{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:52:09Z","timestamp":1761709929221,"version":"3.37.3"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773372","82073494","81573104"],"award-info":[{"award-number":["81773372","82073494","81573104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Graduate Innovation Experiment Center of Xi'an Jiaotong University","award":["YJSCX-2018-015"],"award-info":[{"award-number":["YJSCX-2018-015"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Bone Miner Metab"],"published-print":{"date-parts":[[2022,3]]},"DOI":"10.1007\/s00774-021-01287-2","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:04:01Z","timestamp":1642723441000},"page":"317-326","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An eQTL variant of ALDH1A2 is associated with Kashin-Beck disease in Chinese population"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5704-4341","authenticated-orcid":false,"given":"Di","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoli","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongqiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuena","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaofang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongmin","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"1287_CR1","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/s10067-012-2115-0","volume":"32","author":"Y Li","year":"2013","unstructured":"Li Y, Zhou Z, Shen B, Yang J, Kang P, Yang X, Liu G, Pei F (2013) Clinical features of Kashin-Beck disease in adults younger than 50 years; of age during a low incidence period: severe elbow and knee lesions. Clin Rheumatol 32:317\u2013324","journal-title":"Clin Rheumatol"},{"key":"1287_CR2","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1126\/science.324_1378","volume":"324","author":"S Richard","year":"2009","unstructured":"Richard S (2009) Diseases. A medical mystery in middle china. Science 324:1378\u20131381","journal-title":"Science"},{"key":"1287_CR3","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1007\/s10067-013-2267-6","volume":"32","author":"CX Cao","year":"2013","unstructured":"Cao CX, Zhang YG, Wu SX, Younas MI, Guo X (2013) Association of clinical features of bone and joint lesions between children and parents with Kashin\u2013Beck disease in Northwest China. Clin Rheumatol 32:1309\u20131316","journal-title":"Clin Rheumatol"},{"key":"1287_CR4","volume-title":"China statistical yearbook of health and family planning","author":"National Health and Family Planning Commission","year":"2018","unstructured":"National Health and Family Planning Commission (2018) China statistical yearbook of health and family planning. Pecking Union Medical College Press, Beijing"},{"key":"1287_CR5","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.joca.2007.09.002","volume":"16","author":"J Cao","year":"2008","unstructured":"Cao J, Li S, Shi Z, Yue Y, Sun J, Chen J, Fu Q, Hughes CE, Caterson B (2008) Articular cartilage metabolism in patients with Kashin-Beck disease: an endemic osteoarthropathy in China. Osteoarthritis Cartilage 16:680\u2013688","journal-title":"Osteoarthritis Cartilage"},{"key":"1287_CR6","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s12011-017-0988-0","volume":"180","author":"Y Guo","year":"2017","unstructured":"Guo Y, Li H, Yang L, Li Y, Wei B, Wang W, Gong H, Guo M, Nima C, Zhao S, Wang J (2017) Trace element levels in scalp hair of school children in Shigatse, Tibet, an endemic area for Kaschin-Beck disease (KBD). Bio Trace Elem Res 180:15\u201322","journal-title":"Bio Trace Elem Res"},{"key":"1287_CR7","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.envint.2016.12.006","volume":"99","author":"Z Shi","year":"2017","unstructured":"Shi Z, Pan P, Feng Y, Kan Z, Li Z, Wei F (2017) Environmental water chemistry and possible correlation with Kaschin-Beck disease (KBD) in northwestern Sichuan, China. Environ Int 99:282\u2013292","journal-title":"Environ Int"},{"key":"1287_CR8","first-page":"655","volume":"11","author":"B Zhang","year":"2010","unstructured":"Zhang B, Yang L, Wang W, Li Y, Li H (2010) Study on the selenium nutrition