{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:44:15Z","timestamp":1790397855320,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,4,5]],"date-time":"2019-04-05T00:00:00Z","timestamp":1554422400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,4,5]],"date-time":"2019-04-05T00:00:00Z","timestamp":1554422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"CHU Sainte&amp;#x2010;Justine Foundation"},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"name":"La Fondation Yves Cotrel de l&amp;#x2019;Institut de France, Paris, France"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The cellular and molecular mechanisms underlying spinal deformity progression in adolescent idiopathic scoliosis (AIS) remain poorly understood. In this study, 804 French-Canadian patients and 278 age- and sex-matched controls were enrolled and genotyped for 12 single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 (<jats:italic>CHI3L1<\/jats:italic>) gene or its promoter. The plasma YKL-40 levels were determined by ELISA. We showed that elevation of circulating YKL-40 levels was correlated with a reduction of spinal deformity progression risk. We further identified significant associations of multiple <jats:italic>CHI3L1<\/jats:italic> SNPs and their haplotypes with plasma YKL-40 levels and scoliosis severity as a function of their classification in a specific endophenotype. In the endophenotype FG3 group, we found that patients harboring the haplotype G-G-A-G-G-A (rs880633|rs1538372|rs4950881|rs10399805|rs6691378|rs946261), which presented in 48% of the cases, showed a positive correlation with the plasma YKL-40 levels (<jats:italic>P<\/jats:italic>\u2009=\u20097.6\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup> and coefficient\u2009=\u200936). Conversely, the haplotype A-A-G-G-G-G, which presented in 15% of the analyzed subjects, showed a strong negative association with the plasma YKL-40 levels (<jats:italic>P<\/jats:italic>\u2009=\u20092\u2009\u00d7\u200910<jats:sup>\u22129<\/jats:sup> and coefficient\u2009=\u2009\u22129.56). We found that this haplotype showed the strongest association with AIS patients in endophenotype FG2 (<jats:italic>P<\/jats:italic>\u2009=\u20099.9\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup> and coefficient\u2009=\u2009\u221213.53), who more often develop severe scoliosis compared to those classified in the other two endophenotypes. Of note, it showed stronger association in females (<jats:italic>P<\/jats:italic>\u2009=\u20091.6\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup> and coefficient\u2009=\u2009\u221210.08) than males (<jats:italic>P<\/jats:italic>\u2009=\u20090.0021 and coefficient\u2009=\u2009\u22129.01). At the functional level, we showed that YKL-40 treatments rescued Gi-coupled receptor signalling dysfunction occurring in primary AIS osteoblasts. Collectively, our findings reveal a novel role for YKL-40 in AIS pathogenesis and a new molecular mechanism interfering with spinal deformity progression.<\/jats:p>","DOI":"10.1038\/s41598-019-41191-4","type":"journal-article","created":{"date-parts":[[2019,4,5]],"date-time":"2019-04-05T10:02:56Z","timestamp":1554458576000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Association of Circulating YKL-40 Levels and CHI3L1 Variants with the Risk of Spinal Deformity Progression in Adolescent Idiopathic Scoliosis"],"prefix":"10.1038","volume":"9","author":[{"given":"Dina","family":"Nada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Julien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre H.","family":"Rompr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Yvonne","family":"Akoume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen F.","family":"Gorman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Samuels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Kost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9214-4487","authenticated-orcid":false,"given":"Dawei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Moreau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,5]]},"reference":[{"key":"41191_CR1","first-page":"1","volume":"1","author":"JC Cheng","year":"2015","unstructured":"Cheng, J. 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The authors declare no other potential conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"5712"}}