Dataset Information

Mitochondrial DNA copy number in affected and unaffected LHON mutation carriers.

ABSTRACT: OBJECTIVES:Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease characterized by a variable and reduced penetrance. Individuals carrying a primary LHON-causing mitochondrial DNA (mtDNA) mutation may either remain asymptomatic lifelong, as unaffected carriers, or develop sudden central visual loss that rapidly aggravates over some weeks. Over the years several genetic/environmental triggers able to modulate the risk of developing LHON have been proposed. We provided data supporting a possible correlation between LHON penetrance and the mtDNA copy number, a raw index of mitochondrial mass, whose increase could represent a compensatory response that cells implement to alleviate the pathogenic effect of the primary LHON-causing mtDNA mutations. DATA DESCRIPTION:We collected Italian and Spanish subjects harboring one of the three common LHON primary mutations, either in heteroplasmic or homoplasmic status. For each population we were able to discriminate between affected subjects presenting typical clinical tracts of LHON and LHON-causing mutation carriers showing no symptoms correlated with vision loss. Each subject has been characterized for the presence of a LHON primary mutation, for its status of homoplasmy or heteroplasmy, and for the mtDNA content per cell, expressed as relative mtDNA/nDNA ratio respect to controls. Additional clinical information is present for all the Italian subjects.

SUBMITTER: Bianco A

PROVIDER: S-EPMC6302380 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Mitochondrial DNA copy number in affected and unaffected LHON mutation carriers.

Bianco Angelica A Valletti Alessio A Longo Giovanna G Bisceglia Luigi L Montoya Julio J Emperador Sonia S Guerriero Silvana S Petruzzella Vittoria V

BMC research notes 20181220 1

<h4>Objectives</h4>Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease characterized by a variable and reduced penetrance. Individuals carrying a primary LHON-causing mitochondrial DNA (mtDNA) mutation may either remain asymptomatic lifelong, as unaffected carriers, or develop sudden central visual loss that rapidly aggravates over some weeks. Over the years several genetic/environmental triggers able to modulate the risk of developing LHON have been proposed. We provid ...[more]

PMID: 30572950

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Project description:ImportanceMitochondrial dysfunction is a core component of the aging process and may play a key role in atherosclerotic cardiovascular disease. Mitochondrial DNA copy number (mtDNA-CN), which represents the number of mitochondria per cell and number of mitochondrial genomes per mitochondrion, is an indirect biomarker of mitochondrial function.ObjectiveTo determine whether mtDNA-CN, measured in an easily accessible tissue (buffy coat/circulating leukocytes), can improve risk classification for cardiovascular disease (CVD) and help guide initiation of statin therapy for primary prevention of CVD.Design, setting, and participantsProspective, population-based cohort analysis including 21?870 participants (20?163 free from CVD at baseline) from 3 studies: Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities Study (ARIC), and Multiethnic Study of Atherosclerosis (MESA). The mean follow-up was 13.5 years. The study included 11?153 participants from ARIC, 4830 from CHS, and 5887 from MESA. Analysis of the data was conducted from March 10, 2014, to January 29, 2017.ExposuresMitochondrial DNA-CN measured from buffy coat/circulating leukocytes.Main outcomes and measuresIncident CVD, which combines coronary heart disease, defined as the first incident myocardial infarction or death owing to coronary heart disease, and stroke, defined as the first nonfatal stroke or death owing to stroke.ResultsOf the 21?870 participants, the mean age was 62.4 years (ARIC, 57.9 years; MESA, 62.4 years; and CHS, 72.5 years), and 54.7% of participants were women. The hazard ratios for incident coronary heart disease, stroke, and CVD associated with a 1-SD decrease in mtDNA-CN were 1.29 (95% CI, 1.24-1.33), 1.11 (95% CI, 1.06-1.16), and 1.23 (95% CI, 1.19-1.26). The associations persisted after adjustment for traditional CVD risk factors. Addition of mtDNA-CN to the 2013 American College of Cardiology/American Heart Association Pooled Cohorts Equations for estimating 10-year hard atherosclerosis CVD risk was associated with improved risk classification (continuous net reclassification index, 0.194; 95% CI, 0.130-0.258; P?<?.001). Mitochondrial DNA-CN further improved sensitivity and specificity for the 2013 American College of Cardiology/American Heart Association recommendations on initiating statin therapy for primary prevention of ASCVD (net 221 individuals appropriately downclassified and net 15 individuals appropriately upclassified).Conclusions and relevanceMitochondrial DNA-CN was independently associated with incident CVD in 3 large prospective studies and may have potential clinical utility in improving CVD risk classification.

Dataset Information

Mitochondrial DNA copy number in affected and unaffected LHON mutation carriers.

Publications

Mitochondrial DNA copy number in affected and unaffected LHON mutation carriers.

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