Background/Purpose:

The Osteoarthritis Initiative (OAI) is a multicentre study focused on identifying and evaluating risk factors of knee osteoarthritis (OA). Previous studies carried out by our group showed the role of the mitochondrial DNA (mtDNA) haplogroups on the prevalence and severity of OA. The aim of this study is to replicate our previous findings about the influence of the mtDNA haplogroups on OA progression in the well characterized cohort of the OAI.

Methods:

We assigned the mtDNA haplogroups in 891 Caucasian samples of the progression subcohort of the OAI to analyse their influence on radiographic OA progression attending to: KL grade, joint space narrow (JSN), presence of osteophytes and subchondral sclerosis in media tibial compartment between baseline and visit 6 (48 months). The progression criteria for KL grade consisted in an increase of at least one (KL or OARSI) grade at any visit and any knee; for JSN if an increase in score by a grade ³ 0.5 of the OARSI scale at any visit and any knee occurred. Additionally, we also analysed the four-year change in radiographic medial joint space width (mJSW) at x=0.225 in (N=265) patients with baseline unilateral JSN in both JSN knees (OARSI atlas grade ≥ 1) and non-JSN knees (OARSI atlas grade < 1).

Appropriate statistical analyses adjusting by gender, age and body mass index (BMI) at baseline were carried out using SPSS software (v.19) and R software v2.10.0 (The R Foundation for Statistical Computing).

Results:

OA patients in the progression subcohort that carry the mtDNA haplogroup T showed the lowest significant cumulative probability of progression in terms of KL grade (Relative Risk (RR) = 0.490; 95% Confidence Interval (CI): 0.208 – 0.762; p < 0.05), osteophytes (RR = 0.490; 95% CI: 0.208 – 0.762; p < 0.05), subchondral esclerosis (RR = 0.490; 95% CI: 0.208 – 0.762; p < 0.05) and JSN (RR = 0.490; 95% CI: 0.208 – 0.762; p < 0.05) when compared with OA patients that carry the most common mtDNA haplogroup H.

Regarding to mJSW at x=0.225 in both knees of patients with unilateral JSN during the follow-up period of 48 months, the results obtained showed that carriers of the haplogroup T had a significant smaller decline in the mJSW at x=0.225 in non-JSN knees (p = 0.033). For JSN knees, though carriers of the haplogroup T showed the smallest decline too, the differences did not reach the statistical significance.

Conclusion:

This work strength the hypothesis that mitochondrial genome is a key factor in the progression of the OA disease. The early identification and classification of patients with haplogroup T and the most common haplogroup H would permit to carry out a more personalized follow-up of the disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-uncoupling-mtdna-haplogroup-t-associates-with-better-radiographic-progression-of-osteoarthritis-data-from-the-osteoarthritis-initiative-oai/