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Article: Association of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risk

TitleAssociation of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risk
Authors
KeywordsAssociation
BMD
CDX1
Periostin
Vertebral fracture
Issue Date2012
PublisherSpringer U K. The Journal's web site is located at http://www.springer.com/medicine/orthopedics/journal/198
Citation
Osteoporosis International, 2012, v. 23 n. 7, p. 1877-1887 How to Cite?
Abstract
Summary Periostin (POSTN) as a regulator of osteoblast differentiation and bone formation may affect susceptibility to osteoporosis. This study suggests POSTN as a candidate gene for bone mineral density (BMD) variation and vertebral fracture risk, which could better our understanding about the genetic pathogenesis of osteoporosis and will be useful in clinic in the future. Introduction The genetic determination of osteoporosis is complex and ill-defined. Periostin (POSTN), an extracellular matrix secreted by osteoblasts and a regulator of osteoblast differentiation and bone formation, may affect susceptibility to osteoporosis. Methods We adopted a tag-single nucleotide polymorphism (SNP) based association method followed by imputationbased verification and identification of a causal variant. The association was investigated in 1,572 subjects with extremeBMD and replicated in an independent population of 2,509 subjects. BMD was measured by dual X-ray absorptiometry. Vertebral fractures were identified by assessing vertebral height from X-rays of the thoracolumbar spine. Association analyses were performed with PLINK toolset and imputation analyses with MACH software. The top imputation finding was subsequently validated by genotyping. Interactions between POSTN and another BMD-related candidate gene sclerostin (SOST) were analyzed using MDR program and validated by logistical regression analyses. The putative transcription factor binding with target sequence was confirmed by electrophoretic mobility shift assay (EMSA). Results Several SNPs of POSTN were associated with BMD or vertebral fractures. The most significant polymorphism was rs9547970, located at the -2,327bpupstream(P06.8×10-4)of POSTN. Carriers of the minor allele G per copy of rs9547970 had1.33higherriskofvertebralfracture(P00. 007). An interactive effect between POSTN and SOST upon BMD variation was suggested (P<0.01). A specific binding of CDX1 to the sequence of POSTN with the major allele A of rs9547970 but not the variant G allele was confirmed by EMSA. Conclusions Our results suggest POSTN as a candidate gene for BMD variation and vertebral fracture risk. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation.
Persistent Identifierhttp://hdl.handle.net/10722/147142
ISSN
2013 Impact Factor: 4.165
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant CouncilHKU 768610M
NSFC/GRCN-HKU-715/07
KC Wong Education Foundation
University of Hong Kong201007176237
Funding Information:

This project is supported by Hong Kong Research Grant Council (HKU 768610M), NSFC/GRC Joint Research Scheme N-HKU-715/07, The KC Wong Education Foundation, and The Bone Health Fund, Seed Funding for Basic Research, Small Project Funding (201007176237), Osteoporosis and Endocrine Research Fund, The University of Hong Kong.

