Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations

J Cell Mol Med. 2016 Oct;20(10):1840-50. doi: 10.1111/jcmm.12874. Epub 2016 May 25.


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.

Keywords: Nrf2; SNP; vitiligo.

MeSH terms

  • Asian People / genetics*
  • Base Sequence
  • Case-Control Studies
  • Cell Line
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Glutathione Transferase / metabolism
  • Heme Oxygenase-1 / genetics
  • Humans
  • Logistic Models
  • Male
  • NF-E2-Related Factor 2 / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic*
  • Risk Factors
  • Transcription, Genetic
  • Vitiligo / genetics*


  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Heme Oxygenase-1
  • Glutathione Transferase