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Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis
BACKGROUND: In a previous study carried out by our group, the genotyping of 36 microsatellite markers from within a narrow interval of chromosome 6p12.3-q13 generated evidence for linkage and for association to female hip osteoarthritis (OA), with the most compelling association found for a marker w...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807860/ https://www.ncbi.nlm.nih.gov/pubmed/20021689 http://dx.doi.org/10.1186/1471-2350-10-141 |
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author | Wilkins, James M Southam, Lorraine Mustafa, Zehra Chapman, Kay Loughlin, John |
author_facet | Wilkins, James M Southam, Lorraine Mustafa, Zehra Chapman, Kay Loughlin, John |
author_sort | Wilkins, James M |
collection | PubMed |
description | BACKGROUND: In a previous study carried out by our group, the genotyping of 36 microsatellite markers from within a narrow interval of chromosome 6p12.3-q13 generated evidence for linkage and for association to female hip osteoarthritis (OA), with the most compelling association found for a marker within intron 1 of the bone morphogenetic protein 5 gene (BMP5). In this study, we aimed to further categorize the association of variants within intron 1 of BMP5 with OA through an expanded genetic association study of the intron and subsequent functional analysis of associated polymorphisms. METHODS: We genotyped 18 common polymorphisms including 8 microsatellites and 9 single nucleotide polymorphisms (SNPs) and 1 insertion/deletion (INDEL) from within highly conserved regions between human and mouse within intron 1 of BMP5. These markers were then tested for association to OA by a two-stage approach in which the polymorphisms were initially genotyped in a case-control cohort comprising 361 individuals with associated polymorphisms (P ≤ 0.05) then genotyped in a second case-control cohort comprising 1185 individuals. RESULTS: Two BMP5 intron 1 polymorphisms demonstrated association in the combined case-control cohort of 1546 individuals (765 cases and 781 controls): microsatellite D6S1276 (P = 0.018) and SNP rs921126 (P = 0.013). Functional analyses in osteoblastic, chondrocytic, and adipocytic cell lines indicated that allelic variants of D6S1276 have significant effects on the transcriptional activity of the BMP5 promoter in vitro. CONCLUSION: Variability in gene expression of BMP5 may be an important contributor to OA genetic susceptibility. |
format | Text |
id | pubmed-2807860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28078602010-01-19 Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis Wilkins, James M Southam, Lorraine Mustafa, Zehra Chapman, Kay Loughlin, John BMC Med Genet Research article BACKGROUND: In a previous study carried out by our group, the genotyping of 36 microsatellite markers from within a narrow interval of chromosome 6p12.3-q13 generated evidence for linkage and for association to female hip osteoarthritis (OA), with the most compelling association found for a marker within intron 1 of the bone morphogenetic protein 5 gene (BMP5). In this study, we aimed to further categorize the association of variants within intron 1 of BMP5 with OA through an expanded genetic association study of the intron and subsequent functional analysis of associated polymorphisms. METHODS: We genotyped 18 common polymorphisms including 8 microsatellites and 9 single nucleotide polymorphisms (SNPs) and 1 insertion/deletion (INDEL) from within highly conserved regions between human and mouse within intron 1 of BMP5. These markers were then tested for association to OA by a two-stage approach in which the polymorphisms were initially genotyped in a case-control cohort comprising 361 individuals with associated polymorphisms (P ≤ 0.05) then genotyped in a second case-control cohort comprising 1185 individuals. RESULTS: Two BMP5 intron 1 polymorphisms demonstrated association in the combined case-control cohort of 1546 individuals (765 cases and 781 controls): microsatellite D6S1276 (P = 0.018) and SNP rs921126 (P = 0.013). Functional analyses in osteoblastic, chondrocytic, and adipocytic cell lines indicated that allelic variants of D6S1276 have significant effects on the transcriptional activity of the BMP5 promoter in vitro. CONCLUSION: Variability in gene expression of BMP5 may be an important contributor to OA genetic susceptibility. BioMed Central 2009-12-19 /pmc/articles/PMC2807860/ /pubmed/20021689 http://dx.doi.org/10.1186/1471-2350-10-141 Text en Copyright ©2009 Wilkins et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research article Wilkins, James M Southam, Lorraine Mustafa, Zehra Chapman, Kay Loughlin, John Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis |
title | Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis |
title_full | Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis |
title_fullStr | Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis |
title_full_unstemmed | Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis |
title_short | Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis |
title_sort | association of a functional microsatellite within intron 1 of the bmp5 gene with susceptibility to osteoarthritis |
topic | Research article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807860/ https://www.ncbi.nlm.nih.gov/pubmed/20021689 http://dx.doi.org/10.1186/1471-2350-10-141 |
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