Open AccessGenetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations
Author(s) -
Song Pu,
Li Kai,
Liu Ling,
Wang Xiaowen,
Jian Zhe,
Zhang Weigang,
Wang Gang,
Li Chunying,
Gao Tianwen
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12874
Subject(s) - vitiligo , genotype , allele , odds ratio , heme oxygenase , oxidative stress , promoter , biology , restriction fragment length polymorphism , microbiology and biotechnology , genetics , medicine , gene , heme , endocrinology , enzyme , gene expression , biochemistry
The nuclear factor erythroid‐derived two‐like 2‐antioxidant response element (Nrf2‐ ARE ) pathway and its downstream antioxidant enzyme heme oxygenase‐1 ( HMOX 1 or HO ‐1) play essential roles in H 2 O 2 ‐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 ( P trend < 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.