{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:32:00Z","timestamp":1788337920624,"version":"build-2803163510"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,4,7]],"date-time":"2017-04-07T00:00:00Z","timestamp":1491523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,4,7]],"date-time":"2017-04-07T00:00:00Z","timestamp":1491523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Beh\u00e7et\u2019s disease (BD) is reportedly associated with polymorphisms of the ubiquitin-associated domain containing 2 (<jats:italic>UBAC2<\/jats:italic>) gene in Turkish, Italian, and Chinese populations. Here we investigated whether <jats:italic>UBAC2<\/jats:italic> polymorphisms were associated with BD in a Japanese population. Using data from 611 Japanese BD patients and 737 Japanese controls who participated in our previous genome-wide association study, we analyzed the 58 genotyped single-nucleotide polymorphisms (SNPs) in the region 100\u2009kb upstream and downstream of <jats:italic>UBAC2<\/jats:italic>. We also performed imputation analysis in the region, with 562 imputed SNPs included in the statistical analyses. Association testing revealed that the T allele of rs9517723 in the lncRNA <jats:italic>LOC107984558<\/jats:italic> was significantly associated with ocular and central nervous system (CNS) lesions and showed the strongest association under the recessive model (TT vs. CT+CC: ocular lesion, <jats:italic>P<\/jats:italic>c\u2009=\u20090.0099, OR\u2009=\u20091.56; CNS lesion, <jats:italic>P<\/jats:italic>c\u2009=\u20090.0052, OR\u2009=\u20093.42). Expression analysis revealed that rs9517723 TT homozygotes showed significantly increased <jats:italic>UBAC2<\/jats:italic> expression (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Our findings suggest that enhanced <jats:italic>UBAC2<\/jats:italic> expression associated with the homozygous risk allele (TT) of rs9517723 could induce overactivation of ubiquitination-related pathway, resulting in the development of ocular and CNS lesions in BD.<\/jats:p>","DOI":"10.1038\/s41598-017-00877-3","type":"journal-article","created":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T19:50:11Z","timestamp":1491249011000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Comprehensive analysis of the association between UBAC2 polymorphisms and Beh\u00e7et\u2019s disease in a Japanese population"],"prefix":"10.1038","volume":"7","author":[{"given":"Kyoko","family":"Yamazoe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Meguro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuko","family":"Shibuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhisa","family":"Mizuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,7]]},"reference":[{"key":"877_CR1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/S0049-0172(98)80001-2","volume":"27","author":"VG Kaklamani","year":"1998","unstructured":"Kaklamani, V. G., Vaiopoulos, G. & Kaklamanis, P. G. Beh\u00e7et\u2019s disease. Semin. Arthritis Rheum. \n                           27, 197\u2013217 (1998).","journal-title":"Semin. Arthritis Rheum."},{"key":"877_CR2","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1001\/archopht.1982.01030040433013","volume":"100","author":"S Ohno","year":"1982","unstructured":"Ohno, S. et al. Close association of HLA-Bw51 with Beh\u00e7et\u2019s disease. Arch. Opthalmol. \n                           100, 1455\u20131458 (1982).","journal-title":"Arch. Opthalmol."},{"key":"877_CR3","first-page":"1921","volume":"40","author":"K Yabuki","year":"1999","unstructured":"Yabuki, K. et al. Association of MICA gene and HLA-B*5101 with Beh\u00e7et\u2019s disease in Greece. Invest. Ophthalmol. Vis. Sci. \n                           40, 1921\u20131926 (1999).","journal-title":"Invest. Ophthalmol. Vis. 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Arthritis Rheum. \n                           42, 1961\u20131966 (1999).","journal-title":"Arthritis Rheum."},{"key":"877_CR6","doi-asserted-by":"publisher","first-page":"R66","DOI":"10.1186\/ar2695","volume":"11","author":"Y Fei","year":"2009","unstructured":"Fei, Y. et al. Identification of novel genetic susceptibility loci for Beh\u00e7et\u2019s disease using a genome-wide association study. Arthritis Res. Ther. \n                           11, R66 (2009).","journal-title":"Arthritis Res. Ther."},{"key":"877_CR7","doi-asserted-by":"publisher","first-page":"3607","DOI":"10.1002\/art.30604","volume":"63","author":"AH Sawalha","year":"2011","unstructured":"Sawalha, A. H. et al. A putative functional variant within the UBAC2 gene is associated with increased risk of Beh\u00e7et\u2019s disease. Arthritis Rheum. \n                           63, 3607\u20133612 (2011).","journal-title":"Arthritis Rheum."},{"key":"877_CR8","doi-asserted-by":"publisher","first-page":"R70","DOI":"10.1186\/ar3789","volume":"14","author":"S Hou","year":"2012","unstructured":"Hou, S. et al. Replication study confirms the association between UBAC2 and Beh\u00e7et\u2019s disease in two independent Chinese sets of patients and controls. Arthritis Res. Ther. \n                           14, R70 (2012).","journal-title":"Arthritis Res. Ther."},{"key":"877_CR9","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/nrg2521","volume":"10","author":"TR Mercer","year":"2009","unstructured":"Mercer, T. R., Dinger, M. E. & Mattick, J. S. Long non-coding RNAs: insights into functions. Nat. Rev. Genet. \n                           10, 155\u2013159 (2009).","journal-title":"Nat. Rev. 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Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Beh\u00e7et\u2019s disease. Nat. Genet. \n                           42, 698\u2013702 (2010).","journal-title":"Nat. Genet."},{"key":"877_CR15","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1158\/2159-8290.CD-11-0209","volume":"1","author":"JR Prensner","year":"2011","unstructured":"Prensner, J. R. & Chinnaiyan, A. M. The emergence of lncRNAs in cancer biology. Cancer Discov. \n                           1, 391\u2013407 (2011).","journal-title":"Cancer Discov."},{"key":"877_CR16","doi-asserted-by":"publisher","unstructured":"Jain, S., Thakkar, N., Chhatai, J., Bhadra, M. P. & Bhadra, U. Long non-coding RNA: Functional agent for disease traits. 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An insertion\/deletion polymorphism within RERT-lncRNA modulates hepatocellular carcinoma risk. Cancer Res. \n                           72, 6163\u20136172 (2012).","journal-title":"Cancer Res."},{"key":"877_CR22","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1111\/j.1349-7006.2010.01737.x","volume":"102","author":"S Chung","year":"2011","unstructured":"Chung, S. et al. Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility. Cancer Sci. \n                           102, 245\u2013252 (2011).","journal-title":"Cancer Sci."},{"key":"877_CR23","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1101\/gr.4200206","volume":"16","author":"T Ravasi","year":"2006","unstructured":"Ravasi, T. et al. Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome. 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LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics. \n                           26, 2336\u20132337 (2010).","journal-title":"Bioinformatics."},{"key":"877_CR32","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. \n                           81, 559\u2013575 (2007).","journal-title":"Am. J. Hum. Genet."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00877-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00877-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00877-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T03:36:48Z","timestamp":1671766608000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-00877-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,7]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["877"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-00877-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,7]]},"assertion":[{"value":"4 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"742"}}