{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:05:45Z","timestamp":1792098345815,"version":"4.4.0"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,12,27]],"date-time":"2014-12-27T00:00:00Z","timestamp":1419638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Natural Scientific Fund of China","award":["81102086"],"award-info":[{"award-number":["81102086"]}]},{"name":"Science and Technology Research and Development Program of in Shaanxi Province of China","award":["2013KJXX-51"],"award-info":[{"award-number":["2013KJXX-51"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Kashin\u2010Beck disease (KBD) is a chronic osteochondropathy, the pathogenesis of which remains elusive. The aim of this study was to identify susceptibility genes for KBD by conducting a 2\u2010stage genome\u2010wide association study (GWAS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ninety patients with grade II or grade III KBD with extreme KBD phenotypes and 1,627 healthy control subjects were enrolled in the initial GWAS. Affymetrix Genome\u2010Wide Human SNP Array 6.0 was used for genotyping. For the replication study, 9 single\u2010nucleotide polymorphisms (SNPs) of the significant gene identified by the GWAS (<jats:italic>ITPR2<\/jats:italic>) were tested in an independent validation sample composed of 559 patients with KBD and 467 healthy control subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The GWAS identified significant association (<jats:italic>P<\/jats:italic> = 1.58 \u00d7 10<jats:sup>\u22128<\/jats:sup>) between KBD and a novel locus, <jats:italic>ITPR2<\/jats:italic> SNP rs10842750. The replication study showed significant associations with KBD at 9 <jats:italic>ITPR2<\/jats:italic> SNPs, including rs10842750 (<jats:italic>P<\/jats:italic> = 5.97 \u00d7 10<jats:sup>\u22123<\/jats:sup>), rs16931011 (<jats:italic>P<\/jats:italic> = 1.29 \u00d7 10<jats:sup>\u22123<\/jats:sup>), rs1531928 (<jats:italic>P<\/jats:italic> = 4.95 \u00d7 10<jats:sup>\u22123<\/jats:sup>), rs4414322 (<jats:italic>P<\/jats:italic> = 4.40 \u00d7 10<jats:sup>\u22123<\/jats:sup>), rs11048570 (<jats:italic>P<\/jats:italic> = 4.53 \u00d7 10<jats:sup>\u22123<\/jats:sup>), rs11048572 (<jats:italic>P<\/jats:italic> = 4.43 \u00d7 10<jats:sup>\u22123<\/jats:sup>), rs2017510 (<jats:italic>P<\/jats:italic> = 4.58 \u00d7 10<jats:sup>\u22123<\/jats:sup>), rs9669395 (<jats:italic>P<\/jats:italic> = 5.77 \u00d7 10<jats:sup>\u22123<\/jats:sup>), and rs1002835 (<jats:italic>P<\/jats:italic> = 4.85 \u00d7 10<jats:sup>\u22123<\/jats:sup>). In patients with KBD, the genotype score for rs10842750 was also correlated with KBD clinical severity grades (<jats:italic>P<\/jats:italic> = 0.013).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results strongly suggest that <jats:italic>ITPR2<\/jats:italic> is a novel susceptibility gene for KBD in Han Chinese. This study may provide new insights into the pathogenesis and rationale for treatment of KBD as well as other osteoarthritides with similar articular cartilage lesions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38898","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T11:19:24Z","timestamp":1412853564000},"page":"176-181","source":"Crossref","is-referenced-by-count":28,"title":["Brief Report: Genome\u2010Wide Association Study Identifies <i>ITPR2<\/i> as a Susceptibility Gene for Kashin\u2010Beck Disease in Han Chinese"],"prefix":"10.1002","volume":"67","author":[{"given":"Feng","family":"Zhang","sequence":"first","affiliation":[{"name":"Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wen","sequence":"additional","affiliation":[{"name":"Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Guo","sequence":"additional","affiliation":[{"name":"Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingang","family":"Zhang","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital and Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tielin","family":"Yang","sequence":"additional","affiliation":[{"name":"Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Shen","sequence":"additional","affiliation":[{"name":"Tulane University New Orleans Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangding","family":"Chen","sequence":"additional","affiliation":[{"name":"Hunan Normal University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Tian","sequence":"additional","affiliation":[{"name":"Tulane University New Orleans Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Wen","family":"Deng","sequence":"additional","affiliation":[{"name":"Tulane University New Orleans Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.09.015"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30526"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.134155"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.176"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27184"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.08.001"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119899109"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60681-3"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-1612"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70222-3"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.22.6349"},{"key":"e_1_2_6_13_1","first-page":"615","article-title":"Chondrocyte apoptosis and expression of Bcl\u20102, Bax, Fas, and iNOS in articular cartilage in patients with Kashin\u2010Beck disease","volume":"33","author":"Wang SJ","year":"2006","journal-title":"J Rheumatol"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.3.3.705"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.11.3078"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711324105"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1063"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.07.003"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/491658"}],"container-title":["Arthritis &amp; 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