Mitochondrial DNA haplogroups modulate the serum levels of biomarkers in patients with osteoarthritis

Ann Rheum Dis. 2010 May;69(5):910-7. doi: 10.1136/ard.2009.117416. Epub 2009 Nov 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Collagen Type II / blood
  • DNA, Mitochondrial / genetics*
  • Female
  • Haplotypes
  • Humans
  • Hyaluronic Acid / blood
  • Male
  • Middle Aged
  • Osteoarthritis, Hip / blood
  • Osteoarthritis, Hip / diagnostic imaging
  • Osteoarthritis, Hip / genetics*
  • Osteoarthritis, Knee / blood
  • Osteoarthritis, Knee / diagnostic imaging
  • Osteoarthritis, Knee / genetics*
  • Peptide Fragments / blood
  • Radiography
  • Retrospective Studies
  • Severity of Illness Index


  • Biomarkers
  • Collagen Type II
  • DNA, Mitochondrial
  • Peptide Fragments
  • collagen type II (108-116)
  • collagen type II (108-116), (NO2)Tyr(111)-
  • Hyaluronic Acid