Keratoconus is associated with increased copy number of mitochondrial DNA

Purpose: 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 75th 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.