{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:24:01Z","timestamp":1787063041060,"version":"build-2736575974"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["20522"],"award-info":[{"award-number":["20522"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2018,2]]},"abstract":"\n Objective<\/jats:title>\n \n Endoplasmic reticulum aminopeptidase 1 (\n ERAP<\/jats:styled-content>\n \u20101) and\n ERAP<\/jats:styled-content>\n \u20102\n ,<\/jats:italic>\n encoded on chromosome 5q15, trim endogenous peptides for\n HLA<\/jats:styled-content>\n \u2010mediated presentation to the immune system. Polymorphisms in\n \n ERAP<\/jats:styled-content>\n 1\n <\/jats:italic>\n and\/or\n \n ERAP<\/jats:styled-content>\n 2\n <\/jats:italic>\n are strongly associated with several immune\u2010mediated diseases with specific\n HLA<\/jats:styled-content>\n backgrounds, implicating altered peptide handling and presentation as prerequisites for autoreactivity against an arthritogenic peptide. Given the thorough characterization of disease risk\u2013associated polymorphisms that alter\n ERAP<\/jats:styled-content>\n activity, this study aimed instead to interrogate the expression effect of chromosome 5q15 polymorphisms to determine their effect on\n ERAP<\/jats:styled-content>\n isoform and protein expression.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n RNA<\/jats:styled-content>\n sequencing and genotyping across chromosome 5q15 were performed to detect genetic variants in\n \n ERAP<\/jats:styled-content>\n 1\n <\/jats:italic>\n and\n \n ERAP<\/jats:styled-content>\n 2\n <\/jats:italic>\n associated with altered total gene and isoform\u2010specific expression. The functional implication of a putative messenger\n RNA<\/jats:styled-content>\n splice\u2010altering variant on\n ERAP<\/jats:styled-content>\n \u20101 protein levels was validated using mass spectrometry.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Polymorphisms associated with ankylosing spondylitis (\n AS<\/jats:styled-content>\n ) significantly influenced the transcript and protein expression of ERAP\u20101 and ERAP\u20102. Disease risk\u2013associated polymorphisms in and around both genes were also associated with increased gene expression. Furthermore, key risk\u2010associated\n \n ERAP<\/jats:styled-content>\n 1\n <\/jats:italic>\n variants were associated with altered transcript splicing, leading to allele\u2010dependent alternate expression of 2 distinct isoforms and significant differences in the type of\n ERAP<\/jats:styled-content>\n \u20101 protein produced.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n In accordance with studies demonstrating that polymorphisms that increase aminopeptidase activity predispose to immune disease, the increased risk also attributed to increased expression of\n \n ERAP<\/jats:styled-content>\n 1\n <\/jats:italic>\n and\n \n ERAP<\/jats:styled-content>\n 2\n <\/jats:italic>\n supports the notion of using aminopeptidase inhibition to treat\n AS<\/jats:styled-content>\n and other\n ERAP<\/jats:styled-content>\n \u2010associated conditions.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.40369","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T12:46:42Z","timestamp":1509972402000},"page":"255-265","source":"Crossref","is-referenced-by-count":62,"title":["Genetic Variants in\n \n ERAP<\/scp>\n 1\n <\/i>\n and\n \n ERAP<\/scp>\n 2\n <\/i>\n Associated With Immune\u2010Mediated Diseases Influence Protein Expression and the Isoform Profile"],"prefix":"10.1002","volume":"70","author":[{"given":"Aimee L.","family":"Hanson","sequence":"first","affiliation":[{"name":"University of Queensland Princess Alexandra Hospital Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Cuddihy","sequence":"additional","affiliation":[{"name":"University of Queensland Princess Alexandra Hospital Brisbane Queensland 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