Association of Circulating YKL-40 Levels and CHI3L1 Variants with the Risk of Spinal Deformity Progression in Adolescent Idiopathic Scoliosis. View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Dina Nada, Cédric Julien, Pierre H Rompré, Marie-Yvonne Akoume, Kristen F Gorman, Mark E Samuels, Emile Levy, Jason Kost, Dawei Li, Alain Moreau

ABSTRACT

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 (CHI3L1) 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 CHI3L1 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 (P = 7.6 × 10-6 and coefficient = 36). 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 (P = 2 × 10-9 and coefficient = -9.56). We found that this haplotype showed the strongest association with AIS patients in endophenotype FG2 (P = 9.9 × 10-6 and coefficient = -13.53), who more often develop severe scoliosis compared to those classified in the other two endophenotypes. Of note, it showed stronger association in females (P = 1.6 × 10-7 and coefficient = -10.08) than males (P = 0.0021 and coefficient = -9.01). 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. More... »

PAGES

5712

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-41191-4

DOI

http://dx.doi.org/10.1038/s41598-019-41191-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113261531

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30952886


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Clinical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of Montreal", 
          "id": "https://www.grid.ac/institutes/grid.14848.31", 
          "name": [
            "Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital, Research Center, Montreal, QC, Canada.", 
            "Program of Biomedical Sciences, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC, Canada."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Nada", 
        "givenName": "Dina", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital, Research Center, Montreal, QC, Canada."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Julien", 
        "givenName": "C\u00e9dric", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Montreal", 
          "id": "https://www.grid.ac/institutes/grid.14848.31", 
          "name": [
            "Faculty of Dentistry, Universit\u00e9 de Montr\u00e9al, Montreal, QC, Canada."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rompr\u00e9", 
        "givenName": "Pierre H", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital, Research Center, Montreal, QC, Canada."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Akoume", 
        "givenName": "Marie-Yvonne", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "California State University, Chico", 
          "id": "https://www.grid.ac/institutes/grid.253555.1", 
          "name": [
            "Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital, Research Center, Montreal, QC, Canada.", 
            "Department of Biological Sciences, California State University, Chico, CA, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gorman", 
        "givenName": "Kristen F", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Montreal", 
          "id": "https://www.grid.ac/institutes/grid.14848.31", 
          "name": [
            "Sainte-Justine University Hospital Research Center, Montreal, QC, Canada.", 
            "Department of Medicine, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC, Canada."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Samuels", 
        "givenName": "Mark E", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Montreal", 
          "id": "https://www.grid.ac/institutes/grid.14848.31", 
          "name": [
            "Sainte-Justine University Hospital Research Center, Montreal, QC, Canada.", 
            "Department of Nutrition, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC, Canada."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Levy", 
        "givenName": "Emile", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Vermont", 
          "id": "https://www.grid.ac/institutes/grid.59062.38", 
          "name": [
            "Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kost", 
        "givenName": "Jason", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Vermont", 
          "id": "https://www.grid.ac/institutes/grid.59062.38", 
          "name": [
            "Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA.", 
            "Neuroscience, Behavior, and Health Initiative, University of Vermont, Burlington, Vermont, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Li", 
        "givenName": "Dawei", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Montreal", 
          "id": "https://www.grid.ac/institutes/grid.14848.31", 
          "name": [
            "Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital, Research Center, Montreal, QC, Canada. alain.moreau@recherche-ste-justine.qc.ca.", 
            "Program of Biomedical Sciences, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC, Canada. alain.moreau@recherche-ste-justine.qc.ca.", 
            "Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC, Canada. alain.moreau@recherche-ste-justine.qc.ca.", 
            "Department of Stomatology, Faculty of Dentistry, Universit\u00e9 de Montr\u00e9al, Montreal, QC, Canada. alain.moreau@recherche-ste-justine.qc.ca."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Moreau", 
        "givenName": "Alain", 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1002/jbmr.2281", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001680042"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/147323000903700102", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005458972"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/147323000903700102", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005458972"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa0708801", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005744340"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/brs.0000000000000807", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005844942"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/brs.0000000000000807", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005844942"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.neubiorev.2008.01.005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006348241"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13013-015-0054-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007831386", 
