title: Keratoconus is associated with increased copy number of mitochondrial DNA.
abstract: OBJECTIVE
  To investigate the possible association of oxidative stress with keratoconus (KC), we estimated the changes in relative mitochondrial DNA (mtDNA) content.
  
  
  METHODS
  The study included 119 patients with KC and 208 controls matched for gender, ethnicity, and systemic disease status. We selected controls who were older than the patients since the mtDNA copy number tends to increase with age. The age mean (standard deviation) was 26.4(7.6) and 54.5(14.4) years for the patients and controls, respectively. The relative mtDNA copy number was estimated with the real-time quantitative PCR (qPCR) method using ND1 as the mtDNA gene and human globulin (HGB; also known as the cytoglobin gene, CYGB) as the reference single-copy nuclear gene.
  
  
  RESULTS
  The mean relative mtDNA content was significantly higher in patients with KC (1.20±0.45) than in the normal control subjects (1.04±0.36; p = 0.0004). Subjects with high mtDNA content (>1.259, i.e., greater than 75(th) percentile) were at an increased risk of the disease (odds ratio = 2.62, 95% confidence interval = 1.40 to 4.89; p =0.0025).
  
  
  CONCLUSIONS
  Increased mtDNA content in patients with KC may indicate mitochondrial respiratory chain defects and thus mitochondrial-abnormality involvement.
authors.affiliation: Ophthalmic Genetics Laboratory, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia ; Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, FL.
authors.forename: Khaled K
authors.initials: KK
authors.lastname: Abu-Amero
authors.affiliation: Ophthalmic Genetics Laboratory, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Altaf A
authors.initials: AA
authors.lastname: Kondkar
authors.affiliation: Ophthalmic Genetics Laboratory, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Taif Anwar
authors.initials: TA
authors.lastname: Azad
authors.affiliation: Ophthalmic Genetics Laboratory, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Tahira
authors.initials: T
authors.lastname: Sultan
authors.affiliation: Anterior Segment Unit, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Hatem
authors.initials: H
authors.lastname: Kalantan
authors.affiliation: Anterior Segment Unit, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Abdulrahman M
authors.initials: AM
authors.lastname: Al-Muammar
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D000078842:Cytoglobin; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D050259:Genes, Mitochondrial; D005914:Globins / Q000235:genetics; D006801:Humans; D007640:Keratoconus / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009245:NADH Dehydrogenase / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: C000627265:CYGB protein, human; D000078842:Cytoglobin; D004272:DNA, Mitochondrial; D005914:Globins; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human