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

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 H(2)O(2)‐induced oxidative damage in human melanocytes. However, the link between Nrf2 promoter polymorphisms...

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Autores principales: Song, Pu, Li, Kai, Liu, Ling, Wang, Xiaowen, Jian, Zhe, Zhang, Weigang, Wang, Gang, Li, Chunying, Gao, Tianwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020638/
https://www.ncbi.nlm.nih.gov/pubmed/27222475
http://dx.doi.org/10.1111/jcmm.12874
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author Song, Pu
Li, Kai
Liu, Ling
Wang, Xiaowen
Jian, Zhe
Zhang, Weigang
Wang, Gang
Li, Chunying
Gao, Tianwen
author_facet Song, Pu
Li, Kai
Liu, Ling
Wang, Xiaowen
Jian, Zhe
Zhang, Weigang
Wang, Gang
Li, Chunying
Gao, Tianwen
author_sort Song, Pu
collection PubMed
description 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 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.
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spelling pubmed-50206382016-10-01 Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations Song, Pu Li, Kai Liu, Ling Wang, Xiaowen Jian, Zhe Zhang, Weigang Wang, Gang Li, Chunying Gao, Tianwen J Cell Mol Med Original Articles 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 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. John Wiley and Sons Inc. 2016-05-25 2016-10 /pmc/articles/PMC5020638/ /pubmed/27222475 http://dx.doi.org/10.1111/jcmm.12874 Text en © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Song, Pu
Li, Kai
Liu, Ling
Wang, Xiaowen
Jian, Zhe
Zhang, Weigang
Wang, Gang
Li, Chunying
Gao, Tianwen
Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations
title Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations
title_full Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations
title_fullStr Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations
title_full_unstemmed Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations
title_short Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations
title_sort genetic polymorphism of the nrf2 promoter region is associated with vitiligo risk in han chinese populations
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020638/
https://www.ncbi.nlm.nih.gov/pubmed/27222475
http://dx.doi.org/10.1111/jcmm.12874
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