          "https://doi.org/10.1186/s13013-015-0054-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/bioinformatics/bth457", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008081196"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/brs.0b013e3181cf39ff", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008278255"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/brs.0b013e3181cf39ff", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008278255"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1080/10408363.2016.1190683", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009242622"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1748-7161-1-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014534758", 
          "https://doi.org/10.1186/1748-7161-1-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1086/519795", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019061180"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00586-012-2389-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019588452", 
          "https://doi.org/10.1007/s00586-012-2389-6"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00586-011-2074-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021405387", 
          "https://doi.org/10.1007/s00586-011-2074-1"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1748-7161-9-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025686134", 
          "https://doi.org/10.1186/1748-7161-9-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.regpep.2013.03.022", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026622117"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1159/000119108", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027216506"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3109/09513590.2013.879854", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031820213"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jor.22090", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032002643"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2217/pme.12.117", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034537175"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cyto.2010.12.018", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035076861"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.spinee.2015.03.014", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039448331"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.spinee.2015.03.014", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039448331"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00007632-200204010-00010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040515546"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00007632-200204010-00010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040515546"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/blo.0b013e31811f39fa", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042945813"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/blo.0b013e31811f39fa", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042945813"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/ar3391", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051225804", 
          "https://doi.org/10.1186/ar3391"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1750-1326-6-31", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052296288", 
          "https://doi.org/10.1186/1750-1326-6-31"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2217/fon.09.66", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053579381"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.152.3723.711", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062488495"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1176/appi.ajp.160.4.636", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063495220"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1077319278", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1155/2018/9784083", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1105625537"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2019-12", 
    "datePublishedReg": "2019-12-01", 
    "description": "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 (CHI3L1) 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 CHI3L1 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 (P\u2009=\u20097.6\u2009\u00d7\u200910-6 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 (P\u2009=\u20092\u2009\u00d7\u200910-9 and coefficient\u2009=\u2009-9.56). We found that this haplotype showed the strongest association with AIS patients in endophenotype FG2 (P\u2009=\u20099.9\u2009\u00d7\u200910-6 and coefficient\u2009=\u2009-13.53), who more often develop severe scoliosis compared to those classified in the other two endophenotypes. Of note, it showed stronger association in females (P\u2009=\u20091.6\u2009\u00d7\u200910-7 and coefficient\u2009=\u2009-10.08) than males (P\u2009=\u20090.0021 and coefficient\u2009=\u2009-9.01). 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.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/s41598-019-41191-4", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1045337", 
        "issn": [
          "2045-2322"
        ], 
        "name": "Scientific Reports", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "9"
      }
    ], 
    "name": "Association of Circulating YKL-40 Levels and CHI3L1 Variants with the Risk of Spinal Deformity Progression in Adolescent Idiopathic Scoliosis.", 
    "pagination": "5712", 
    "productId": [
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41598-019-41191-4"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1113261531"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101563288"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30952886"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41598-019-41191-4", 
      "https://app.dimensions.ai/details/publication/pub.1113261531"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-16T06:23", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000377_0000000377/records_106822_00000003.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://www.nature.com/articles/s41598-019-41191-4"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-41191-4'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-41191-4'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-41191-4'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-019-41191-4'


