Mitochondrial DNA haplogroups modulate the serum levels of biomarkers in patients with osteoarthritis
Mitochondrial DNA haplogroups modulate the serum levels of biomarkers in patients with osteoarthritis
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DOI：
10.1136/ard.2009.117416
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发表时间：
2010-05-01
影响因子：
27.4
通讯作者：
Blanco, F. J.
中科院分区：
文献类型：
--
作者：
Rego-Perez, I.;Fernandez-Moreno, M.;Blanco, F. J.
目的分析线粒体DNA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。方法血清软骨代谢分子生物标志物水平（II型胶原蛋白标志物：通过胶原酶介导的II型胶原三螺旋（C2C）、II型胶原使用ELISA分析了73例OA患者和77例健康对照者的胶原蛋白（Coll2 - 1及其硝化形式，Coll2 - 1NO（2））、II型前胶原（CPII））、滑膜代谢（透明质酸（HA））以及软骨和滑膜转换（软骨糖蛋白39（YKL-40））。所有参与者先前都进行了mtDNA单倍群J、U和H的基因分型。结果OA患者血清HA水平明显高于正常对照组（P < 0. 05），而正常对照组血清HA水平明显高于正常对照组（P < 0. 05）。而健康对照组的C2C和C2C/CPII比值显著较高。多元回归分析显示mtDNA单倍型群与血清典型II型胶原标志物水平之间存在相关性。线粒体DNA单倍群H的携带者有较高的水平，而线粒体DNA单倍群J的携带者显示较低的水平。mtDNA单倍型群与血清分子标记物的诊断及放射学K/L分级之间也存在显著的交互作用。结果表明，mtDNA单倍型群与OA相关的分子标记物的血清水平显着相互作用，这表明它们作为这些分子标记物的互补检测的可能性。
Objective To analyse the influence of mitochondrial DNA (mtDNA) haplogroups on serum levels of molecular biomarkers in patients with osteoarthritis (OA).Methods 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.Results 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.Conclusion 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.