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dc.contributor.authorHurtado-Roca, Yamilee 
dc.contributor.authorLedesma, Marta
dc.contributor.authorGonzalez-Lazaro, Monica 
dc.contributor.authorMoreno-Loshuertos, Raquel
dc.contributor.authorFernandez-Silva, Patricio
dc.contributor.authorEnriquez, Jose Antonio 
dc.contributor.authorLaclaustra, Martin
dc.identifier.citationPLoS One. 2016; 11(10):e0163770
dc.description.abstractAlterations of mitochondrial DNA copy number (mtDNAcn) in the blood (mitochondrial to nuclear DNA ratio) appear associated with several systemic diseases, including primary mitochondrial disorders, carcinogenesis, and hematologic diseases. Measuring mtDNAcn in DNA extracted from whole blood (WB) instead of from peripheral blood mononuclear cells or buffy coat may yield different results due to mitochondrial DNA present in platelets. The aim of this work is to quantify the contribution of platelets to mtDNAcn in whole blood [mtDNAcn(WB)] and to propose a correction formula to estimate leukocytes' mtDNAcn [mtDNAcn(L)] from mtDNAcn(WB). Blood samples from 10 healthy adults were combined with platelet-enriched plasma and saline solution to produce artificial blood preparations. Aliquots of each sample were combined with five different platelet concentrations. In 46 of these blood preparations, mtDNAcn was measured by qPCR. MtDNAcn(WB) increased 1.07 (95\% CI 0.86, 1.29; p<0.001) per 1000 platelets present in the preparation. We proved that leukocyte count should also be taken into account as mtDNAcn(WB) was inversely associated with leukocyte count; it increased 1.10 (95\% CI 0.95, 1.25, p<0.001) per unit increase of the ratio between platelet and leukocyte counts. If hematological measurements are available, subtracting 1.10 the platelets/leukocyte ratio from mtDNAcn(WB) may serve as an estimation for mtDNAcn(L). Both platelet and leukocyte counts in the sample are important sources of variation if comparing mtDNAcn among groups of patients when mtDNAcn is measured in DNA extracted from whole blood. Not taking the platelet/leukocyte ratio into account in whole blood measurements, may lead to overestimation and misclassification if interpreted as leukocytes' mtDNAcn.
dc.description.sponsorshipThis work was supported by Grants PI10/00021 and PI14/00009 (which include FEDER funding) from Institute de Salud Carlos III supported for research material; FINCyT Scienceand Technology Program (Scholarships No088-FINCyT-BDE-2014 from agreement 1663/0C-PE, between the Republic of Peru and the Inter American Development Bank) provided support in the form of salaries for author [YHR]. None of the funding institutions had any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. In addition, Yamilee Hurtado-Roca has a commercial affiliation with Boca Raton clinical Research Global Peru, which did not play a role in the study design, data collection and analysis, decision to publish, preparation of the manuscript nor provided financial support in the form of author' salaries and/or research materials.; The work of Dr. Laclaustra was supported in part by grants PI10/00021 and PI14/00009 from Instituto de Salud Carlos III, which include FEDER funding, providing funds for research material. Yamilee Hurtado-Roca was supported, in the form of salary, by FINCyT Science and Technology Program Scholarships N 088-FINCyT-BDE-2014 from agreement 1663/0C -PE, between the Republic of Peru and the Inter -American Development Bank. None of the funding institutions had any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.publisherPublic Library of Science (PLOS) 
dc.subjectCOPY NUMBER
dc.titleAdjusting MtDNA Quantification in Whole Blood for Peripheral Blood Platelet and Leukocyte Counts
dc.typejournal article
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderMinisterio de la Producción (Perú) 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.identifier.journalPLoS One
dc.repisalud.orgCNICCNIC::Grupos de investigación::Genética Funcional del Sistema de Fosforilación Oxidativa
dc.repisalud.orgCNICCNIC::Grupos de investigación::Imagen Cardiovascular y Estudios Poblacionales
dc.rights.accessRightsopen accesses_ES

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