 

This table displays all metadata directly associated to this object as RDF triples.

234 TRIPLES      21 PREDICATES      58 URIs      20 LITERALS      8 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41598-019-41191-4 schema:about anzsrc-for:11
2 anzsrc-for:1103
3 schema:author N6e4cc3fa095e4cebb58027f254c2fd1f
4 schema:citation sg:pub.10.1007/s00586-011-2074-1
5 sg:pub.10.1007/s00586-012-2389-6
6 sg:pub.10.1186/1748-7161-1-2
7 sg:pub.10.1186/1748-7161-9-7
8 sg:pub.10.1186/1750-1326-6-31
9 sg:pub.10.1186/ar3391
10 sg:pub.10.1186/s13013-015-0054-7
11 https://app.dimensions.ai/details/publication/pub.1077319278
12 https://doi.org/10.1002/jbmr.2281
13 https://doi.org/10.1002/jor.22090
14 https://doi.org/10.1016/j.cyto.2010.12.018
15 https://doi.org/10.1016/j.neubiorev.2008.01.005
16 https://doi.org/10.1016/j.regpep.2013.03.022
17 https://doi.org/10.1016/j.spinee.2015.03.014
18 https://doi.org/10.1056/nejmoa0708801
19 https://doi.org/10.1080/10408363.2016.1190683
20 https://doi.org/10.1086/519795
21 https://doi.org/10.1093/bioinformatics/bth457
22 https://doi.org/10.1097/00007632-200204010-00010
23 https://doi.org/10.1097/blo.0b013e31811f39fa
24 https://doi.org/10.1097/brs.0000000000000807
25 https://doi.org/10.1097/brs.0b013e3181cf39ff
26 https://doi.org/10.1126/science.152.3723.711
27 https://doi.org/10.1155/2018/9784083
28 https://doi.org/10.1159/000119108
29 https://doi.org/10.1176/appi.ajp.160.4.636
30 https://doi.org/10.1177/147323000903700102
31 https://doi.org/10.2217/fon.09.66
32 https://doi.org/10.2217/pme.12.117
33 https://doi.org/10.3109/09513590.2013.879854
34 schema:datePublished 2019-12
35 schema:datePublishedReg 2019-12-01
36 schema:description 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 (CHI3L1) 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 CHI3L1 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 (P = 7.6 × 10<sup>-6</sup> and coefficient = 36). 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 (P = 2 × 10<sup>-9</sup> and coefficient = -9.56). We found that this haplotype showed the strongest association with AIS patients in endophenotype FG2 (P = 9.9 × 10<sup>-6</sup> and coefficient = -13.53), who more often develop severe scoliosis compared to those classified in the other two endophenotypes. Of note, it showed stronger association in females (P = 1.6 × 10<sup>-7</sup> and coefficient = -10.08) than males (P = 0.0021 and coefficient = -9.01). 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.
37 schema:genre research_article
38 schema:inLanguage en
39 schema:isAccessibleForFree true
40 schema:isPartOf N6a18563372c444e2a50d871277a385d0
41 Ne731d78766f34dd88c465c95dde98bb5
42 sg:journal.1045337
43 schema:name Association of Circulating YKL-40 Levels and CHI3L1 Variants with the Risk of Spinal Deformity Progression in Adolescent Idiopathic Scoliosis.
44 schema:pagination 5712
45 schema:productId N249119515cb245d185e2427509917e10
46 Na8325f5735c24a1cb9b3d63f2ac26cf9
47 Ne301a52e7890424fb0cccc953dc7da02
48 Ne900082a0f0441738f259949d9dca444
49 schema:sameAs https://app.dimensions.ai/details/publication/pub.1113261531
50 https://doi.org/10.1038/s41598-019-41191-4
51 schema:sdDatePublished 2019-04-16T06:23
52 schema:sdLicense https://scigraph.springernature.com/explorer/license/
53 schema:sdPublisher N4d491b7a501941bc8ef1e8627442d9e7
54 schema:url http://www.nature.com/articles/s41598-019-41191-4
55 sgo:license sg:explorer/license/
56 sgo:sdDataset articles
57 rdf:type schema:ScholarlyArticle
58 N06e9e0004f1c4a848a9cdd4e1ed8942a rdf:first N33f9fa1580274c1a872660297d3c421d
59 rdf:rest Nd70ed76a700449f485266e3048554fbf
60 N1b68fb099e98486793e502a97f496062 schema:affiliation https://www.grid.ac/institutes/grid.14848.31
61 schema:familyName Levy
62 schema:givenName Emile
63 rdf:type schema:Person
64 N1d839f57386347c09b0d8c4a035f337b rdf:first N356e671791584a48a578363c77d70cac
65 rdf:rest Nfd3cdea08658408a8d845c977c824386
66 N249119515cb245d185e2427509917e10 schema:name doi
67 schema:value 10.1038/s41598-019-41191-4
68 rdf:type schema:PropertyValue
69 N270084d078e8424f9ee92d3ba8a7cc01 schema:affiliation https://www.grid.ac/institutes/grid.14848.31
70 schema:familyName Samuels
71 schema:givenName Mark E
72 rdf:type schema:Person
73 N282f6fb208454c06813dc6868eed452f schema:affiliation https://www.grid.ac/institutes/grid.253555.1
74 schema:familyName Gorman
75 schema:givenName Kristen F
76 rdf:type schema:Person
77 N2a14cddc51e24cebb8d75b1f94d7d9ee schema:affiliation https://www.grid.ac/institutes/grid.59062.38
78 schema:familyName Kost
79 schema:givenName Jason
80 rdf:type schema:Person
81 N33f9fa1580274c1a872660297d3c421d schema:affiliation https://www.grid.ac/institutes/grid.59062.38
82 schema:familyName Li
83 schema:givenName Dawei
