Mitochondrial DNA haplogroups: role in the prevalence and severity of knee osteoarthritis

Arthritis Rheum. 2008 Aug;58(8):2387-96. doi: 10.1002/art.23659.

Abstract

Objective: Some studies indicate that the mitochondrion is implicated in osteoarthritis (OA). To test the hypothesis that mitochondrial DNA (mtDNA) haplogroups contribute to the prevalence and severity of knee OA, we analyzed the European mtDNA haplogroups in a Spanish population of patients with knee OA and healthy control subjects.

Methods: We combined the single-base extension assay with the polymerase chain reaction-restriction fragment length polymorphism technique to obtain the different single-nucleotide polymorphisms that characterize the European haplogroups in 457 patients with knee OA and 262 radiologic controls. Knee OA radiographs had previously been classified as grades 1-4 according to Kellgren/Lawrence (K/L) scoring system.

Results: Individuals carrying haplogroup J showed a significantly decreased risk of knee OA (odds ratio [OR] 0.460 [95% confidence interval (95% CI) 0.282-0.748], P = 0.002). In terms of K/L scores, patients carrying haplogroup J had a less severe progression of knee OA (OR 0.351 [95% CI 0.156-0.787], P = 0.012), while those carrying haplogroup U had a more severe progression (OR 1.788 [95% CI 1.094-2.922], P = 0.025).

Conclusion: People carrying haplogroup J may be at a lower risk of developing knee OA, and those carrying this haplogroup in whom knee OA does not develop may have a less severe progression of the disease. Patients with knee OA carrying haplogroup U may have a more severe progression of the disease. These results indicate that mtDNA haplogroups contribute to the pathogenesis of OA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • DNA, Mitochondrial / genetics*
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Haplotypes / genetics*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Osteoarthritis, Knee / ethnology
  • Osteoarthritis, Knee / genetics*
  • Osteoarthritis, Knee / physiopathology
  • Polymorphism, Single Nucleotide / genetics*
  • Prevalence
  • Severity of Illness Index
  • Spain

Substances

  • DNA, Mitochondrial