of children in Kaschin-Beck disease endemic areas in Rangtang county, Sichuan province. Chin Prev Med 11:655\u2013658","journal-title":"Chin Prev Med"},{"key":"1287_CR9","doi-asserted-by":"publisher","first-page":"a019133","DOI":"10.1101\/cshperspect.a019133","volume":"6","author":"E Li","year":"2014","unstructured":"Li E, Zhang Y (2014) DNA methylation in mammals. Cold Spring Harb Perspect Bio 6:a019133\u2013a019133","journal-title":"Cold Spring Harb Perspect Bio"},{"key":"1287_CR10","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1182\/blood-2013-03-487884","volume":"122","author":"MF Kaiser","year":"2013","unstructured":"Kaiser MF, Johnson DC, Wu P, Walker BA, Brioli A, Mirabella F, Wardell CP, Melchor L, Davies FE, Morgan GJ (2013) Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma. Blood 122:219\u2013226","journal-title":"Blood"},{"key":"1287_CR11","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13075-018-1531-1","volume":"20","author":"Y Wen","year":"2018","unstructured":"Wen Y, Li P, Hao J, Duan C, Han J, He A, Du Y, Liu L, Liang X, Zhang F, Guo X (2018) Integrating genome-wide DNA methylation and mRNA expression profiles identified different molecular features between Kashin-Beck disease and primary osteoarthritis. Arthritis Res Ther 20:41","journal-title":"Arthritis Res Ther"},{"key":"1287_CR12","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1016\/j.joca.2017.08.002","volume":"25","author":"W Wang","year":"2017","unstructured":"Wang W, Yu Y, Hao J, Wen Y, Han J, Hou W, Liu R, Zhao B, He A, Li P, Fan Q, Wu C, Wang S, Wang X, Ning Y, Guo X, Zhang F (2017) Genome-wide DNA methylation profiling of articular cartilage reveals significant epigenetic alterations in Kashin-Beck disease and osteoarthritis. Osteoarthritis Cartilage 25:2127\u20132133","journal-title":"Osteoarthritis Cartilage"},{"key":"1287_CR13","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.bone.2018.08.017","volume":"117","author":"L Han","year":"2018","unstructured":"Han L, Yang X, Sun W, Li Z, Ren H, Li B, Zhang R, Zhang D, Shi Z, Liu J, Cao J, Zhang J, Xiong Y (2018) The study of GPX3 methylation in patients with Kashin-Beck disease and its mechanism in chondrocyte apoptosis. Bone 117:15\u201322","journal-title":"Bone"},{"key":"1287_CR14","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/1440-1681.12522","volume":"43","author":"A Iorio","year":"2016","unstructured":"Iorio A, Velocci M, Graziano ME, Piacentini S, Polimanti R, Manfellotto D, Fuciarelli M (2016) Gpx1*pro198leu and gpx3 rs2070593 as genetic risk markers for Italian asthmatic patients. Clin Exp Pharmacol Physiol 43:277\u2013279","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"1287_CR15","doi-asserted-by":"publisher","first-page":"259","DOI":"10.3109\/03009740903270599","volume":"39","author":"X Shi","year":"2010","unstructured":"Shi X, Guo X, Lv A, Kang L, Zhou Y, Zhang Y, Wu XM, Bai YD (2010) Heritability estimates and linkage analysis of 23 short tandem repeat loci on chromosomes 2, 11, and 12 in an endemic osteochondropathy in china. Scand J Rheumatol 39:259\u2013265","journal-title":"Scand J Rheumatol"},{"key":"1287_CR16","doi-asserted-by":"publisher","first-page":"2033","DOI":"10.1016\/j.joca.2014.09.013","volume":"22","author":"LY Sun","year":"2014","unstructured":"Sun LY, Meng FG, Li Q, Zhao ZJ, He CZ, Wang SP, Sa RL, Man WW, Wang LH (2014) Effects of the consumption of rice from non-KBD areas and selenium supplementation on the prevention and treatment of paediatric Kaschin-Beck disease: an epidemiological intervention trial in the Qinghai Province. Osteoarthritis Cartilage 22:2033\u20132040","journal-title":"Osteoarthritis Cartilage"},{"key":"1287_CR17","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1017\/S0007114510002199","volume":"104","author":"W Sun","year":"2010","unstructured":"Sun W, Wang X, Zou X, Song R, Du X, Hu J, Xiong Y (2010) Selenoprotein P gene r25191g\/a polymorphism and quantification of selenoprotein P mRNA level in patients with Kashin-Beck disease. Br J Nutr 104:1283\u20131287","journal-title":"Br J Nutr"},{"key":"1287_CR18","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/ng.2957","volume":"46","author":"U