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Article: Identification of LTBP2 on chromosome 14q as a novel candidate gene for bone mineral density variation and fracture risk association

TitleIdentification of LTBP2 on chromosome 14q as a novel candidate gene for bone mineral density variation and fracture risk association
Authors
Issue Date2008
PublisherThe Endocrine Society. The Journal's web site is located at http://jcem.endojournals.org
Citation
Journal Of Clinical Endocrinology And Metabolism, 2008, v. 93 n. 11, p. 4448-4455 How to Cite?
AbstractContext: Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Chromosome 14q has previously been linked to BMD variation in several genome-wide linkage scans in Caucasian populations. Objective: Our objective was to replicate and identify the novel candidate genes in the quantitative trait loci (QTL) at chromosome 14q QTL. Subjects and Methods: Eighteen microsatellite markers were genotyped for a 117-cM interval in 306 Southern Chinese pedigrees with 1459 subjects. Successful replication of the QTL was confirmed within this region for trochanter and total hip BMD. Using a gene prioritization approach as implemented in the Endeavour program, we genotyped 65 single-nucleotide polymorphisms in the top five ranking candidate genes within the linkage peak in 706 and 760 case-control subject pairs with extremely high and low trochanter and total hip BMD, respectively. Results: Single-marker and haplotype analyses revealed that ESR2 and latent TGF-β binding protein 2 (LTBP2) had significant associations with trochanter and total hip BMD. Multiple logistic regression revealed a strong genetic association between LTBP2 gene locus and total hip BMD variation (P = 0.0004) and prevalent fracture (P = 0.01). Preliminary in vitro study showed differential expression of LTBP2 gene in MC3T3-E1 mouse preosteoblastic cells in culture. Conclusions: Apart from ESR2, LTBP2 is a novel positional candidate gene in chromosome 14q QTL for BMD variation and fracture. Copyright © 2008 by The Endocrine Society.
Persistent Identifierhttp://hdl.handle.net/10722/139671
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.940
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant Council
Bone Health Fund
HKU Foundation and Matching Grant
University of Hong Kong
Funding Information:

This project is supported by Hong Kong Research Grant Council; The Bone Health Fund, HKU Foundation and Matching Grant, The University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorCheung, CLen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorChan, Ven_HK
dc.contributor.authorPaterson, ADen_HK
dc.contributor.authorLuk, KDKen_HK
dc.contributor.authorKung, AWCen_HK
dc.date.accessioned2011-09-23T05:53:26Z-
dc.date.available2011-09-23T05:53:26Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Clinical Endocrinology And Metabolism, 2008, v. 93 n. 11, p. 4448-4455en_HK
dc.identifier.issn0021-972Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/139671-
dc.description.abstractContext: Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Chromosome 14q has previously been linked to BMD variation in several genome-wide linkage scans in Caucasian populations. Objective: Our objective was to replicate and identify the novel candidate genes in the quantitative trait loci (QTL) at chromosome 14q QTL. Subjects and Methods: Eighteen microsatellite markers were genotyped for a 117-cM interval in 306 Southern Chinese pedigrees with 1459 subjects. Successful replication of the QTL was confirmed within this region for trochanter and total hip BMD. Using a gene prioritization approach as implemented in the Endeavour program, we genotyped 65 single-nucleotide polymorphisms in the top five ranking candidate genes within the linkage peak in 706 and 760 case-control subject pairs with extremely high and low trochanter and total hip BMD, respectively. Results: Single-marker and haplotype analyses revealed that ESR2 and latent TGF-β binding protein 2 (LTBP2) had significant associations with trochanter and total hip BMD. Multiple logistic regression revealed a strong genetic association between LTBP2 gene locus and total hip BMD variation (P = 0.0004) and prevalent fracture (P = 0.01). Preliminary in vitro study showed differential expression of LTBP2 gene in MC3T3-E1 mouse preosteoblastic cells in culture. Conclusions: Apart from ESR2, LTBP2 is a novel positional candidate gene in chromosome 14q QTL for BMD variation and fracture. Copyright © 2008 by The Endocrine Society.en_HK
dc.languageengen_US
dc.publisherThe Endocrine Society. The Journal's web site is located at http://jcem.endojournals.orgen_HK
dc.relation.ispartofJournal of Clinical Endocrinology and Metabolismen_HK
dc.subject.meshBone Density - genetics-
dc.subject.meshChromosomes, Human, Pair 14-
dc.subject.meshFractures, Bone - epidemiology - genetics-
dc.subject.meshLatent TGF-beta Binding Proteins - genetics-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.titleIdentification of LTBP2 on chromosome 14q as a novel candidate gene for bone mineral density variation and fracture risk associationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-972X&volume=93&issue=11&spage=4448&epage=4455&date=2008&atitle=Identification+of+LTBP2+on+chromosome+14q+as+a+novel+candidate+gene+for+bone+mineral+density+variation+and+fracture+risk+association-
dc.identifier.emailCheung, CL: lung1212@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailChan, V: vnychana@hkucc.hku.hken_HK
dc.identifier.emailLuk, KDK: hcm21000@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.authorityChan, V=rp00320en_HK
dc.identifier.authorityLuk, KDK=rp00333en_HK
dc.identifier.authorityKung, AWC=rp00368en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1210/jc.2007-2836en_HK
dc.identifier.pmid18697872-
dc.identifier.scopuseid_2-s2.0-57349109503en_HK
dc.identifier.hkuros192163en_US
dc.identifier.hkuros152560-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-57349109503&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume93en_HK
dc.identifier.issue11en_HK
dc.identifier.spage4448en_HK
dc.identifier.epage4455en_HK
dc.identifier.isiWOS:000260661900041-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCheung, CL=14520953400en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridChan, V=7202654865en_HK
dc.identifier.scopusauthoridPaterson, AD=7202360951en_HK
dc.identifier.scopusauthoridLuk, KDK=7201921573en_HK
dc.identifier.scopusauthoridKung, AWC=7102322339en_HK

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