Linkage of osteoporosis to chromosome 20p12 and association to BMP2

To access full text version of this article. Please click on the hyperlink "Full Text" at the bottom of this page Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, hav...

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Bibliographic Details
Published in:PLoS Biology
Main 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
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science 2007
Subjects:
Bone Density
Bone Morphogenetic Proteins
Chromosome Mapping
Chromosomes
Human
Pair 20
Iceland
Linkage (Genetics)
Mutation
Missense
Osteoporosis
Polymorphism
Genetic
Transforming Growth Factor beta
Variation (Genetics)
Online Access:http://hdl.handle.net/2336/13860
https://doi.org/10.1371/journal.pbio.0000069
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Summary:To access full text version of this article. Please click on the hyperlink "Full Text" at the bottom of this page 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.

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