2.50
Hdl Handle:
http://hdl.handle.net/2336/13860
Title:
Linkage of osteoporosis to chromosome 20p12 and association to BMP2
Authors:
Styrkarsdottir, Unnur; Cazier, Jean-Baptiste; Kong, Augustine; Rolfsson, Ottar; Larsen, Helene; Bjarnadottir, Emma; Johannsdottir, Vala D; Sigurdardottir, Margret S; Bagger, Yu; Christiansen, Claus; Reynisdottir, Inga; Grant, Struan F A; Jonasson, Kristjan; Frigge, Michael L; Gulcher, Jeffrey R; Sigurdsson, Gunnar; Stefansson, Kari
Citation:
PLoS Biol. 2003, 1(3):E69
Issue Date:
1-Dec-2003
Abstract:
Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 x 10(-7)), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes.
Description:
To access full text version of this article. Please click on the hyperlink "Full Text" at the bottom of this page
Additional Links:
http://dx.doi.org/10.1371/journal.pbio.0000069

Full metadata record

DC FieldValue Language
dc.contributor.authorStyrkarsdottir, Unnur-
dc.contributor.authorCazier, Jean-Baptiste-
dc.contributor.authorKong, Augustine-
dc.contributor.authorRolfsson, Ottar-
dc.contributor.authorLarsen, Helene-
dc.contributor.authorBjarnadottir, Emma-
dc.contributor.authorJohannsdottir, Vala D-
dc.contributor.authorSigurdardottir, Margret S-
dc.contributor.authorBagger, Yu-
dc.contributor.authorChristiansen, Claus-
dc.contributor.authorReynisdottir, Inga-
dc.contributor.authorGrant, Struan F A-
dc.contributor.authorJonasson, Kristjan-
dc.contributor.authorFrigge, Michael L-
dc.contributor.authorGulcher, Jeffrey R-
dc.contributor.authorSigurdsson, Gunnar-
dc.contributor.authorStefansson, Kari-
dc.date.accessioned2007-09-28T15:51:36Z-
dc.date.available2007-09-28T15:51:36Z-
dc.date.issued2003-12-01-
dc.date.submitted2007-09-28-
dc.identifier.citationPLoS Biol. 2003, 1(3):E69en
dc.identifier.issn1545-7885-
dc.identifier.pmid14691541-
dc.identifier.doi10.1371/journal.pbio.0000069-
dc.identifier.urihttp://hdl.handle.net/2336/13860-
dc.descriptionTo access full text version of this article. Please click on the hyperlink "Full Text" at the bottom of this pageen
dc.description.abstractOsteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 x 10(-7)), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes.en
dc.format.extent441899 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.relation.urlhttp://dx.doi.org/10.1371/journal.pbio.0000069en
dc.subject.meshBone Densityen
dc.subject.meshBone Morphogenetic Proteinsen
dc.subject.meshChromosome Mappingen
dc.subject.meshChromosomes, Human, Pair 20en
dc.subject.meshIcelanden
dc.subject.meshLinkage (Genetics)en
dc.subject.meshMutation, Missenseen
dc.subject.meshOsteoporosisen
dc.subject.meshPolymorphism, Geneticen
dc.subject.meshTransforming Growth Factor betaen
dc.subject.meshVariation (Genetics)en
dc.titleLinkage of osteoporosis to chromosome 20p12 and association to BMP2en
dc.typeArticleen
dc.identifier.journalPLoS biologyen
dc.format.digYES-

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