骨关节炎是一种非常常见的关节退行性疾病。申请人团队的前期研究以及国外队列研究发现骨关节炎病人暴露于更高的心血管疾病风险中。然而，目前的研究多局限于骨关节炎与心血管疾病相关联的现象，尚缺乏有效的生物标记物用于评估骨关节炎病人的心血管疾病风险。研究表明软骨低聚合基质蛋白（Cartilage Oligomeric Matrix Protein， COMP）不仅深度参与了骨关节炎的病理生理过程，也能被血管平滑肌细胞和心肌细胞等合成，并参与了心血管疾病的病理生理进程。因此，申请人团队提出这样的科学假说：COMP参与介导了骨关节炎与心血管疾病的关联，可做为早期评估骨关节炎病人心血管疾病风险的潜在生物标记物；其水平受到部分相关基因多态性位点的调节。为了验证这一假说，我们将综合运用分子流行病学和分子生物学研究方法，从人群、细胞和分子水平，系统阐明在骨关节炎人群中COMP对于心血管疾病发生发展的

Osteoarthritis is a highly prevalent degenerative disease of the joint. According to our previous study and the results of several cohort studies, patients with osteoarthritis are subjected to increased risk of cardiovascular disease morbidity and mortality. However, current studies are limited to the phenomenon of the relationship between osteoarthritis and cardiovascular disease, and the biomarker for the evaluation of cardiovascular risk in osteoarthritic patients are urgently needed. Cartilage Oligomeric Matrix Protein (COMP) is thought to play an important role in the pathophysiology of both osteoarthritis and cardiovascular disease, for it is synthesized by cartilage cells as well as by vascular smooth muscle cells and cardiomyocytes. Therefore, we hypothesized that COMP mediates the relationship between osteoarthritis and cardiovascular disease, and servers as a biomarker for the risk of cardiovascular disease in osteoarthritic patients; the level of COMP is regulated by several single nucleotide polymorphisms. To test this hypothesis, we will make a comprehensive study by employing molecular epidemiological and biological methods, at the levels of population, cell and molecular, to systematically determinate the potential role of COMP in the risk of cardiovascular disease in patients with osteoarthritis.