Lack of association of a variable number of aspartic acid residues in the asporin gene with osteoarthritis susceptibility: case-control studies in Spanish Caucasians

Current concepts in osteoarthritis (OA) imply an imbalance of cartilage anabolic and catabolic processes in response to mechanical stress with the participation of inflammatory mediators [1]. Recent investigation has also shown that genetic factors account for a substantial portion of OA etiology [2,3]. These two considerations contribute to the interest of a recent report showing that a variant of asporin (ASPN) is a susceptibility factor for OA [4]. This association points to a defect in the anabolic side of cartilage homeostasis, identifies ASPN and transforming growth factor beta as important molecular players in this process, and suggests that regulatory genetic variants are important in OA susceptibility [5,6].ASPN is a new member of the small leucin-rich proteoglycan subfamily of proteins [7,8] that is expressed at low levels in normal cartilage but that is notably increased in OA cartilage [4]. Variant ASPN proteins are due to a microsatellite in the ASPN coding sequence that determines a variable number of aspartic acid (D) residues in the amino terminal region. The D14 allele is associated with increased OA susceptibility in the Japanese (odds ratio = 1.66–2.49, depending on the cohort) [4] due to its strong inhibition of the cartilage anabolic effects induced by transforming growth factor beta [4]. Given the significance of these results, we explored the ASPN effect in Spanish patients with severe knee or hip OA or with hand OA, but we did not find association. This result is similar to findings in UK Caucasians [9] and in the Greek population [10], and together the observations indicate that the ASPN microsatellite does not have a significant effect on OA susceptibility in European Caucasians.Patients were selected from consecutive patients undergoing total hip replacement (THR) or total knee replacement (TKR) and patients complaining of hand OA that were followed in the Rheumatology Unit. THR and TKR patients were included only if surgery has been perfo