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

Pu Song,Gang Wang,Xiaowen Wang,Tianwen Gao,Weigang Zhang,Ling Liu,Chunying Li,Zhe Jian,Kai Li

doi:10.1111/jcmm.12874

Pu Song, Gang Wang + Show 7 more

Open Access

https://doi.org/10.1111/jcmm.12874

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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 H2O2‐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.

Highlights

Vitiligo, an acquired skin depigmentation/hypopigmentation disorder, affects 0.05–1% of the global population and approximately 0.09% of the Chinese population, independently of gender [1, 2]
nuclear factor erythroid-derived 2-like 2 (Nrf2) is a redox-sensitive transcription factor that has a protective role against oxidative stress, and Nrf2 variants may have a influential capacity for binding promoters, which undermines target gene expression [24]
This study demonstrated that whether certain genetic polymorphisms would contribute to the risk of developing vitiligo

Summary

Introduction

An acquired skin depigmentation/hypopigmentation disorder, affects 0.05–1% of the global population and approximately 0.09% of the Chinese population, independently of gender [1, 2]. Some studies have suggested that oxidative stress triggers the degeneration of basal layers of epidermal melanocytes [3, 4]. Reactive oxygen species (ROS) disrupt the homoeostasis of melanocytes and damage nucleic acids, lipids and proteins, leading to cell death [5]; for instance, excessive accumulation of H2O2 is observed in the epidermis of vitiligo patients and plays an important role in the disease [6, 7]. Accumulating lines of evidence have revealed that the nuclear factor erythroid-derived 2-like 2 (Nrf2) is a pivotal transcription factor of the antioxidant response in oxidative stress-related illnesses [8]

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