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Article: Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant.

TitleLumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant.
Authors
Issue Date2013
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal of Clinical Investigation, 2013, v. 123, n. 11, p. 4909-4917 How to Cite?
AbstractLumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family-based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR-513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA.
Persistent Identifierhttp://hdl.handle.net/10722/195662
ISSN
2015 Impact Factor: 12.575
2015 SCImago Journal Rankings: 8.764
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSong, Yen_US
dc.contributor.authorKarasugi, Ten_US
dc.contributor.authorCheung, KMCen_US
dc.contributor.authorChiba, Ken_US
dc.contributor.authorHo, DWHen_US
dc.contributor.authorMiyake, Aen_US
dc.contributor.authorKao, PYPen_US
dc.contributor.authorSze, KLen_US
dc.contributor.authorYee, FYAen_US
dc.contributor.authorTakahashi, Aen_US
dc.contributor.authorKawaguchi, Yen_US
dc.contributor.authorMikami, Yen_US
dc.contributor.authorMatsumoto, Men_US
dc.contributor.authorTogawa, Den_US
dc.contributor.authorKanayama, Men_US
dc.contributor.authorShi, Den_US
dc.contributor.authorDai, Jen_US
dc.contributor.authorJiang, Qen_US
dc.contributor.authorWu, Cen_US
dc.contributor.authorTian, Wen_US
dc.contributor.authorWang, Nen_US
dc.contributor.authorLeong, JCYen_US
dc.contributor.authorLuk, KDKen_US
dc.contributor.authorYip, SPen_US
dc.contributor.authorCherny, SSen_US
dc.contributor.authorWang, JJen_US
dc.contributor.authorMundlos, Sen_US
dc.contributor.authorKelempisioti, Aen_US
dc.contributor.authorEskola, PJen_US
dc.contributor.authorMannikko, Men_US
dc.contributor.authorMakela, Pen_US
dc.contributor.authorKarppinen, Jen_US
dc.contributor.authorJarvelin, MRen_US
dc.contributor.authorO'Reilly, PFen_US
dc.contributor.authorKubo, Men_US
dc.contributor.authorKimura, Ten_US
dc.contributor.authorKubo, Ten_US
dc.contributor.authorToyoma, Yen_US
dc.contributor.authorMizuta, Hen_US
dc.contributor.authorCheah, KSEen_US
dc.contributor.authorTsunoda, Ten_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorIkegawa, Sen_US
dc.contributor.authorChan, Den_US
dc.date.accessioned2014-03-07T04:21:33Z-
dc.date.available2014-03-07T04:21:33Z-
dc.date.issued2013en_US
dc.identifier.citationJournal of Clinical Investigation, 2013, v. 123, n. 11, p. 4909-4917en_US
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/10722/195662-
dc.description.abstractLumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family-based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR-513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA.-
dc.languageengen_US
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org-
dc.relation.ispartofJournal of Clinical Investigationen_US
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleLumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant.en_US
dc.typeArticleen_US
dc.identifier.emailSong, Y: songy@hku.hken_US
dc.identifier.emailCheung, KMC: cheungmc@hku.hken_US
dc.identifier.emailHo, DWH: dwhho@hku.hken_US
dc.identifier.emailKao, PYP: h0102925@graduate.hku.hken_US
dc.identifier.emailSze, KL: h0000175@hkusua.hku.hken_US
dc.identifier.emailYee, FYA: fyayee@hku.hken_US
dc.identifier.emailLeong, JCY: hrmolcy@hkucc.hku.hken_US
dc.identifier.emailLuk, KDK: hrmoldk@hkucc.hku.hken_US
dc.identifier.emailCherny, SS: cherny@hku.hken_US
dc.identifier.emailWang, JJ: junwen@hku.hken_US
dc.identifier.emailCheah, KSE: hrmbdkc@hku.hken_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.emailChan, D: chand@hku.hken_US
dc.identifier.authoritySong, Y=rp00488en_US
dc.identifier.authorityCheung, KMC=rp00387en_US
dc.identifier.authorityLuk, KDK=rp00333en_US
dc.identifier.authorityCherny, SS=rp00232en_US
dc.identifier.authorityWang, JJ=rp00280en_US
dc.identifier.authorityCheah, KSE=rp00342en_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.identifier.authorityChan, D=rp00540en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1172/JCI69277-
dc.identifier.pmid24216480-
dc.identifier.scopuseid_2-s2.0-84887462208-
dc.identifier.hkuros228232en_US
dc.identifier.volume123en_US
dc.identifier.spage4909en_US
dc.identifier.epage4917en_US
dc.identifier.isiWOS:000326611900036-

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