title: Mitochondrial DNA damage is associated with damage accrual and disease duration in patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  To determine the extent of mitochondrial DNA (mtDNA) damage in systemic lupus erythematosus (SLE) patients compared to healthy subjects and to determine the factors associated with mtDNA damage among SLE patients.
  
  
  METHODS
  A cross-sectional study was performed in 86 SLE patients (per American College of Rheumatology classification criteria) and 86 healthy individuals matched for age and gender. Peripheral blood mononuclear cells (PBMCs) were collected from subjects to assess the relative amounts of mtDNA damage. Quantitative polymerase chain reaction assay was used to measure the frequency of mtDNA lesions and mtDNA abundance. Socioeconomic-demographic features, clinical manifestations, pharmacologic treatment, disease activity, and damage accrual were determined. Statistical analyses were performed using t test, pairwise correlation, and Pearson's chi-square test (or Fisher's exact test) as appropriate.
  
  
  RESULTS
  Among SLE patients, 93.0% were women. The mean (SD) age was 38.0 (10.4) years and the mean (SD) disease duration was 8.7 (7.5) years. SLE patients exhibited increased levels of mtDNA damage as shown by higher levels of mtDNA lesions and decreased mtDNA abundance as compared to healthy individuals. There was a negative correlation between disease damage and mtDNA abundance and a positive correlation between mtDNA lesions and disease duration. No association was found between disease activity and mtDNA damage.
  
  
  CONCLUSIONS
  PBMCs from SLE patients exhibited more mtDNA damage compared to healthy subjects. Higher levels of mtDNA damage were observed among SLE patients with major organ involvement and damage accrual. These results suggest that mtDNA damage have a potential role in the pathogenesis of SLE.
authors.affiliation: Department of Medicine (Division of Rheumatology), University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: L
authors.initials: L
authors.lastname: López-López
authors.affiliation: Puerto Rico Clinical and Translational Research Consortium, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico School of Medicine, Institute for Clinical Research Education, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: M
authors.initials: M
authors.lastname: Nieves-Plaza
authors.affiliation: Department of Pharmacology and Toxicology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: M del R
authors.initials: Mdel R
authors.lastname: Castro
authors.affiliation: Department of Medicine (Division of Rheumatology), University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Y M
authors.initials: YM
authors.lastname: Font
authors.affiliation: Department of Physiology and Biophysics, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: C A
authors.initials: CA
authors.lastname: Torres-Ramos
authors.affiliation: Department of Medicine (Division of Rheumatology), University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: L M
authors.initials: LM
authors.lastname: Vilá
authors.affiliation: Department of Pharmacology and Toxicology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico sylvette.ayala@upr.edu.
authors.forename: S
authors.initials: S
authors.lastname: Ayala-Peña
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D004272:DNA, Mitochondrial
keywords: Systemic lupus erythematosus; disease activity; disease damage; mitochondrial DNA; mitochondrial dysfunction; oxidative stress