References
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Author Affiliations
  1. The University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorXiao, SMen_HK
dc.contributor.authorGao, Yen_HK
dc.contributor.authorCheung, CLen_HK
dc.contributor.authorBow, CHen_HK
dc.contributor.authorLau, KSen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorTan, KCBen_HK
dc.contributor.authorKung, AWCen_HK
dc.date.accessioned2012-05-28T08:52:14Z-
dc.date.available2012-05-28T08:52:14Z-
dc.date.issued2012en_HK
dc.identifier.citationOsteoporosis International, 2012, v. 23 n. 7, p. 1877-1887en_HK
dc.identifier.issn0937-941Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/147142-
dc.description.abstractSummary Periostin (POSTN) as a regulator of osteoblast differentiation and bone formation may affect susceptibility to osteoporosis. This study suggests POSTN as a candidate gene for bone mineral density (BMD) variation and vertebral fracture risk, which could better our understanding about the genetic pathogenesis of osteoporosis and will be useful in clinic in the future. Introduction The genetic determination of osteoporosis is complex and ill-defined. Periostin (POSTN), an extracellular matrix secreted by osteoblasts and a regulator of osteoblast differentiation and bone formation, may affect susceptibility to osteoporosis. Methods We adopted a tag-single nucleotide polymorphism (SNP) based association method followed by imputationbased verification and identification of a causal variant. The association was investigated in 1,572 subjects with extremeBMD and replicated in an independent population of 2,509 subjects. BMD was measured by dual X-ray absorptiometry. Vertebral fractures were identified by assessing vertebral height from X-rays of the thoracolumbar spine. Association analyses were performed with PLINK toolset and imputation analyses with MACH software. The top imputation finding was subsequently validated by genotyping. Interactions between POSTN and another BMD-related candidate gene sclerostin (SOST) were analyzed using MDR program and validated by logistical regression analyses. The putative transcription factor binding with target sequence was confirmed by electrophoretic mobility shift assay (EMSA). Results Several SNPs of POSTN were associated with BMD or vertebral fractures. The most significant polymorphism was rs9547970, located at the -2,327bpupstream(P06.8×10-4)of POSTN. Carriers of the minor allele G per copy of rs9547970 had1.33higherriskofvertebralfracture(P00. 007). An interactive effect between POSTN and SOST upon BMD variation was suggested (P<0.01). A specific binding of CDX1 to the sequence of POSTN with the major allele A of rs9547970 but not the variant G allele was confirmed by EMSA. Conclusions Our results suggest POSTN as a candidate gene for BMD variation and vertebral fracture risk. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation.en_HK
dc.languageEngen_US
dc.publisherSpringer U K. The Journal's web site is located at http://www.springer.com/medicine/orthopedics/journal/198en_HK
dc.relation.ispartofOsteoporosis Internationalen_HK
dc.rightsThe Author(s)en_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong Licenseen_US
dc.subjectAssociationen_HK
dc.subjectBMDen_HK
dc.subjectCDX1en_HK
dc.subjectPeriostinen_HK
dc.subjectVertebral fractureen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshBinding Sites - geneticsen_HK
dc.subject.meshBone Density - geneticsen_HK
dc.subject.meshCell Adhesion Molecules - genetics - metabolismen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGenetic Predisposition to Diseaseen_HK
dc.subject.meshGenotypeen_HK
dc.subject.meshHomeodomain Proteins - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshOsteoporotic Fractures - genetics - physiopathologyen_HK
dc.subject.meshPolymorphism, Single Nucleotideen_HK
dc.subject.meshProtein Binding - geneticsen_HK
dc.subject.meshSpinal Fractures - genetics - physiopathologyen_HK
dc.titleAssociation of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risken_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://www.springerlink.com/link-out/?id=2104&code=0545JT873Q17G264&MUD=MPen_US
dc.identifier.emailCheung, CL: lung1212@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailTan, KCB: kcbtan@hku.hken_HK
dc.identifier.emailKung, AWC: awckung@hku.hken_HK
dc.identifier.authorityCheung, CL=rp01749en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityTan, KCB=rp00402en_HK
dc.identifier.authorityKung, AWC=rp00368en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1007/s00198-011-1861-1en_HK
dc.identifier.pmid22215184en_HK
dc.identifier.scopuseid_2-s2.0-84863564753en_HK
dc.identifier.hkuros201497-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84863564753&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume23en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1877en_HK
dc.identifier.epage1887en_HK
dc.identifier.eissn1433-2965en_US
dc.identifier.isiWOS:000304878900006-
dc.publisher.placeUnited Kingdomen_HK
dc.description.otherSpringer Open Choice, 28 May 2012en_US
dc.relation.projectTo determine the functional variants of candidate genes identified by Genome-wide Association Study of Osteoporosis-
dc.identifier.scopusauthoridXiao, SM=7402022586en_HK
dc.identifier.scopusauthoridGao, Y=34876578200en_HK
dc.identifier.scopusauthoridCheung, CL=14520953400en_HK
dc.identifier.scopusauthoridBow, CH=36055977600en_HK
dc.identifier.scopusauthoridLau, KS=35205833900en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridTan, KCB=8082703100en_HK
dc.identifier.scopusauthoridKung, AWC=7102322339en_HK
dc.identifier.citeulike10214653-

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