Genetic variants of the APE1 gene and the risk of vitiligo in a Chinese population: a genotype-phenotype correlation study.
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.
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Chao
C
Wei
Zhe
Z
Jian
Lin
L
Wang
Huini
H
Qiang
Qiong
Q
Shi
Sen
S
Guo
Kai
K
Li
Ye
Y
Huang
Ling
L
Liu
Qiang
Q
Li
Qi
Q
Luan
Xiuli
X
Yi
Xia
X
Li
Gang
G
Wang
Tianwen
T
Gao
Chunying
C
Li
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002478:Cells, Cultured; D002681:China; D004249:DNA Damage / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000097:blood; D014820:Vitiligo / Q000097:blood / Q000235:genetics*
D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D003849:Deoxyguanosine