84 rdf:type schema:Person
85 N356e671791584a48a578363c77d70cac schema:affiliation N435dde9bed7942b7bb70eb6faf6812e1
86 schema:familyName Akoume
87 schema:givenName Marie-Yvonne
88 rdf:type schema:Person
89 N38d0f0b973494df0933183a21347bc70 schema:affiliation https://www.grid.ac/institutes/grid.14848.31
90 schema:familyName Nada
91 schema:givenName Dina
92 rdf:type schema:Person
93 N3b932bcaa18f46ec909180376dd86f07 rdf:first Nc16908354622434c9145c78a7e41dd8e
94 rdf:rest Na312416716e24fd1925d2680dd280cf4
95 N435dde9bed7942b7bb70eb6faf6812e1 schema:name Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital, Research Center, Montreal, QC, Canada.
96 rdf:type schema:Organization
97 N4d491b7a501941bc8ef1e8627442d9e7 schema:name Springer Nature - SN SciGraph project
98 rdf:type schema:Organization
99 N544fc566ff47487d909172baa357c914 schema:affiliation https://www.grid.ac/institutes/grid.14848.31
100 schema:familyName Moreau
101 schema:givenName Alain
102 rdf:type schema:Person
103 N6a18563372c444e2a50d871277a385d0 schema:volumeNumber 9
104 rdf:type schema:PublicationVolume
105 N6e4cc3fa095e4cebb58027f254c2fd1f rdf:first N38d0f0b973494df0933183a21347bc70
106 rdf:rest N3b932bcaa18f46ec909180376dd86f07
107 N6e631e1d26034e719302bdbeb3e17982 schema:affiliation https://www.grid.ac/institutes/grid.14848.31
108 schema:familyName Rompré
109 schema:givenName Pierre H
110 rdf:type schema:Person
111 Na312416716e24fd1925d2680dd280cf4 rdf:first N6e631e1d26034e719302bdbeb3e17982
112 rdf:rest N1d839f57386347c09b0d8c4a035f337b
113 Na8325f5735c24a1cb9b3d63f2ac26cf9 schema:name nlm_unique_id
114 schema:value 101563288
115 rdf:type schema:PropertyValue
116 Nc16908354622434c9145c78a7e41dd8e schema:affiliation Ne42525517cd34c0b9850c4cab0d70e52
117 schema:familyName Julien
118 schema:givenName Cédric
119 rdf:type schema:Person
120 Nc1e09b2901f64219becd1e8639a41798 rdf:first N2a14cddc51e24cebb8d75b1f94d7d9ee
121 rdf:rest N06e9e0004f1c4a848a9cdd4e1ed8942a
122 Nd70ed76a700449f485266e3048554fbf rdf:first N544fc566ff47487d909172baa357c914
123 rdf:rest rdf:nil
124 Ne301a52e7890424fb0cccc953dc7da02 schema:name pubmed_id
125 schema:value 30952886
126 rdf:type schema:PropertyValue
127 Ne42525517cd34c0b9850c4cab0d70e52 schema:name Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital, Research Center, Montreal, QC, Canada.
128 rdf:type schema:Organization
129 Ne731d78766f34dd88c465c95dde98bb5 schema:issueNumber 1
130 rdf:type schema:PublicationIssue
131 Ne900082a0f0441738f259949d9dca444 schema:name dimensions_id
132 schema:value pub.1113261531
133 rdf:type schema:PropertyValue
134 Nee0d9b271e0c4b2dbbe6dd18af550bde rdf:first N270084d078e8424f9ee92d3ba8a7cc01
135 rdf:rest Nef75971c242f489aa70a7056733d12b9
136 Nef75971c242f489aa70a7056733d12b9 rdf:first N1b68fb099e98486793e502a97f496062
137 rdf:rest Nc1e09b2901f64219becd1e8639a41798
138 Nfd3cdea08658408a8d845c977c824386 rdf:first N282f6fb208454c06813dc6868eed452f
139 rdf:rest Nee0d9b271e0c4b2dbbe6dd18af550bde
140 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
141 schema:name Medical and Health Sciences
142 rdf:type schema:DefinedTerm
143 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
144 schema:name Clinical Sciences
145 rdf:type schema:DefinedTerm
146 sg:journal.1045337 schema:issn 2045-2322
147 schema:name Scientific Reports
148 rdf:type schema:Periodical
149 sg:pub.10.1007/s00586-011-2074-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021405387
150 https://doi.org/10.1007/s00586-011-2074-1
151 rdf:type schema:CreativeWork
152 sg:pub.10.1007/s00586-012-2389-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019588452
153 https://doi.org/10.1007/s00586-012-2389-6
154 rdf:type schema:CreativeWork
155 sg:pub.10.1186/1748-7161-1-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014534758
156 https://doi.org/10.1186/1748-7161-1-2
157 rdf:type schema:CreativeWork
158 sg:pub.10.1186/1748-7161-9-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025686134
159 https://doi.org/10.1186/1748-7161-9-7
160 rdf:type schema:CreativeWork
161 sg:pub.10.1186/1750-1326-6-31 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052296288
162 https://doi.org/10.1186/1750-1326-6-31
163 rdf:type schema:CreativeWork
164 sg:pub.10.1186/ar3391 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051225804
165 https://doi.org/10.1186/ar3391
166 rdf:type schema:CreativeWork
167 sg:pub.10.1186/s13013-015-0054-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007831386
168 https://doi.org/10.1186/s13013-015-0054-7
169 rdf:type schema:CreativeWork
170 https://app.dimensions.ai/details/publication/pub.1077319278 schema:CreativeWork
171 https://doi.org/10.1002/jbmr.2281 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001680042
172 rdf:type schema:CreativeWork
