SAT0005 A Meta-Analysis and A Functional Study with Transmitochondrial Cybrids Confirm The Role of The Mtdna Haplogroups in The Development of Incident Knee Osteoarthritis. Data from Check and Oai

Background In the last years the study of the mitochondria in the context of osteoarthritis (OA) attracted much attention. In the present work we aim to analyze the role of the mtDNA haplogroups in the development of incident knee OA in well-characterized study cohorts Objectives To analyze the influence of the mtDNA haplogroups in the rate of incident knee OA in the prospective cohorts of CHECK and OAI and to perform functional analysis with transmitochondrial cybrids to explore the consequences of the mitochondrial background in the pathogenesis of Osteoarthritis Methods The influence of the haplogroups in the development of incident knee OA at eight years in 2579 subjects from the Osteoarthritis Initiative (OAI) and 635 subjects from the Cohort hip and Cohort knee (CHECK) was assessed. A subsequent meta-analysis was conducted to strengthen the association of these individual studies. Transmitochondrial cybrids carrying the haplogroups J and H were constructed to study the influence of the mitochondrial background in different OA-related features. Results The haplogroup J significantly associates with a decreased risk of incident knee OA in subjects from the OAI (HR=0.680;95%CI=0.470–0.968;p Compared with the haplogroup H, haplogroup J shows a lower free radical production, specially peroxide/peroxynitrite (52.51±11.34 vs 41.26±7.48;p Conclusions The haplogroup J reduces the risk of incident knee OA. This mitochondrial variant constitute a protective phenotype against the development of OA, emerging as a powerful OA biomarker and even leading to the consideration of the mitochondrion as a potential therapeutic target in OA Acknowledgement We9d like to acknowledge to the participants of CHECK and OAI cohorts Disclosure of Interest None declared