{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T15:14:46Z","timestamp":1772032486710,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871747 81661168013 8197090027 81772304 81972029"],"award-info":[{"award-number":["81871747 81661168013 8197090027 81772304 81972029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Previous studies have shown that <jats:italic>LBX1<\/jats:italic> is associated with adolescent idiopathic scoliosis (AIS) in multiple populations. For the first time, rs1322330 located in the putative promoter region of <jats:italic>LBX1<\/jats:italic> was found significantly associated with AIS in the Chinese population [<jats:italic>p<\/jats:italic>\u00a0=\u00a06.08\u00a0\u00d7\u00a010<jats:sup>\u201314<\/jats:sup>, odds ratio (OR)\u00a0=\u00a01.42, 95% confidence interval of 1.03\u20131.55]. Moreover, the luciferase assay and electrophoretic mobility shift assay supported that the allele A of rs1322330 could down-regulate the expression of <jats:italic>LBX1<\/jats:italic> in the paraspinal muscles of AIS. In addition, silencing <jats:italic>LBX1<\/jats:italic> in the myosatellite cells resulted in significantly inhibited cell viability and myotube formation, which supported an essential role of <jats:italic>LBX1<\/jats:italic> in muscle development of AIS. To summarize, rs1322330 may be a novel functional SNP regulating the expression of <jats:italic>LBX1<\/jats:italic>, which was involved in the etiology of AIS possibly <jats:italic>via<\/jats:italic> regulation of myogenesis in the paraspinal muscles.<\/jats:p>","DOI":"10.3389\/fcell.2021.777890","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T20:30:48Z","timestamp":1638390648000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["A Functional SNP in the Promoter of LBX1 Is Associated With the Development of Adolescent Idiopathic Scoliosis Through Involvement in the Myogenesis of Paraspinal Muscles"],"prefix":"10.3389","volume":"9","author":[{"given":"Leilei","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenhua","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhicheng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wayne Y. W.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhichong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelson","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack Chun-Yiu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zezhang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1242\/dev.127.2.437","article-title":"The Role of Lbx1 in Migration of Muscle Precursor Cells","volume":"127","author":"Brohmann","year":"2000","journal-title":"Development"},{"key":"B2","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1101\/gr.5582207","article-title":"The ENCODEdb Portal: Simplified Access to ENCODE Consortium Data","volume":"17","author":"Elnitski","year":"2007","journal-title":"Genome Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1152\/japplphysiol.00031.2011","article-title":"Improved Fatigue Resistance in Gs\u03b1-Deficient and Aging Mouse Skeletal Muscles Due to Adaptive Increases in Slow Fibers","volume":"111","author":"Feng","year":"2011","journal-title":"J. Appl. Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1002\/ajmg.a.36589","article-title":"Microduplication 10q24.31 in a Spanish Girl With Scoliosis and Myopathy: The Critical Role ofLBX","volume":"164","author":"Fern\u00e1ndez-Ja\u00e9n","year":"2014","journal-title":"Am. J. Med. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1097\/00007632-198405000-00008","article-title":"Paraspinal Muscle Imbalance in Adolescent Idiopathic Scoliosis","volume":"9","author":"Ford","year":"1984","journal-title":"Spine"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1016\/j.spinee.2015.05.013","article-title":"Candidate Gene Analysis and Exome Sequencing Confirm LBX1 as a Susceptibility Gene for Idiopathic Scoliosis","volume":"15","author":"Grauers","year":"2015","journal-title":"Spine J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1242\/dev.127.2.413","article-title":"Lbx1 is Required for Muscle Precursor Migration Along a Lateral Pathway into the Limb","volume":"127","author":"Gross","year":"2000","journal-title":"Development"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e1005802","DOI":"10.1371\/journal.pgen.1005802","article-title":"Functional Investigation of a Non-Coding Variant Associated with Adolescent Idiopathic Scoliosis in Zebrafish: Elevated Expression of the Ladybird Homeobox Gene Causes Body Axis Deformation","volume":"12","author":"Guo","year":"2016","journal-title":"Plos Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"C525","DOI":"10.1152\/ajpcell.00259.2007","article-title":"Myostatin Regulates Fiber-Type Composition of Skeletal Muscle by Regulating MEF2 and MyoD Gene