Association of a functional microsatellite within intron 1 of the <it>BMP5 </it>gene with susceptibility to osteoarthritis

• Main Authors: Chapman Kay (Author), Mustafa Zehra (Author), Southam Lorraine (Author), Wilkins James M (Author), Loughlin John (Author)
• Format: Book
• Published: BMC, 2009-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/1471-2350-10-141; 1471-2350
• Keywords: Internal medicine; RC31-1245; Genetics; QH426-470
• Source: BMC Medical Genetics, Vol 10, Iss 1, p 141 (2009)

<p>Abstract</p> <p>Background</p> <p>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 (<it>BMP5</it>). In this study, we aimed to further categorize the association of variants within intron 1 of <it>BMP5 </it>with OA through an expanded genetic association study of the intron and subsequent functional analysis of associated polymorphisms.</p> <p>Methods</p> <p>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 <it>BMP5</it>. 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 (<it>P </it>≤ 0.05) then genotyped in a second case-control cohort comprising 1185 individuals.</p> <p>Results</p> <p>Two <it>BMP5 </it>intron 1 polymorphisms demonstrated association in the combined case-control cohort of 1546 individuals (765 cases and 781 controls): microsatellite D6S1276 (<it>P </it>= 0.018) and SNP rs921126 (<it>P </it>= 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 <it>BMP5 </it>promoter <it>in vitro</it>.</p> <p>Conclusion</p> <p>Variability in gene expression of <it>BMP5 </it>may be an important contributor to OA genetic susceptibility.</p>