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Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis

Lookup NU author(s): Professor John LoughlinORCiD



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.

Publication metadata

Author(s): Wilkins JM, Southam L, Mustafa Z, Chapman K, Loughlin J

Publication type: Article

Publication status: Published

Journal: BMC Medical Genetics

Year: 2009

Volume: 10

Pages: 141

Date deposited: 17/02/2010

ISSN (electronic): 1471-2350

Publisher: BioMed Central Ltd.


DOI: 10.1186/1471-2350-10-141


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Funder referenceFunder name
Marshall Aid Commemoration Commission
16239Arthritis Research Campaign
237Research into Ageing