Osteoarthritis Research Today is a free monthly online journal that collates and summarizes the latest research about Osteoarthritis, including details on treatment, symptoms, causes, medication.

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

Wilkins JM, Southam L, Mustafa Z, Chapman K, Loughlin J

University of Oxford, Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford, OX3 7LD, UK. james_wilkins@hms.harvard.edu

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 < or = 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.

Published 19 January 2010 in BMC Med Genet, 10: 141.
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