Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


mtDNA Haplogroups Define Two Phenotypes of Osteoarthritis (OA).

Rego-Perez4,  Ignacio, Fernandez-Moreno5,  Mercedes, Deberg1,  M., Pertega3,  Sonia, Fernandez-Lopez5,  Carlos, Oreiro5,  Natividad, Acasuso2,  Manuel

Bone and Cartilage Res. Unit. Univ. of Liege, Liege, Belgium
Centro de Salud Matogrande - SERGAS, A Coruña, Spain
Epidemiology Unit. INIBIC-Complejo Hosp. Univ. A Coruna, A Coruna, Spain
Osteoarticular and Aging Res. Lab. Rheumatology Div, INIBIC-Complejo Hosp, Univ. A Coruña, Coruña, Spain
Osteoarticular and Aging Res. Lab. Rheumatology Div, INIBIC-Complejo Hosp, Univ. A Coruña, A Coruña, Spain

Background:

Recent findings evidence that mitochondria mediate in the pathogenesis of the osteoarthritis (OA). Biomarkers are a promising tool to detect patients with OA preferably in an early stage of the disease. In this work we aim to assess a mitochondria-related phenotype in patients with OA.

Methods:

We analyzed the determinations of serum levels of 12 OA-related biomarkers: MMP-1, MMP-3, MMP-13, MPO, Coll2-1 Coll2-1NO2, C2C, CPII, hyaluronic acid, YKL-40, COMP and cathepsin K, in 48 OA patients and 52 healthy controls carrying the haplogroups H and J, to perform logistic regression models and receiver operating characteristic (ROC) curves that permit us to predict diagnosis of OA. This models also included clinical variables such as gender, age and smoking status.

Results:

The MMP-13 was the only biomarker significantly increased in OA patients, when compared with healthy controls, in both mtDNA haplogroups H and J (p<0.001). Type II collagen biomarkers Coll2-1, Coll2-1NO2, Coll2 ratio, C2C, CPII and C2C:CPII ratio were significantly increased in OA patients that carry the mtDNA haplogroup H when compared with OA carriers of the mtDNA haplogroup J (p<0.01 in all cases). The logistic regression model for diagnosis for carriers of the mtDNA haplogroup H showed that those biomarkers significantly associated with OA were hyaluronic acid and C2C:CPII; the area under the curve (AUC) of the ROC curve for this model was 0.926 (95% CI=0.857–0.995) and the optimal probability cutoff for discriminate between OA and healthy controls was 0.269, with a sensitivity of 96%, a specificity of 78%, and a positive likelihood ratio of 4.3. For carriers of the mtDNA haplogroup J, the logistic regresion model for diagnosis showed that those biomarkers significantly associated with OA were MMP-13, MMP-3 and C2C; the AUC for this model was 0.880 (95% CI=0.782–0.978), and the optimal probability cutoff for discriminate between OA patients and healthy controls was 0.271, with a sensitivity of 96%, a specificity of 68%, and a positive likelihood ratio of 3.

Conclusions:

MMP-13 appears to be a good candidate biomarker for diagnosing OA. Some of the OA-related biomarkers clearly show a different profile depending on the mtDNA haplogroup. This permitted us to perform two models of haplogroup-based diagnoses of OA.

To cite this abstract, please use the following information:
Rego-Perez, Ignacio, Fernandez-Moreno, Mercedes, Deberg, M., Pertega, Sonia, Fernandez-Lopez, Carlos, Oreiro, Natividad, et al; mtDNA Haplogroups Define Two Phenotypes of Osteoarthritis (OA). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :835
DOI: 10.1002/art.28603

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