Objective To analyse the influence of mitochondrial DNA haplogroups, as well as the radiographic grade, on serum levels of proteolytic enzymes in patients with osteoarthritis (OA).
Methods Serum levels of metalloproteinase-1 (MMP-1), MMP-3, MMP-13, myeloperoxidase and cathepsin K were analysed in 73 patients with OA and 77 healthy controls carrying the haplogroups J, U and H, by ELISA. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L) scoring from grade 0 to grade IV. Non-parametric and multiple regression analyses were performed to test the effects of clinical variables, including gender, age, smoking status, diagnosis, haplogroups and radiological K/L grade on serum levels of these enzymes.
Results A significant influence of the haplogroups on the serum levels of MMP-3 and MMP-13 was detected (p=0.027 and p=0.035, respectively). Patients with OA with haplogroup H showed higher serum levels of MMP-3 than healthy controls. Serum levels of MMP-13 were significantly higher in patients with OA (p<0.001), and carriers of the haplogroup J showed lower levels than H carriers. Besides, levels of MMP-13 were proportionally higher in radiological groups B (K/L grade II and III) and C (K/L grade IV) than in group A (K/L grade 0 and I) (p=0.005).
Conclusions This study shows that haplogroups have a significant influence on serum levels of MMP-3 and MMP-13. The influence of the haplogroups on serum levels of MMP-3 is clearly dependent on the diagnosis, whereas the influence of the haplogroups on serum levels of MMP-13 is independent of diagnosis.
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Funding This study was supported by grants from Secretaria I+D+I Xunta Galicia (PGIDIT06PXIC916175PN); Fundación Española de Reumatologia (programa GEN-SER) and from Fondo Investigación Sanitaria (CIBER- CB06/01/0040)-Spain, Fondo Investigacion Sanitaria-PI 08/2028 Ministerio Ciencia en Innovacion PLE2009-0144, with participation of fundus from FEDER (European Community). IR-P was supported by Contrato de Apoyo a la Investigación-Fondo Investigación Sanitaria (CA06/01102).
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the ethical committee of the Galician Health Administration.
Provenance and peer review Not commissioned; externally peer reviewed.