Osteoarticular and Aging Research Laboratory, Rheumatology Division, Complejo Hospitalario Universitario A Coruña, 15006-A Coruña, Spain.
Ann Rheum Dis. 2010 May;69(5):910-7. doi: 10.1136/ard.2009.117416. Epub 2009 Nov 23.
To analyse the influence of mitochondrial DNA (mtDNA) haplogroups on serum levels of molecular biomarkers in patients with osteoarthritis (OA).
Serum levels of molecular biomarkers of cartilage metabolism (collagen type II markers: C-terminal neoepitope generated by the collagenase-mediated cleavage of collagen type II triple helix (C2C), collagen type II (Coll2-1, and its nitrated form, Coll2-1NO(2)), procollagen type II (CPII)), synovial metabolism (hyaluronic acid (HA)) and cartilage and synovial turnover (cartilage glycoprotein 39 (YKL-40)) were analysed in 73 patients with OA and 77 healthy controls using ELISAs. All participants had been previously genotyped for the mtDNA haplogroups J, U and H. Non-parametric and multivariate analysis were performed to test the effects of the clinical variables, including gender, age, smoking status, diagnosis, mtDNA haplogroups and radiological Kellgren and Lawrence (K/L) grade on the serum levels of the molecular markers.
Non-parametric analysis found increased serum levels of HA in patients with OA, while the values for C2C and the C2C/CPII ratio were significantly higher in the healthy controls. A multiple regression analysis showed a relationship between the mtDNA haplogroups and serum levels of the typical collagen type II markers. Carriers of the mtDNA haplogroup H had higher levels while carriers of the mtDNA haplogroup J showed lower levels. Statistically significant interactions between mtDNA haplogroups and diagnosis and between mtDNA haplogroups and radiological K/L grade in the serum levels of molecular markers were also found.
A new role for mtDNA haplogroups emerges from this work. The results suggest that the mtDNA haplogroups interact significantly with the serum levels of OA-related molecular markers, suggesting the possibility of their use as a complementary assay with these molecular markers.
分析线粒体 DNA（mtDNA）单倍群对骨关节炎（OA）患者血清分子生物标志物水平的影响。
采用 ELISA 法检测 73 例 OA 患者和 77 例健康对照者血清软骨代谢标志物（胶原 II 标志物：胶原 II 三螺旋酶解产生的 C 末端新表位（C2C）、胶原 II（Coll2-1）及其硝化形式 Coll2-1NO(2)）、前胶原 II（CPII））、滑膜代谢物（透明质酸（HA））和软骨及滑膜转换物（软骨糖蛋白 39（YKL-40））的水平。所有参与者均已进行 mtDNA 单倍群 J、U 和 H 的基因分型。采用非参数和多变量分析，检测临床变量（包括性别、年龄、吸烟状态、诊断、mtDNA 单倍群和放射学 Kellgren 和 Lawrence（K/L）分级）对分子标志物血清水平的影响。
非参数分析发现 OA 患者血清 HA 水平升高，而健康对照组 C2C 及 C2C/CPII 比值显著升高。多元回归分析显示 mtDNA 单倍群与典型胶原 II 标志物血清水平之间存在相关性。携带 mtDNA 单倍群 H 的患者水平较高，而携带 mtDNA 单倍群 J 的患者水平较低。还发现 mtDNA 单倍群与诊断以及 mtDNA 单倍群与放射学 K/L 分级之间在分子标志物血清水平上存在显著的相互作用。
本研究发现 mtDNA 单倍群具有新的作用。结果表明，mtDNA 单倍群与 OA 相关分子标志物的血清水平显著相互作用，提示它们有可能作为这些分子标志物的补充检测方法。
