8-hydroxy-2--deoxyguanosine and Vitiligo

Oxidative stress is known to be involved in the pathogenesis of autoimmune diseases such as vitiligo. Evidence suggests that the human mitochondrial DNA copy number (mtDNAcn) is vulnerable to damage mediated by oxidative stress. The purpose of this study was to examine and compare peripheral blood mtDNAcn and oxidative DNA damage byproducts (8-hydroxy-2-deoxyguanosine; 8-OHdG) in patients with vitiligo and healthy controls (HCs).. The relative mtDNAcn and the oxidative damage (formation of 8-OHdG in mtDNA) of each sample were determined by real-time quantitative PCR. Blood samples were obtained from 56 patients with vitiligo and 46 HCs.. The mean mtDNAcn and the degree of mtDNA damage were higher in patients with vitiligo than in HCs.. These data suggest that increase in mtDNAcn and oxidative DNA damage may be involved in the pathogenesis of vitiligo.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Deoxyguanosine; DNA Copy Number Variations; DNA Damage; DNA, Mitochondrial; Female; Humans; Male; Oxidative Stress; Real-Time Polymerase Chain Reaction; Vitiligo

Vitiligo is an acquired depigmentation disorder, and reactive oxygen species play an important role in melanocyte damage. Base excision repair is the major pathway responsible for removing reactive oxygen species-induced DNA damage, in which APE1, ADPRT, and XRCC1 play key roles. To investigate the association between genetic variations of these genes and the risk of vitiligo in Chinese populations, we genotyped APE1-Asp148Glu, ADPRT-Val762Ala, and XRCC1-Arg399Gln polymorphisms and measured serum 8-OHdG levels in a hospital-based case-control study. We found that a significantly increased risk of vitiligo was associated with the APE1 Asp/Glu (adjusted odds ratio (OR) 1.24; 95% confidence interval (CI) 1.02-1.52) and Glu/Glu genotypes (adjusted OR 1.48; 95% CI 1.13-1.93), compared with the APE1 Asp/Asp genotype, whereas no vitiligo risk was associated with the genotypes ADPRT-Val762Ala and XRCC1-Arg399Gln. Furthermore, serum 8-OHdG levels were elevated in the APE1-148Glu allele carriers (Asp/Glu+Glu/Glu), in an allele dose-response manner, with the risk of vitiligo (Ptrend<0.05). In addition, we found that the APE1-148Glu variant increased the 8-OHdG levels of cultured human melanocytes treated with H2O2, without any impact on the endonuclease activity. These data suggest that the APE1-Asp148Glu polymorphism aggravates oxidative stress in human melanocytes and contributes to genetic predisposition to vitiligo in Chinese people.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Cells, Cultured; China; Deoxyguanosine; DNA Damage; DNA-(Apurinic or Apyrimidinic Site) Lyase; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Hydrogen Peroxide; Melanocytes; Oxidative Stress; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; Vitiligo