{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:14:57Z","timestamp":1792275297626,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T00:00:00Z","timestamp":1491436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31270930"],"award-info":[{"award-number":["31270930"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["U54\u2010AR\u2010057319 and R01\u2010AR\u2010047799"],"award-info":[{"award-number":["U54\u2010AR\u2010057319 and R01\u2010AR\u2010047799"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["U54\u2010RR\u2010019497"],"award-info":[{"award-number":["U54\u2010RR\u2010019497"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify risk alleles relevant to the causal and biologic mechanisms of antineutrophil cytoplasmic antibody (ANCA)\u2013associated vasculitis (AAV).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A genome\u2010wide association study and subsequent replication study were conducted in a total cohort of 1,986 cases of AAV (patients with granulomatosis with polyangiitis [Wegener's] [GPA] or microscopic polyangiitis [MPA]) and 4,723 healthy controls. Meta\u2010analysis of these data sets and functional annotation of identified risk loci were performed, and candidate disease variants with unknown functional effects were investigated for their impact on gene expression and\/or protein function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the genome\u2010wide significant associations identified, the largest effect on risk of AAV came from the single\u2010nucleotide polymorphism variants rs141530233 and rs1042169 at the\n                      <jats:italic>HLA\u2013DPB1<\/jats:italic>\n                      locus (odds ratio [OR] 2.99 and OR 2.82, respectively) which, together with a third variant, rs386699872, constitute a triallelic risk haplotype associated with reduced expression of the\n                      <jats:italic>HLA\u2013DPB1<\/jats:italic>\n                      gene and HLA\u2013DP protein in B cells and monocytes and with increased frequency of complementary proteinase 3 (PR3)\u2013reactive T cells relative to that in carriers of the protective haplotype. Significant associations were also observed at the\n                      <jats:italic>SERPINA1<\/jats:italic>\n                      and\n                      <jats:italic>PTPN22<\/jats:italic>\n                      loci, the peak signals arising from functionally relevant missense variants, and at\n                      <jats:italic>PRTN3<\/jats:italic>\n                      , in which the top\u2010scoring variant correlated with increased\n                      <jats:italic>PRTN3<\/jats:italic>\n                      expression in neutrophils. Effects of individual loci on AAV risk differed between patients with GPA and those with MPA or between patients with PR3\u2010ANCAs and those with myeloperoxidase\u2010ANCAs, but the collective population attributable fraction for these variants was substantive, at 77%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reveals the association of susceptibility to GPA and MPA with functional gene variants that explain much of the genetic etiology of AAV, could influence and possibly be predictors of the clinical presentation, and appear to alter immune cell proteins and responses likely to be key factors in the pathogenesis of AAV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.40034","type":"journal-article","created":{"date-parts":[[2016,12,28]],"date-time":"2016-12-28T11:52:52Z","timestamp":1482925972000},"page":"1054-1066","source":"Crossref","is-referenced-by-count":168,"title":["Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody\u2013Associated Vasculitis"],"prefix":"10.1002","volume":"69","author":[{"given":"Peter A.","family":"Merkel","sequence":"first","affiliation":[{"name":"University of Pennsylvania Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Xie","sequence":"additional","affiliation":[{"name":"Mount Sinai Hospital, Lunenfeld\u2010Tanenbaum Research Institute and Toronto General Research Institute Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Monach","sequence":"additional","affiliation":[{"name":"Boston University and VA Boston 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