Mitochondrial DNA (mtDNA) haplogroups and serum levels of anti-oxidant enzymes in patients with osteoarthritis

Carlos Fernandez-Lopez,Sonia Pertega,Francisco J Blanco,Mercedes Fernandez-Moreno,Angel Soto-Hermida,Natividad Oreiro,Ignacio Rego-Perez

doi:10.1186/1471-2474-12-264

Abstract

BackgroundOxidative stress play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. To prevent this, the chondrocytes possess a well-coordinated enzymatic antioxidant system. Besides, the mitochondrial DNA (mtDNA) haplogroups are associated with the OA disease. Thus, the main goal of this work is to assess the incidence of the mtDNA haplogroups on serum levels of two of the main antioxidant enzymes, Manganese Superoxide Dismutase (Mn-SOD or SOD2) and catalase, and to test the suitability of these two proteins for potential OA-related biomarkers.MethodsWe analyzed the serum levels of SOD2 and catalase in 73 OA patients and 77 healthy controls carrying the haplogroups J, U and H, by ELISA assay. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L) scoring from Grade 0 to Grade IV. Appropriate statistical analyses were performed to test the effects of clinical variables, including gender, body mass index (BMI), age, smoking status, diagnosis, haplogroups and radiologic K/L grade on serum levels of these enzymes.ResultsSerum levels of SOD2 appeared statistically increased in OA patients when compared with healthy controls (p < 0.001). Even in those OA patients with higher OA severity (K/L grade IV), the serum levels of this antioxidant enzyme appeared more significantly increased than in OA patients with lower K/L grade (p < 0.001). The mtDNA haplogroups showed an influence on serum levels of catalase (p = 0.054), being carriers of the mtDNA haplogroup J those who showed higher serum levels than non-J carriers (p = 0.057).ConclusionsThe increased levels of SOD2 in OA patients indicate an increased oxidative stress OA-related, therefore this antioxidant enzyme could be a suitable candidate biomarker for diagnosis of OA. Mitochondrial haplogroups significantly correlates with serum levels of catalase

Highlights

Oxidative stress play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria
The results showed that levels of SOD2 were significantly increased in OA patients (p < 0.001) (Table 1)
When we compared the three groups based on the Kellgren and Lawrence (K/ L) score, only SOD2 showed a significant trend towards proportionally higher serum levels in both groups B (K/ L grade II and III) and C (K/L grade IV) than in group

Summary

Introduction

Oxidative stress play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. The metabolic and structural changes that take place in the articular cartilage, OA-related molecular biomarkers are being developed with the aim of detecting the progression of OA with more reliability and sensitivity, preferably early in the disease process [2,3] Because of their greater sensitivity compared with radiographs, several molecular markers for bone, cartilage and synovial have been described as useful for the early identification of OA and of patients at high risk for progression, for monitoring disease progression, and for assessing therapeutic response [3,4,5,6]. These redox reactions, carried out by a series of protein complexes within mitochondria, release energy which is used to form ATP

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