173 https://doi.org/10.1002/jor.22090 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032002643
174 rdf:type schema:CreativeWork
175 https://doi.org/10.1016/j.cyto.2010.12.018 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035076861
176 rdf:type schema:CreativeWork
177 https://doi.org/10.1016/j.neubiorev.2008.01.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006348241
178 rdf:type schema:CreativeWork
179 https://doi.org/10.1016/j.regpep.2013.03.022 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026622117
180 rdf:type schema:CreativeWork
181 https://doi.org/10.1016/j.spinee.2015.03.014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039448331
182 rdf:type schema:CreativeWork
183 https://doi.org/10.1056/nejmoa0708801 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005744340
184 rdf:type schema:CreativeWork
185 https://doi.org/10.1080/10408363.2016.1190683 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009242622
186 rdf:type schema:CreativeWork
187 https://doi.org/10.1086/519795 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019061180
188 rdf:type schema:CreativeWork
189 https://doi.org/10.1093/bioinformatics/bth457 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008081196
190 rdf:type schema:CreativeWork
191 https://doi.org/10.1097/00007632-200204010-00010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040515546
192 rdf:type schema:CreativeWork
193 https://doi.org/10.1097/blo.0b013e31811f39fa schema:sameAs https://app.dimensions.ai/details/publication/pub.1042945813
194 rdf:type schema:CreativeWork
195 https://doi.org/10.1097/brs.0000000000000807 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005844942
196 rdf:type schema:CreativeWork
197 https://doi.org/10.1097/brs.0b013e3181cf39ff schema:sameAs https://app.dimensions.ai/details/publication/pub.1008278255
198 rdf:type schema:CreativeWork
199 https://doi.org/10.1126/science.152.3723.711 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062488495
200 rdf:type schema:CreativeWork
201 https://doi.org/10.1155/2018/9784083 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105625537
202 rdf:type schema:CreativeWork
203 https://doi.org/10.1159/000119108 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027216506
204 rdf:type schema:CreativeWork
205 https://doi.org/10.1176/appi.ajp.160.4.636 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063495220
206 rdf:type schema:CreativeWork
207 https://doi.org/10.1177/147323000903700102 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005458972
208 rdf:type schema:CreativeWork
209 https://doi.org/10.2217/fon.09.66 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053579381
210 rdf:type schema:CreativeWork
211 https://doi.org/10.2217/pme.12.117 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034537175
212 rdf:type schema:CreativeWork
213 https://doi.org/10.3109/09513590.2013.879854 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031820213
214 rdf:type schema:CreativeWork
215 https://www.grid.ac/institutes/grid.14848.31 schema:alternateName University of Montreal
216 schema:name Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada. alain.moreau@recherche-ste-justine.qc.ca.
217 Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
218 Department of Nutrition, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
219 Department of Stomatology, Faculty of Dentistry, Université de Montréal, Montreal, QC, Canada. alain.moreau@recherche-ste-justine.qc.ca.
220 Faculty of Dentistry, Université de Montréal, Montreal, QC, Canada.
221 Program of Biomedical Sciences, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
222 Program of Biomedical Sciences, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada. alain.moreau@recherche-ste-justine.qc.ca.
223 Sainte-Justine University Hospital Research Center, Montreal, QC, Canada.
224 Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital, Research Center, Montreal, QC, Canada.
225 Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital, Research Center, Montreal, QC, Canada. alain.moreau@recherche-ste-justine.qc.ca.
226 rdf:type schema:Organization
227 https://www.grid.ac/institutes/grid.253555.1 schema:alternateName California State University, Chico
228 schema:name Department of Biological Sciences, California State University, Chico, CA, USA.
229 Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital, Research Center, Montreal, QC, Canada.
230 rdf:type schema:Organization
231 https://www.grid.ac/institutes/grid.59062.38 schema:alternateName University of Vermont
232 schema:name Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA.
233 Neuroscience, Behavior, and Health Initiative, University of Vermont, Burlington, Vermont, USA.
234 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...