Mitochondrial DNA haplogroups and serum levels of proteolytic enzymes in patients with osteoarthritis

Ann Rheum Dis. 2011 Apr;70(4):646-52. doi: 10.1136/ard.2010.133637. Epub 2010 Dec 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Case-Control Studies
  • DNA, Mitochondrial / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Male
  • Matrix Metalloproteinase 13 / blood
  • Matrix Metalloproteinase 3 / blood
  • Middle Aged
  • Osteoarthritis, Hip / enzymology
  • Osteoarthritis, Hip / genetics*
  • Osteoarthritis, Knee / enzymology
  • Osteoarthritis, Knee / genetics*
  • Peptide Hydrolases / blood*

Substances

  • Biomarkers
  • DNA, Mitochondrial
  • Peptide Hydrolases
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3