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Association of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risk
Authors
A Kruzynska-Frejtag
A Lindsley
+42 more
A Oshima
A. W. C. Kung
AD Tabensky
AW Kung
AW Kung
AW Kung
C. H. Bow
C.-L. Cheung
CL Cheung
CL Cheung
DL Coutu
DM Black
DP Kiel
GR Abecasis
HY Yuan
J Cordey
J Dequeker
J Litvin
JB Richards
JM Kaufman
K Horiuchi
K. C. B. Tan
K.-S. Lau
LW Hahn
MS Lee
MY Ng
N Bonnet
Diagnosis, and Therapy NIH Consensus Development Panel on Osteoporosis Prevention
NK Arden
P. C. Sham
QY Huang
RJ Guo
RP Gersch
S Purcell
S Purcell
S Takeshita
S.-M. Xiao
T Kawamoto
U Styrkarsdottir
U Styrkarsdottir
V Subramanian
Y. Gao
Publication date
1 January 2011
Publisher
Springer-Verlag
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PubMed
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.published_or_final_versionSpringer Open Choice, 28 May 201
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info:doi/10.1007%2Fs00198-011-...
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