title: Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations.
abstract: The nuclear factor erythroid-derived two-like 2-antioxidant response element (Nrf2-ARE) pathway and its downstream antioxidant enzyme heme oxygenase-1 (HMOX1 or HO-1) play essential roles in H2 O2 -induced oxidative damage in human melanocytes. However, the link between Nrf2 promoter polymorphisms and susceptibility to oxidative stress-related diseases such as vitiligo is unknown. This study evaluated the association of the Nrf2 and HO-1 genes polymorphisms with vitiligo susceptibility. In this case-control study of 1136 Han Chinese vitiligo patients and 1200 controls, Nrf2 (rs35652124 and rs6721961) and HO-1 (rs2071746) genes were genotyped by PCR-restriction fragment length polymorphism analysis. Overall, a significantly decreased risk of vitiligo was found to be associated with Nrf2 rs35652124 CC and combined (CT+CC) genotypes [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.50-0.83 and OR, 0.84, 95% CI 0.71-0.99, respectively], as well as among subgroups: female, onset age ≤20 and never smoker. We subsequently found that Nrf2 rs35652124 C allele had higher transcriptional activity in the luciferase reporter assay compared with Nrf2 rs35652124 T allele. Furthermore, we investigated serum HO-1 activity was associated with the rs35652124 CT+CC genotype and lower in patients than in controls (P = 0.024). Logistic regression analysis showed a dose-response relationship between lower vitiligo risk and increased HO-1 activity in rs35652124 CT+CC genotype carriers (Ptrend < 0.05). These findings indicate that the C allele of rs35652124 located in the promoter region of Nrf2 gene is associated with protective effect on vitiligo in a Han Chinese population.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Song
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jian
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Weigang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. lichying@fmmu.edu.cn.
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. gaotw75401@hotmail.com.
authors.forename: Tianwen
authors.initials: T
authors.lastname: Gao
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D014158:Transcription, Genetic; D014820:Vitiligo / Q000235:genetics*
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D051547:Heme Oxygenase-1; D005982:Glutathione Transferase
keywords: Nrf2; SNP; vitiligo