Styrkarsdottir","year":"2014","unstructured":"Styrkarsdottir U, Thorleifsson G, Helgadottir HT, Bomer N, Metrustry S et al (2014) Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31. Nat Genet 46:498\u2013502","journal-title":"Nat Genet"},{"key":"1287_CR19","doi-asserted-by":"publisher","first-page":"7432","DOI":"10.1093\/hmg\/ddv433","volume":"24","author":"MD Rushton","year":"2015","unstructured":"Rushton MD, Reynard LN, Young DA, Shepherd C, Aubourg G, Gee F, Darlay R, Deehan D, Cordell HJ, Loughlin J (2015) Methylation quantitative trait locus (meqtl) analysis of osteoarthritis links epigenetics with genetic risk. Hum Mol Genet 24:7432\u20137444","journal-title":"Hum Mol Genet"},{"key":"1287_CR20","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.joca.2015.11.019","volume":"24","author":"U Aura","year":"2016","unstructured":"Aura U, Eiva B, Edvardas B, Sima G, Christian J (2016) Human articular chondrocytes with higher aldehyde dehydrogenase activity have stronger expression of COL2A1 and SOX9. Osteoarthritis Cartilage 24:873\u2013882","journal-title":"Osteoarthritis Cartilage"},{"key":"1287_CR21","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1302\/2046-3758.99.BJR-2019-0247.R1","volume":"9","author":"M Ma","year":"2020","unstructured":"Ma M, Liang X, Wang X, Zhang L, Wen Y (2020) The molecular mechanism study of COMP involved in the articular cartilage damage of Kashin-Beck disease. Bone Joint Res 9:578\u2013586","journal-title":"Bone Joint Res"},{"key":"1287_CR22","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s12881-017-0423-6","volume":"18","author":"Z Tai","year":"2017","unstructured":"Tai Z, Huang L, Lu F, Shi Y, Ma S, Cheng J, Lin H, Liu X, Li Y, Yang Z (2017) Association study of candidate genes for susceptibility to Kashin-Beck disease in a Tibetan population. BMC Med Genet 18:69","journal-title":"BMC Med Genet"},{"key":"1287_CR23","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.joca.2016.09.019","volume":"25","author":"C Wu","year":"2017","unstructured":"Wu C, Wen Y, Guo X, Yang T, Shen H, Chen X, Tian Q, Tan L, Deng HW, Zhang F (2017) Genetic association, mRNA and protein expression analysis identify ATG4C as a susceptibility gene for Kashin-Beck disease. Osteoarthritis Cartilage 25:281","journal-title":"Osteoarthritis Cartilage"},{"key":"1287_CR24","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1007\/s00198-015-3364-y","volume":"27","author":"Y Wen","year":"2016","unstructured":"Wen Y, Guo X, Hao J, Xiao X, Wang W, Wu C, Wang S, Yang T, Shen H, Chen X, Tan L, Tian Q, Deng HW, Zhang F (2016) Integrative analysis of genome-wide association studies and gene expression profiles identified candidate genes for osteoporosis in Kashin-Beck disease patients. Osteoporos Int 27:1041\u20131046","journal-title":"Osteoporos Int"},{"key":"1287_CR25","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1016\/j.joca.2017.01.003","volume":"25","author":"M Chu","year":"2017","unstructured":"Chu M, Zhu X, Wang C, Rong J, Wang Y, Wang S, Xing B, Tao Y, Zhuang X, Jiang L (2017) The rs4238326 polymorphism in ALDH1A2 gene potentially associated with non-post traumatic knee osteoarthritis susceptibility: a two-stage population-based study. Osteoarthritis Cartilage 25:1062\u20131067","journal-title":"Osteoarthritis Cartilage"},{"key":"1287_CR26","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1242\/dev.065938","volume":"139","author":"M Rhinn","year":"2012","unstructured":"Rhinn M, Dolle P (2012) Retinoic acid signaling during development. Development 139:843\u2013858","journal-title":"Development"},{"key":"1287_CR27","first-page":"221","volume":"1821","author":"LJ Gudas","year":"2012","unstructured":"Gudas LJ (2012) Emerging roles for retinoids in regeneration and differentiation in normal and disease states. Biochim Biophys Acta 1821:221","journal-title":"Biochim Biophys Acta"},{"key":"1287_CR28","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.ajhg.2011.09.015","volume":"89","author":"K Laue","year":"2011","unstructured":"Laue K, Pogoda HM, Daniel PB, Van Haeringen A, Alanay Y, Von Ameln S, Rachwalski M, Morgan