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Article: Association of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risk
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TitleAssociation of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risk
 
AuthorsXiao, SM1 1 1
Gao, Y1
Cheung, CL1
Bow, CH1
Lau, KS1
Sham, PC1 1
Tan, KCB1 1
Kung, AWC1 1
 
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
 
CitationOsteoporosis International, 2012, v. 23 n. 7, p. 1877-1887 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00198-011-1861-1
 
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.
 
ISSN0937-941X
2012 Impact Factor: 4.039
2012 SCImago Journal Rankings: 1.524
 
DOIhttp://dx.doi.org/10.1007/s00198-011-1861-1
 
ISI Accession Number IDWOS:000304878900006
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.

 
ReferencesReferences in Scopus
 
GrantsTo determine the functional variants of candidate genes identified by Genome-wide Association Study of Osteoporosis
 
DC FieldValue
dc.contributor.authorXiao, SM
 
dc.contributor.authorGao, Y
 
dc.contributor.authorCheung, CL
 
dc.contributor.authorBow, CH
 
dc.contributor.authorLau, KS
 
dc.contributor.authorSham, PC
 
dc.contributor.authorTan, KCB
 
dc.contributor.authorKung, AWC
 
dc.date.accessioned2012-05-28T08:52:14Z
 
dc.date.available2012-05-28T08:52:14Z
 
dc.date.issued2012
 
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.
 
dc.description.naturepublished_or_final_version
 
dc.description.otherSpringer Open Choice, 28 May 2012
 
dc.identifier.citationOsteoporosis International, 2012, v. 23 n. 7, p. 1877-1887 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00198-011-1861-1
 
dc.identifier.citeulike10214653
 
dc.identifier.doihttp://dx.doi.org/10.1007/s00198-011-1861-1
 
dc.identifier.eissn1433-2965
 
dc.identifier.epage1887
 
dc.identifier.hkuros201497
 
dc.identifier.isiWOS:000304878900006
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.

 
dc.identifier.issn0937-941X
2012 Impact Factor: 4.039
2012 SCImago Journal Rankings: 1.524
 
dc.identifier.issue7
 
dc.identifier.openurl
 
dc.identifier.pmid22215184
 
dc.identifier.scopuseid_2-s2.0-84863564753
 
dc.identifier.spage1877
 
dc.identifier.urihttp://hdl.handle.net/10722/147142
 
dc.identifier.volume23
 
dc.languageEng
 
dc.publisherSpringer U K. The Journal's web site is located at http://www.springer.com/medicine/orthopedics/journal/198
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofOsteoporosis International
 
dc.relation.projectTo determine the functional variants of candidate genes identified by Genome-wide Association Study of Osteoporosis
 
dc.relation.referencesReferences in Scopus
 
dc.rightsThe Author(s)
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshAdult
 
dc.subject.meshAged
 
dc.subject.meshBinding Sites - genetics
 
dc.subject.meshBone Density - genetics
 
dc.subject.meshCell Adhesion Molecules - genetics - metabolism
 
dc.subject.meshFemale
 
dc.subject.meshGenetic Predisposition to Disease
 
dc.subject.meshGenotype
 
dc.subject.meshHomeodomain Proteins - metabolism
 
dc.subject.meshHumans
 
dc.subject.meshMale
 
dc.subject.meshMiddle Aged
 
dc.subject.meshOsteoporotic Fractures - genetics - physiopathology
 
dc.subject.meshPolymorphism, Single Nucleotide
 
dc.subject.meshProtein Binding - genetics
 
dc.subject.meshSpinal Fractures - genetics - physiopathology
 
dc.subjectAssociation
 
dc.subjectBMD
 
dc.subjectCDX1
 
dc.subjectPeriostin
 
dc.subjectVertebral fracture
 
dc.titleAssociation of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risk
 
dc.typeArticle
 
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<contributor.author>Bow, CH</contributor.author>
<contributor.author>Lau, KS</contributor.author>
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Author Affiliations
  1. The University of Hong Kong