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dc.contributor.authorFernández-Moreno, Mercedes
dc.contributor.authorSoto-Hermida, Ángel
dc.contributor.authorVázquez-Mosquera, María E.
dc.contributor.authorCortés-Pereira, Estefanía
dc.contributor.authorRelaño, Sara
dc.contributor.authorHermida Gómez, Tamara
dc.contributor.authorPértega-Díaz, Sonia
dc.contributor.authorOreiro, Natividad
dc.contributor.authorFernández-López, Carlos
dc.contributor.authorGaresse, Rafael
dc.contributor.authorBlanco García, Francisco J
dc.contributor.authorRego-Pérez, Ignacio
dc.date.accessioned2020-03-23T11:23:58Z
dc.date.available2020-03-23T11:23:58Z
dc.date.issued2016-12-05
dc.identifier.citationFernández-Moreno M, Soto-Hermida A, Vázquez-Mosquera ME, Cortés-Pereira E, Relaño S, Hermida-Gómez T, et al. Mitochondrial DNA haplogroups influence the risk of incident knee osteoarthritis in OAI and CHECK cohorts: a meta-analysis and functional study. Ann Rheum Dis. 2017;76(6): 1114-1122es_ES
dc.identifier.issn0003-4967
dc.identifier.urihttp://hdl.handle.net/2183/25210
dc.descriptionExtended reportes_ES
dc.description.abstract[Abstract] Objective To evaluate the influence of the mitochondrial DNA (mtDNA) haplogroups in the risk of incident knee osteoarthritis (OA) and to explain the functional consequences of this association to identify potential diagnostic biomarkers and therapeutic targets. Methods Two prospective cohorts contributed participants. The osteoarthritis initiative (OAI) included 2579 subjects of the incidence subcohort, and the cohort hip and cohort knee (CHECK) included 635, both with 8-year follow-up. The analysis included the association of mtDNA haplogroups with the rate of incident knee OA in subjects from both cohorts followed by a subsequent meta-analysis. Transmitochondrial cybrids harbouring haplogroup J or H were constructed to detect differences between them in relation to physiological features including specific mitochondrial metabolic parameters, reactive oxygen species production, oxidative stress and apoptosis. Results Compared with H, the haplogroup J associates with decreased risk of incident knee OA in subjects from OAI (HR=0.680; 95% CI 0.470 to 0.968; p<0.05) and CHECK (HR=0.728; 95% CI 0.469 to 0.998; p<0.05). The subsequent meta-analysis including 3214 cases showed that the haplogroup J associates with a lower risk of incident knee OA (HR=0.702; 95% CI 0.541 to 0.912; p=0.008). J cybrids show a lower free radical production, higher cell survival under oxidative stress conditions, lower grade of apoptosis as well as lower expression of the mitochondrially related pro-apoptotic gene BCL2 binding component 3 (BBC3). In addition, J cybrids also show a lower mitochondrial respiration and glycolysis leading to decreased ATP production. Conclusions The physiological effects of the haplogroup J are beneficial to have a lower rate of incident knee OA over time. Potential drugs to treat OA could focus on emulating the mitochondrial behaviour of this haplogroup.es_ES
dc.description.sponsorshipInstituto de Salud Carlos III; CIBERCB06/01/0040-Spaines_ES
dc.description.sponsorshipInstituto de Salud Carlos III; RETIC-RIER-RD12/0009/0018es_ES
dc.description.sponsorshipInstituto de Salud Carlos III; PI14/01254es_ES
dc.description.sponsorshipInstituto de Salud Carlos III; CP12/03192es_ES
dc.language.isoenges_ES
dc.publisherBMJes_ES
dc.relation.urihttp://dx.doi.org/10.1136/annrheumdis-2016-210131es_ES
dc.rightsAtribución-NoComercial 3.0 Españaes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/es/*
dc.subjectEpidemiologyes_ES
dc.subjectGene polymorphismes_ES
dc.subjectKnee osteoarthritises_ES
dc.titleMitochondrial DNA haplogroups influence the risk of incident knee osteoarthritis in OAI and CHECK cohorts: a meta-analysis and functional studyes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessinfo:eu-repo/semantics/openAccesses_ES
UDC.journalTitleAnnals of the Rheumatic Diseaseses_ES
UDC.volume76es_ES
UDC.issue6es_ES
UDC.startPage1114es_ES
UDC.endPage1122es_ES


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