T, Gray MJ, Breuning MH, Sawyer GM, Sutherland-Smith AJ, Nikkels PG, Kubisch C, Bloch W, Wollnik B, Hammerschmidt M, Robertson SP (2011) Craniosynostosis and multiple skeletal anomalies in humans and zebrafish result from a defect in the localized degradation of retinoic acid. Am J Hum Genet 89:595\u2013606","journal-title":"Am J Hum Genet"},{"key":"1287_CR29","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1002\/jez.b.21432","volume":"316","author":"HJ Kwon","year":"2011","unstructured":"Kwon HJ, Shin JO, Lee JM, Cho KW, Lee MJ, Cho SW, Jung HS (2011) Retinoic acid modulates chondrogenesis in the developing mouse cranial base. J Exp Zool B Mol Dev Evol 316:574\u2013583","journal-title":"J Exp Zool B Mol Dev Evol"},{"key":"1287_CR30","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1002\/jcp.21262","volume":"213","author":"SL Adams","year":"2007","unstructured":"Adams SL, Cohen AJ, Lassov\u00e1 L (2007) Integration of signaling pathways regulating chondrocyte differentiation during endochondral bone formation. J Cell Physiol 213:635\u2013641","journal-title":"J Cell Physiol"},{"key":"1287_CR31","doi-asserted-by":"publisher","first-page":"2514","DOI":"10.1210\/en.2002-220969","volume":"144","author":"X Li","year":"2003","unstructured":"Li X, Schwarz EM, Zuscik MJ, Rosier RN, Ionescu AM, Puzas JE, Drissi H, Sheu TJ, O\u2019Keefe RJ (2003) Retinoic acid stimulates chondrocyte differentiation and enhances bone morphogenetic protein effects through induction of Smad1 and smad5. Endocrinology 144:2514\u20132523","journal-title":"Endocrinology"},{"key":"1287_CR32","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1002\/art.40545","volume":"70","author":"C Shepherd","year":"2018","unstructured":"Shepherd C, Zhu D, Skelton AJ, Combe J, Threadgold H, Zhu L, Vincent TL, Stuart P, Reynard LN, Loughlin J (2018) Functional characterisation of the osteoarthritis genetic risk residing at ALDH1A2 identifies rs12915901 as a key target variant. Arthritis Rheumatol 70:1577\u20131587","journal-title":"Arthritis Rheumatol"},{"key":"1287_CR33","first-page":"1786","volume":"5","author":"JD Zhou","year":"2014","unstructured":"Zhou JD, Yao DM, Zhang YY, Ma JC, Wen XM, Yang J, Guo H, Chen Q, Lin J, Qian J (2014) Gpx3 hypermethylation serves as an independent prognostic biomarker in non-m3 acute myeloid leukemia. Am J Cancer Cancer Res 5:1786\u20131794","journal-title":"Am J Cancer Cancer Res"},{"key":"1287_CR34","doi-asserted-by":"publisher","first-page":"3408","DOI":"10.1002\/art.30526","volume":"63","author":"Y Shi","year":"2011","unstructured":"Shi Y, Lu F, Liu X, Wang Y, Yang Z (2011) Genetic variants in the HLA-DRB1 gene are associated with Kashin-Beck disease in the Tibetan population. Arthritis Rheum 63:3408\u20133416","journal-title":"Arthritis Rheum"},{"key":"1287_CR35","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1242\/dev.071688","volume":"139","author":"EW Kuijk","year":"2012","unstructured":"Kuijk EW, van Tol LT, Van de Velde H, Wubbolts R, Welling M, Geijsen N, Roelen BA (2012) The roles of Fgf and MAP kinase signaling in the segregation of the epiblast and hypoblast cell lineages in bovine and human embryos. Development 139:871\u2013882","journal-title":"Development"}],"container-title":["Journal of Bone and Mineral Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00774-021-01287-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00774-021-01287-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00774-021-01287-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T09:07:32Z","timestamp":1646816852000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00774-021-01287-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,21]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["1287"],"URL":"https:\/\/doi.org\/10.1007\/s00774-021-01287-2","relation":{},"ISSN":["0914-8779","1435-5604"],"issn-type":[{"type":"print","value":"0914-8779"},{"type":"electronic","value":"1435-5604"}],"subject":[],"published":{"date-parts":[[2022,1,21]]},"assertion":[{"value":"10 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that there are no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}