 68 women with SSc, and 69 controls were informative for the AR polymorphism. Among them 40.9% of RA patients and 36.8% of SSc patients had skewed XCI compared to 17.4% of healthy women (P = 0.002 and 0.018, respectively). Presence of RA-susceptibility alleles coding for the "shared epitope" correlated with higher skewing among RA patients (P = 0.002) and such correlation was not observed in other women, healthy or with SSc. Presence of SSc-susceptibility alleles did not correlate with XCI patterns among SSc patients. Conclusion: Data demonstrate XCI skewing in both RA and SSc compared to healthy women. Unexpectedly, skewed XCI occurs more often in women with RA carrying the shared epitope, which usually reflects severe disease. This reinforces the view that loss of mosaicism in peripheral blood may be a consequence of chronic autoimmunity. © 2016 Kanaan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.language.isoEnglishen_US
dc.source.titlePLoS ONEen_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pone.0158550en_US
dc.subjectHLA DQB1 antigenen_US
dc.subjectHLA DRB1 antigenen_US
dc.subjectAndrogen receptoren_US
dc.subjectAutoantibodyen_US
dc.subjectHLA antigenen_US
dc.subjectHLA DQ antigenen_US
dc.subjectAutoimmunityen_US
dc.subjectChromosome mosaicismen_US
dc.subjectControlled studyen_US
dc.subjectGene locusen_US
dc.subjectGenetic susceptibilityen_US
dc.subjectDNA methylationen_US
dc.subjectGenetic epigenesisen_US
dc.subjectGenetic predispositionen_US
dc.subjectMononuclear cellen_US
dc.subjectRheumatoid arthritisen_US
dc.subjectSystemic sclerosisen_US
dc.subjectAutoantibodiesen_US
dc.subjectCase-Control Studiesen_US
dc.subjectDNA Methylationen_US
dc.subjectGenotypeen_US
dc.subjectHLA Antigensen_US
dc.subjectHLA-DQ beta-Chainsen_US
dc.subjectHLA-DRB1 Chainsen_US
dc.subjectHumansen_US
dc.subjectX Chromosome Inactivationen_US
dc.titleEvaluation of X chromosome inactivation with respect to HLA genetic susceptibility in rheumatoid arthritis and systemic sclerosisen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.citation.spage1en_US
dc.citation.epage12en_US
dc.citation.volumeNumber11en_US
dc.citation.issueNumber6en_US
dc.identifier.doi10.1371/journal.pone.0158550en_US
dc.publisherPublic Library of Scienceen_US


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