Objective: The hallmark in osteoarthritis (OA) is the loss of proteoglycans (PGs) in articular cartilage (AC). Xylosyltransferase I (XT-I) catalyzes the transfer of xylose to serine residues in the core protein and initiates the biosynthesis of PGs in AC. The XYLT-II gene encodes a highly homologous protein but its biological function is not yet known. Here we investigate for the first time genetic variations in the XYLT-genes and serum XT-I activities and their implication in OA. Methods: Denaturing high-performance liquid chromatography (DHPLC) was used for the screening of the XYLT-genes in 49 OA patients. For a detailed characterization of XT-I amino acid exchanges we performed recombinant expression of XT-I mutants in insect cells. Furthermore, the XT activity was measured in the patients' serum. Results: The variation c.1569C > T (XYLT-II) occurs with a significantly higher frequency in younger OA patients in comparison with the older ones (P < 0.001) and the controls (P < 0.02). Furthermore, significantly higher serum XT activities were found in patients with a long disease duration of OA (P < 0.04). The recombinant XT-I mutants p.P385L and p.I552S had reduced enzymatic activity (85% and 74%) compared with the wildtype (wt). Conclusions: Our findings indicate a correlation of the c.1569 T-allele in XYLT-II with an earlier manifestation of OA and that the serum XT activity is a potential biochemical marker for staging and monitoring the progression of AC damage in OA. Comparison of XT-I activity in mutant enzymes in vivo and in vitro revealed that heterozygous mutations are not involved in OA. © 2005 OsteoArthritis Research Society International.
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