Expression","volume":"296","author":"Hennebry","year":"2009","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1152\/japplphysiol.00361.2013","article-title":"The Influence of Training Status, Age, and Muscle Fiber Type on Cycling Efficiency and Endurance Performance","volume":"115","author":"Hopker","year":"2013","journal-title":"J. Appl. Physiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e37702","DOI":"10.1371\/journal.pone.0037702","article-title":"Gas7-Deficient Mouse Reveals Roles in Motor Function and Muscle Fiber Composition during Aging","volume":"7","author":"Huang","year":"2012","journal-title":"PLoS One"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1097\/00007632-200211010-00009","article-title":"Association Between Estrogen Receptor Gene Polymorphisms and Curve Severity of Idiopathic Scoliosis","volume":"27","author":"Inoue","year":"2002","journal-title":"Spine"},{"key":"B13","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1007\/s00586-012-2532-4","article-title":"Association of rs11190870 Near LBX1 With Adolescent Idiopathic Scoliosis Susceptibility in a Han Chinese Population","volume":"22","author":"Jiang","year":"2013","journal-title":"Eur. Spine J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The Human Genome Browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/ng.2639","article-title":"Genetic Variants in GPR126 are Associated With Adolescent Idiopathic Scoliosis","volume":"45","author":"Kou","year":"2013","journal-title":"Nat. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2898","DOI":"10.1097\/BRS.0b013e3181891751","article-title":"The Pathogenesis of Adolescent Idiopathic Scoliosis","volume":"33","author":"Kouwenhoven","year":"2008","journal-title":"Spine"},{"key":"B17","doi-asserted-by":"publisher","first-page":"55918","DOI":"10.3791\/55918","article-title":"Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-Operated Calcium Entry Measurement","author":"Laumonier","year":"2017","journal-title":"J. Vis. Exp."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1007\/s00586-016-4802-z","article-title":"Clinical Balance Tests, Proprioceptive System and Adolescent Idiopathic Scoliosis","volume":"26","author":"Le Berre","year":"2017","journal-title":"Eur. Spine J."},{"key":"B19","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1002\/gepi.21690","article-title":"MaCH-Admix: Genotype Imputation for Admixed Populations","volume":"37","author":"Liu","year":"2013","journal-title":"Genet. Epidemiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1097\/BRS.0b013e3181c6ba13","article-title":"Lack of Association Between the Promoter Polymorphisms of MMP-3 and IL-6 Genes and Adolescent Idiopathic Scoliosis","volume":"35","author":"Liu","year":"2010","journal-title":"Spine"},{"key":"B21","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1097\/BLO.0b013e318126c062","article-title":"Genetics of Familial Idiopathic Scoliosis","volume":"462","author":"Miller","year":"2007","journal-title":"Clin. Orthop. Relat. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1097\/01.brs.0000162282.46160.0a","article-title":"Identification of Candidate Regions for Familial Idiopathic Scoliosis","volume":"30","author":"Miller","year":"2005","journal-title":"Spine"},{"key":"B23","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1002\/jor.1100140621","article-title":"Genetic Analysis of Structural Elastic Fiber and Collagen Genes in Familial Adolescent Idiopathic Scoliosis","volume":"14","author":"Miller","year":"1996","journal-title":"J. Orthop. Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1097\/01.BRS.0000083235.74593.49","article-title":"Allelic Variants of Human Melatonin 1A Receptor in Patients with Familial Adolescent Idiopathic Scoliosis","volume":"28","author":"Morcuende","year":"2003","journal-title":"Spine"},{"key":"B25","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/bf00301328","article-title":"The Development of Adolescent Idiopathic Scoliosis","volume":"5","author":"Murray","year":"1996","journal-title":"Eur. Spine J."},{"key":"B26","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1097\/BRS.0000000000002280","article-title":"A Replication Study for Association of LBX1 Locus With Adolescent Idiopathic Scoliosis in French-Canadian Population","volume":"43","author":"Nada","year":"2018","journal-title":"Spine"},{"key":"B27","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.ajhg.2015.06.012","article-title":"A Functional SNP in BNC2 is Associated with Adolescent Idiopathic Scoliosis","volume":"97","author":"Ogura","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1093\/bioinformatics\/btq419","article-title":"LocusZoom: Regional Visualization of Genome-Wide Association Scan Results","volume":"26","author":"Pruim","year":"2010","journal-title":"Bioinformatics"},{"key":"B29","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a Tool Set for Whole-Genome Association and Population-Based Linkage Analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"B30","doi-asserted-by":"publisher","first-page":"236","DOI":"10.5606\/tftrd.2019.2825","article-title":"Evaluation of Balance in Young Adults With Idiopathic Scoliosis","volume":"65","author":"\u015eahin","year":"2019","journal-title":"Turk J. Phys. Med. Rehab"},{"key":"B31","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1002\/jcb.1084","article-title":"Interferon Regulatory Factor 1 Promoter Polymorphism and Response to Type 1 Interferon","volume":"81","author":"Saito","year":"2001","journal-title":"J. Cell. Biochem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e924415","DOI":"10.12659\/MSM.924415","article-title":"Fiber Type-Specific Morphological and Cellular Changes of Paraspinal Muscles in Patients with Severe Adolescent Idiopathic Scoliosis","volume":"26","author":"Shao","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1093\/hmg\/ddq571","article-title":"Genome-wide Association Studies of Adolescent Idiopathic Scoliosis Suggest Candidate Susceptibility Genes","volume":"20","author":"Sharma","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"B34","doi-asserted-by":"publisher","first-page":"6452","DOI":"10.1038\/ncomms7452","article-title":"A PAX1 Enhancer Locus Is Associated with Susceptibility to Idiopathic Scoliosis in Females","volume":"6","author":"Sharma","year":"2015","journal-title":"Nat. Commun."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1038\/ng.974","article-title":"A Genome-Wide Association Study Identifies Common Variants Near LBX1 Associated With Adolescent Idiopathic Scoliosis","volume":"43","author":"Takahashi","year":"","journal-title":"Nat. Genet."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1002\/jor.21347","article-title":"Lack of Association between Adolescent Idiopathic Scoliosis and Previously Reported Single Nucleotide Polymorphisms in MATN1, MTNR1B, TPH1, and IGF1 in a Japanese Population","volume":"29","author":"Takahashi","year":"","journal-title":"J. Orthop. Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e5880","DOI":"10.1371\/journal.pone.0005880","article-title":"Regulation of Slow and Fast Muscle Myofibrillogenesis by Wnt\/\u03b2-Catenin and Myostatin Signaling","volume":"4","author":"Tee","year":"2009","journal-title":"PLoS One"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e598","DOI":"10.1097\/MD.0000000000000598","article-title":"Histochemical Analysis of Paraspinal Rotator Muscles From Patients With Adolescent Idiopathic Scoliosis","volume":"94","author":"Wajchenberg","year":"2015","journal-title":"Medicine (Baltimore)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.cca.2009.12.004","article-title":"A Potential Regulatory Single Nucleotide Polymorphism in the Promoter of the Klotho Gene may be Associated with Essential Hypertension in the Chinese Han Population","volume":"411","author":"Wang","year":"2010","journal-title":"Clinica Chim. Acta"},{"key":"B40","doi-asserted-by":"publisher","first-page":"D930","DOI":"10.1093\/nar\/gkr917","article-title":"HaploReg: A Resource for Exploring Chromatin States, Conservation, and Regulatory Motif Alterations within Sets of Genetically Linked Variants","volume":"40","author":"Ward","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"4178","DOI":"10.1242\/jcs.011668","article-title":"Functional Analysis of Homeodomain-Containing Transcription Factor Lbx1 in Satellite Cells of Mouse Skeletal Muscle","volume":"120","author":"Watanabe","year":"2007","journal-title":"J. Cell Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"E677","DOI":"10.1097\/BRS.0000000000003409","article-title":"Asymmetric Expression of Wnt\/B-Catenin Pathway in AIS","volume":"45","author":"Xu","year":"2020","journal-title":"Spine"},{"key":"B43","doi-asserted-by":"publisher","first-page":"8355","DOI":"10.1038\/ncomms9355","article-title":"Genome-Wide Association Study Identifies New Susceptibility Loci for Adolescent Idiopathic Scoliosis in Chinese Girls","volume":"6","author":"Zhu","year":"2015","journal-title":"Nat. Commun."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1093\/hmg\/ddx045","article-title":"Genome-Wide Association Study Identifies Novel Susceptible Loci and Highlights Wnt\/Beta-Catenin Pathway in the Development of Adolescent Idiopathic Scoliosis","volume":"26","author":"Zhu","year":"2017","journal-title":"Hum. Mol. Genet."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.777890\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T20:30:51Z","timestamp":1638390651000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.777890\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,30]]},"references-count":44,"alternative-id":["10.3389\/fcell.2021.777890"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.777890","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,30]]},"article-number":"777890"}}