title: Mitochondrial haplogroups define two phenotypes of osteoarthritis.
abstract: OBJECTIVE
  To assess a mitochondrion-related phenotype in patients with osteoarthritis (OA).
  
  
  METHODS
  Serum levels of the following OA-related biomarkers: matrix metalloproteinase-1 (MMP-1); MMP-3; MMP-13; myeloperoxidase (MPO); a peptide of the alpha-helical region of type II collagen, Coll2-1, and its nitrated form Coll2-1NO(2); a C-terminal neoepitope generated by the collagenase-mediated cleavage of collagen type II triple helix, C2C; the C-propeptide of collagen type II, CPII; hyaluronic acid (HA); human cartilage glycoprotein 39, YKL-40; cartilage oligomeric matrix protein; and cathepsin K were analyzed in 48 OA patients and 52 healthy controls carrying the haplogroups H and J. Logistic regression models and receiver operating characteristic (ROC) curves were performed to predict the onset of OA.
  
  
  RESULTS
  MMP-13 was the only biomarker significantly increased in OA patients compared to healthy controls in both haplogroups H and J. The collagen type II biomarkers, Coll2-1, Coll2-1NO(2), the Coll2-1NO(2)/Coll2-1 ratio, C2C, CPII, and the C2C:CPII ratio were significantly increased in OA patients carrying haplogroup H compared to OA carriers of the haplogroup J. Two logistic regression models for diagnosis were constructed and adjusted for age, gender, and body mass index. For haplogroup H, the biomarkers significantly associated with OA were MMP-13 and Coll2-1; the area under the curve (AUC) of the ROC curve for this model was 0.952 (95% CI = 0.892-1.012). For haplogroup J, the only biomarker significantly associated with OA was MMP-13; the AUC for this model was 0.895 (95% CI = 0.801-0.989).
  
  
  CONCLUSIONS
  The mitochondrial DNA haplogroups are potential complementary candidates for biomarkers of OA; their genotyping in conjunction with the assessment of classical protein molecular markers is recommended.
authors.affiliation: Rheumatology Division, Genomic Lab Instituto de Investigación Biomédica-Hospital Universitario A Coruña A Coruña, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Fernández-Moreno
authors.forename: Angel
authors.initials: A
authors.lastname: Soto-Hermida
authors.forename: Natividad
authors.initials: N
authors.lastname: Oreiro
authors.forename: Sonia
authors.initials: S
authors.lastname: Pértega
authors.forename: Carlos
authors.initials: C
authors.lastname: Fenández-López
authors.forename: Ignacio
authors.initials: I
authors.lastname: Rego-Pérez
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco