Mitochondrial DNA (mtDNA) haplogroups influence the progression of knee osteoarthritis: data from the Osteoarthritis Initiative (OAI)

Abstract

[Abstract] OBJECTIVE: To evaluate the influence of the mtDNA haplogroups on knee osteoarthritis progression in Osteoarthritis Initiative (OAI) participants through longitudinal data from radiographs and magnetic resonance imaging (MRI).

METHODS: Four-year knee osteoarthritis progression was analyzed as increase in Kellgren and Lawrence (KL) grade, in addition to increase in OARSI atlas grade for joint space narrowing (JSN), osteophytes and subchondral sclerosis in the tibia medial compartment of 891 Caucasian individuals from the progression subcohort. The influence of the haplogroups on the rate of structural progression was also assessed as the four-year change in minimum joint space width (mJSW in millimetres) in both knees of (n = 216) patients with baseline unilateral medial-tibiofemoral JSN. Quantitative cartilage measures from longitudinal MRI data were those related to cartilage thickness and volume with a 24 month follow-up period (n = 381).

RESULTS: During the four-year follow-up period, knee OA patients with the haplogroup T showed the lowest increase in KL grade (Hazard Risk [HR] = 0.499; 95% Confidence Interval [CI]: 0.261-0.819; p<0.05) as well as the lowest cumulative probability of progression for JSN (HR = 0.547; 95% CI: 0.280-0.900; p<0.05), osteophytes (HR = 0.573; 95% CI: 0.304-0.893; p<0.05) and subchondral sclerosis (HR = 0.549; 95% CI: 0.295-0.884; p<0.05). They also showed the lowest decline in mJSW (standardized response means (SRM) = -0.39; p = 0.037) in those knees without baseline medial JSN (no-JSN knees). Normalized cartilage volume loss was significantly lower in patients carrying the haplogroup T at medial tibia femoral (SRM = -0.33; p = 0.023) and central medial femoral (SRM = -0.27; p = 0.031) compartments. Cartilage thickness loss was significantly lower in carriers of haplogroup T at central medial tibia-femoral (SRM = -0.42; p = 0.011), medial tibia femoral (SRM = -0.32; p = 0.018), medial tibia anterior (SRM = +0.31; p = 0.013) and central medial femoral (SRM = -0.19; p = 0.013) compartments.

CONCLUSIONS: Mitochondrial genome seems to play a role in the progression of knee osteoarthritis. mtDNA variation could improve identification of patients predisposed to faster or severe progression of the disease.