The Mitochondrial Genome Influences the Risk of Incident Knee OA. DATA from the Osteoarthritis Initiative

Angel Soto-Hermida¹, Ignacio Rego-Pérez¹, Juan Fernández-Tajes¹, Mercedes Fernandez Moreno¹, María Eugenia Vázquez-Mosquera¹, Estefanía Cortés-Pereira¹, Sonia Pértega-Díaz², Natividad Oreiro-Villar¹, Carlos Fernandez-Lopez¹ and Francisco J. Blanco Garcia¹, ¹Servicio de Reumatología. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain, ²Unidad de Epidemiología Clínica y Bioestadística. Instituto de Investigación Biomédica de A Coruña (INIBIC). Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), A Coruña, Spain

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Genome, mitochondria and risk, OA

Session Information

Title: Genetics, Genomics and Proteomics II

Session Type: Abstract Submissions (ACR)

Background/Purpose

Previous studies by our group showed a significant influence of the mtDNA haplogroups on both radiographic progression and cartilage integrity of knee OA patients from the Osteoarthritis Initiative (OAI). The aim of this study is to analyze the influence of the mitochondrial variants on the risk of incident knee OA in patients with pre-radiographic OA of the OAI.

Methods

We assessed the mtDNA haplogroups in 2374 Caucasian samples of the OAI to analyze their influence on incident knee OA. Incidence of knee OA was defined as a KL score <2 at baseline and a KL≥2 at 4 years follow-up of the same knee. We also included individuals with unilateral KOA, since they were at risk of developing incident OA at the other knee. Statistical analyses included chi-square contingency tables and logistic regression models considering age, gender, body mass index (BMI), contralateral knee OA and mtDNA variants as variables of interest. Further, the area under the receiving operative characteristic (ROC) curve (AUC) of the model was also calculated.

Results

After 4 years of follow-up, a total of 214 patients developed incident knee OA, meanwhile 1323 did not. The rest of patients (n=837) had a KL score≥2 at baseline in both knees, therefore did not meet the selection criteria and were subsequently excluded from further analyses. Patients belonging to mtDNA cluster HV were significantly overrepresented in the incident knee OA group (OR=1.395; CI=1.044-1.8636; p=0.024) meanwhile patients in cluster TJ were less represented in the incident group (OR=0.692; CI=0.466-1.026;p=0.065). The logistic regression model showed that female gender (p<0.001), higher BMI (p<0.001) and contralateral knee OA (p<0.001) were risk factors to develop incident OA; additionally, OA patients in cluster HV were at higher risk for incident knee OA than patients in cluster TJ (p=0.016). The AUC of this regression model was 0.707

Conclusion

The mitochondrial genome contributes to the development of incident knee OA. The assignment of the mtDNA haplogroups could be used as complementary genetic biomarkers to predict the risk of incident knee OA.

Disclosure:

A. Soto-Hermida,
None;

I. Rego-Pérez,
None;

J. Fernández-Tajes,
None;

M. Fernandez Moreno,
None;

M. E. Vázquez-Mosquera,
None;

E. Cortés-Pereira,
None;

S. Pértega-Díaz,
None;

N. Oreiro-Villar,
None;

C. Fernandez-Lopez,
None;

F. J. Blanco Garcia,
None.

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