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Article: The - 9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPα and FOXA1 binding is associated with osteoporosis

TitleThe - 9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPα and FOXA1 binding is associated with osteoporosis
Authors
KeywordsAssociation
Osteoporosis
Sclerostin
Issue Date2009
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/bone
Citation
Bone, 2009, v. 45 n. 2, p. 289-294 How to Cite?
AbstractAccumulating evidence shows that genes that cause monogenic diseases also contribute to similar complex disease in the general population. We sought to determine whether the allelic variation in seven monogenic bone disease genes (CLCN7, TCIRGI, SOST, CA2, CSTK, TGFB1 and SLC26A2) contributes to osteoporosis/bone mineral density (BMD) variation in the normal Chinese population. We conducted a gene-wide tag SNP-based association study in 1243 Chinese subjects with low BMD (Z-scores ≤ - 1.28, equivalent to the lowest 10% of the population) and high BMD (Z-score ≥ + 1.0). Twenty-two tag SNPs were selected and genotyped by using the high-throughput Sequenom genotyping platform. Allelic and haplotype association tests were conducted by Haploview and binary logistic regression analyses. The - 9247 polymorphism rs1230399 in the upstream regulatory region of the sclerostin gene showed significant genotypic/allelic associations with spine, femoral neck, trochanter and total hip BMD (P = 0.03-0.004). The T-allele of rs1230399 increased the risk of osteoporosis (OR = 1.52, P = 0.005). Computational analysis showed that rs1230399 is located at the core consensus recognition site of two cooperating transcription factors C/EBPα and FOXA1 that modulate estrogen receptor function. T → C polymorphism abolishes the binding of both C/EBPα and FOXA1 to the sclerostin gene. Our data suggest a mechanistic link between rs1230399 and BMD through estrogen ERα/FOXA1 signaling pathways driven by long-distance enhancers. © 2009 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/163257
ISSN
2015 Impact Factor: 3.736
2015 SCImago Journal Rankings: 1.752
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHuang, QYen_HK
dc.contributor.authorLi, GHYen_HK
dc.contributor.authorKung, AWCen_HK
dc.date.accessioned2012-09-05T05:29:13Z-
dc.date.available2012-09-05T05:29:13Z-
dc.date.issued2009en_HK
dc.identifier.citationBone, 2009, v. 45 n. 2, p. 289-294en_HK
dc.identifier.issn8756-3282en_HK
dc.identifier.urihttp://hdl.handle.net/10722/163257-
dc.description.abstractAccumulating evidence shows that genes that cause monogenic diseases also contribute to similar complex disease in the general population. We sought to determine whether the allelic variation in seven monogenic bone disease genes (CLCN7, TCIRGI, SOST, CA2, CSTK, TGFB1 and SLC26A2) contributes to osteoporosis/bone mineral density (BMD) variation in the normal Chinese population. We conducted a gene-wide tag SNP-based association study in 1243 Chinese subjects with low BMD (Z-scores ≤ - 1.28, equivalent to the lowest 10% of the population) and high BMD (Z-score ≥ + 1.0). Twenty-two tag SNPs were selected and genotyped by using the high-throughput Sequenom genotyping platform. Allelic and haplotype association tests were conducted by Haploview and binary logistic regression analyses. The - 9247 polymorphism rs1230399 in the upstream regulatory region of the sclerostin gene showed significant genotypic/allelic associations with spine, femoral neck, trochanter and total hip BMD (P = 0.03-0.004). The T-allele of rs1230399 increased the risk of osteoporosis (OR = 1.52, P = 0.005). Computational analysis showed that rs1230399 is located at the core consensus recognition site of two cooperating transcription factors C/EBPα and FOXA1 that modulate estrogen receptor function. T → C polymorphism abolishes the binding of both C/EBPα and FOXA1 to the sclerostin gene. Our data suggest a mechanistic link between rs1230399 and BMD through estrogen ERα/FOXA1 signaling pathways driven by long-distance enhancers. © 2009 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/boneen_HK
dc.relation.ispartofBoneen_HK
dc.rightsBone. Copyright © Elsevier Inc.-
dc.subjectAssociationen_HK
dc.subjectOsteoporosisen_HK
dc.subjectSclerostinen_HK
dc.subject.meshBone Morphogenetic Proteins - Geneticsen_US
dc.subject.meshCcaat-Enhancer-Binding Protein-Alpha - Metabolismen_US
dc.subject.meshComputational Biologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshGenetic Markers - Geneticsen_US
dc.subject.meshGenetic Predisposition To Diseaseen_US
dc.subject.meshHaplotypesen_US
dc.subject.meshHepatocyte Nuclear Factor 3-Alpha - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshOsteoporosis - Geneticsen_US
dc.subject.meshPolymorphism, Single Nucleotide - Geneticsen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshRegulatory Sequences, Nucleic Acid - Geneticsen_US
dc.titleThe - 9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPα and FOXA1 binding is associated with osteoporosisen_HK
dc.typeArticleen_HK
dc.identifier.emailHuang, QY: qyhuang@hotmail.comen_HK
dc.identifier.emailKung, AWC: awckung@hku.hken_HK
dc.identifier.authorityHuang, QY=rp00521en_HK
dc.identifier.authorityKung, AWC=rp00368en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.bone.2009.03.676en_HK
dc.identifier.pmid19371798-
dc.identifier.scopuseid_2-s2.0-67649651479en_HK
dc.identifier.hkuros155801-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67649651479&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume45en_HK
dc.identifier.issue2en_HK
dc.identifier.spage289en_HK
dc.identifier.epage294en_HK
dc.identifier.isiWOS:000268206300020-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHuang, QY=7403630787en_HK
dc.identifier.scopusauthoridLi, GHY=35080710200en_HK
dc.identifier.scopusauthoridKung, AWC=7102322339en_HK

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