Article: Association of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risk
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- Publisher Website: 10.1007/s00198-011-1861-1
- Scopus: eid_2-s2.0-84863564753
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| Title | Association of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risk | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Authors | Xiao, SM1 Gao, Y1 Cheung, CL1 Bow, CH1 Lau, KS1 Sham, PC1 Tan, KCB1 Kung, AWC1 | ||||||||||
| Keywords | Association BMD CDX1 Periostin Vertebral fracture | ||||||||||
| Issue Date | 2012 | ||||||||||
| Publisher | Springer 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?] DOI: http://dx.doi.org/10.1007/s00198-011-1861-1 | ||||||||||
| 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. | ||||||||||
| ISSN | 0937-941X 2011 Impact Factor: 4.58 2011 SCImago Journal Rankings: 0.341 | ||||||||||
| DOI | http://dx.doi.org/10.1007/s00198-011-1861-1 | ||||||||||
| ISI Accession Number ID | WOS:000304878900006
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 | References in Scopus | ||||||||||
| Grants | Replication and Functional Study of Polymorphisms in miRNA Binding Sites and Osteoporosis To determine the functional variants of candidate genes identified by Genome-wide Association Study of Osteoporosis |
| dc.contributor.author | Xiao, SM | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Gao, Y | ||||||||||
| dc.contributor.author | Cheung, CL | ||||||||||
| dc.contributor.author | Bow, CH | ||||||||||
| dc.contributor.author | Lau, KS | ||||||||||
| dc.contributor.author | Sham, PC | ||||||||||
| dc.contributor.author | Tan, KCB | ||||||||||
| dc.contributor.author | Kung, AWC | ||||||||||
| dc.date.accessioned | 2012-05-28T08:52:14Z | ||||||||||
| dc.date.available | 2012-05-28T08:52:14Z | ||||||||||
| dc.date.issued | 2012 | ||||||||||
| dc.description.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. | ||||||||||
| dc.description.grant | Replication and Functional Study of Polymorphisms in miRNA Binding Sites and Osteoporosis | ||||||||||
| dc.description.grant | To determine the functional variants of candidate genes identified by Genome-wide Association Study of Osteoporosis | ||||||||||
| dc.description.grantcode | 104089 | ||||||||||
| dc.description.grantcode | 103718 | ||||||||||
| dc.description.nature | published_or_final_version | ||||||||||
| dc.description.other | Springer Open Choice, 28 May 2012 | ||||||||||
| dc.identifier.citation | Osteoporosis 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.citeulike | 10214653 | ||||||||||
| dc.identifier.doi | http://dx.doi.org/10.1007/s00198-011-1861-1 | ||||||||||
| dc.identifier.eissn | 1433-2965 | ||||||||||
| dc.identifier.epage | 1887 | ||||||||||
| dc.identifier.hkuros | 201497 | ||||||||||
| dc.identifier.isi | WOS:000304878900006
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.issn | 0937-941X 2011 Impact Factor: 4.58 2011 SCImago Journal Rankings: 0.341 | ||||||||||
| dc.identifier.issue | 7 | ||||||||||
| dc.identifier.openurl | | ||||||||||
| dc.identifier.scopus | eid_2-s2.0-84863564753 | ||||||||||
| dc.identifier.spage | 1877 | ||||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/147142 | ||||||||||
| dc.identifier.volume | 23 | ||||||||||
| dc.language | Eng | ||||||||||
| dc.publisher | Springer U K. The Journal's web site is located at http://www.springer.com/medicine/orthopedics/journal/198 | ||||||||||
| dc.publisher.place | United Kingdom | ||||||||||
| dc.relation.ispartof | Osteoporosis International | ||||||||||
| dc.relation.references | References in Scopus | ||||||||||
| dc.rights | The Author(s) | ||||||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||||||
| dc.subject | Association | ||||||||||
| dc.subject | BMD | ||||||||||
| dc.subject | CDX1 | ||||||||||
| dc.subject | Periostin | ||||||||||
| dc.subject | Vertebral fracture | ||||||||||
| dc.title | Association of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risk | ||||||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong