Genetic variants of the APE1 gene and the risk of vitiligo in a Chinese population: A genotype-phenotype correlation study

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• 作者：Chao Wei¹ ; Zhe Jian¹ ; Lin Wang¹ ; Huini Qiang ; Qiong Shi ; Sen Guo ; Kai Li ; Ye Huang ; Ling Liu ; Qiang Li ; Qi Luan ; Xiuli Yi ; Xia Li ; Gang Wang ; Tianwen Gao ; ^{gaotw@fmmu.edu.cn} ; Chunying Li ; ^{lichying@fmmu.edu.cn}
• 关键词：ADPRT ; adenosine diphosphate ribosyl transferase ; APE1 ; apurinic/apyrimidinic endonuclease 1 ; BER ; base excision repair ; ROS ; reactive oxygen species ; SNP ; single-nucleotide polymorphism ; XRCC1 ; X-ray repair cross-complementing group 1 ; 8-OHdG ; 8-hydroxy-
• 刊名：Free Radical Biology and Medicine
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：58
• 期：Complete
• 页码：64-72
• 全文大小：798 K

文摘

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 (P_trend<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.