Variability of oxidative stress‐related genes in keratoconus and Fuchs endothelial corneal dystrophy

Abstract

AbstractPurpose In the present work we investigated polymorphism in nuclear genes encoding proteins important for the cellular reaction to oxidative stress and mutations in mitochondrial DNA in two eye diseases with established role of oxidative stress in their pathology: keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD).Methods Over 200 FECD and KC patients as well as more than 300 sex‐ and age‐matched controls were enrolled in this study. Genetic variation in nuclear DNA was determined in peripheral blood lymphocytes by allele‐specific and restriction length fragment polymorphism PCR. Quantitative real‐time PCR with TaqMan probes was employed to study mutagenesis in mitochondrial DNA (mtDNA).Results Genotypes of polymorphisms of genes encoding catalase and superoxide dismutase, glutathione transferase, enzymes neutralizing reactive oxygen species, were associated with the increased risk of AMD, FECD and KC. Polymorphism of numerous DNA repair genes, including hOGG1, MUTYH, UNG and SMUG1 was associated with AMD and KC. Finally, we found some associations between the occurrence of FECD and mtDNA mutagenesis, expressed by the number of mtDNA copies and specific deletions and point mutations, including 4977 bp deletion in mtDNA encoding 5 tRNAs and 7 proteins of respiratory chain as well as the 414T>G transversion.Conclusion Polymorphism in nuclear genes encoding oxidative stress‐related proteins and mutations in mitochondrial DNA may contribute to the risk of occurrence and development of KC and FECD by modulating the cellular reaction to the stress.