Genetic association analysis of BMP5 as a potential osteoarthritis susceptibility gene

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Abstract
Sir, A number of twin‐pair and sibling risk studies have revealed a major genetic component to primary osteoarthritis (OA), which best fits into the oligogenic multifactorial class of human diseases [1]. We have linkage mapped an OA susceptibility locus to an 11.4 cM interval at chromosome 6p12.3‐q13 in a cohort of 146 affected female sibling pair families ascertained by total hip replacement (female‐THR families) for primary OA, with a maximum multipoint LOD score of 4.0 [2]. This interval encompasses the candidate gene BMP5 (6p12.1), which encodes for bone morphogenetic protein 5. BMPs are bone‐derived factors that can induce new bone formation. BMP1 is a protease involved in the maturation of fibrillar collagens, whilst the remaining BMPs, including BMP5, are secreted molecules belonging to the transforming growth factor‐β family of growth and differentiation factors [3]. The normal development and repair of the synovial joint is influenced by the activity of BMPs, so it is reasonable to speculate that variation in the activity or action of these molecules could influence the development of arthritic phenotypes [4, 5]. Using genetic association analysis, we have tested BMP5 as the chromosome 6 OA susceptibility gene.

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